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Epigenome-wide analysis reveals functional modulators of drug sensitivity and post-treatment survival in chronic lymphocytic leukaemia
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Abstract<sec> <title>Background

Chronic lymphocytic leukaemia (CLL) patients display a highly variable clinical course, with progressive acquisition of drug resistance. We sought to identify aberrant epigenetic traits that are enriched following exposure to treatment that could impact patient response to therapy.

Methods

Epigenome-wide analysis of DNA methylation was performed for 20 patients at two timepoints during treatment. The prognostic significance of differentially methylated regions (DMRs) was assessed in independent cohorts of 139 and 163 patients. Their functional role in drug sensitivity was assessed in vitro.

Results

We identified 490 DMRs following exposure to therapy, of which 31 were CLL-specific and independent of changes occurring in normal B-cell development. Seventeen DMR-associated genes were identified as differentially expressed following treatment in an independent cohort. Methylation of the HOXA4, MAFB and SLCO3A1 DMRs was associated with post-treatment patient survival, with HOXA4 displaying the strongest association. Re-expression of HOXA4 in cell lines and primary CLL cells significantly increased apoptosis in response to treatment with fludarabine, ibrutinib and idelalisib.

Conclusion

Our study demonstrates enrichment for multiple CLL-specific epigenetic traits in response to chemotherapy that predict patient outcomes, and particularly implicate epigenetic silencing of HOXA4 in reducing the sensitivity of CLL cells to therapy.

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Publication Date
Sun Dec 04 2016
Journal Name
Baghdad Science Journal
Effect of the Clenbuterol drug in some physiological parameters in male rabbits(Oryctolagus cuniculs)
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This study was designed to investigate the effect of the Clenbuterol drug in some physiological parameters of Liver, Kidney function and lipidprofie concentration. Fourty adult male rabbits were used in this study. The animals were randomly divided into four groups,the first group was given distilled water (control) ,while the other third groups were given (2,4,6 µg/kg) of Clenbuterol drug for 30 days. Blood samples were collected after 14 and 30 days of the treatment for biochemical study. Drug caused non significant increase(P<0.05)in the AST and ALT enzymeactivity in second and third groups during treatment period ,while we note a significant increase(P<0.05) in both AST,ALT enzyme level in fourth group compared with control group , as

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Publication Date
Wed Sep 14 2016
Journal Name
Journal Of Baghdad College Of Dentistry
Assessment of Alkaline Phosphatase, Salivary Flow Rate and Salivary Potential of Hydrogen in Relation to Severity of Chronic Periodontitis
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Background: The cells of periodontium contain many intracellular enzymes like (alkaline phosphatase ALP) that are released outside into the saliva and gingival crevicular fluid (GCF) after destruction of periodontal tissue. The aim of study was to determine the activity of this enzyme in saliva and its relation to the salivary flow rate, PH and clinical periodontal parameters in patients with chronic periodontitis. Subject, Materials and methods: Sample population consist of 75 individuals ;divided into four groups , the first group (15):control subject, the second group (20):mild chronic periodontitis, the third group(20) moderate chronic periodontitis and the fourth group (20) sever chronic periodontitis, Measurements of plaque index (PL

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Publication Date
Thu Sep 01 2016
Journal Name
Journal Of Baghdad College Of Dentistry
Assessment of alkaline phosphatase, salivary flow rate and salivary potential of hydrogen in relation to severity of chronic periodontitis
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Publication Date
Sun Sep 07 2014
Journal Name
Baghdad Science Journal
Effect of Aspirin drug in Liver tissue of swiss white mice Mus musculus
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This study was designed to identify the extent of the effect of drug Acetylsalicylic acid (aspirin) on histological structure of liver in Swiss albino mice Mus musculus.(16) mice were used and divided into two groups. The first groupwas orally treated with )0.5ml(of aspirinat concentration of (50 mcg / kg) and the second group was considered as control group Treated with distiled water lasted for 30 days. Treatment with Aspirin led to the occurrence of histopathological cases included liver necrosis ,cellular infilitration, congestion in central vein and a case of Hemorrhage. The results also showed the absence of radial arrangement of the constituents of hepatic cells from tissue due to these changes with the control group.

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Publication Date
Thu Mar 30 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
The Effect of Chronic Renal Failure on Thyroid Hormones
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       Chronic renal failure (CRF) affects thyroid function in multiple ways, including low circulating thyroid hormone concentration, altered peripheral hormone metabolism, disturbed binding to carrier proteins, possible reduction in tissue thyroid hormone content, and increased iodine store in thyroid glands.The target of study is to find a relationship between chronic renal failure and thyroid function.In addition, we tried to study the effect of CRF on serum creatinine dependent on the level of thyroid hormones (T3 and T4) and thyroid stimulating hormones(TSH). Forty patients with chronic renal failure (20 male, 20 female) were enrolled in this study in addition to forty healthy individual as control gro

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Publication Date
Tue Aug 23 2022
Journal Name
International Journal Of Health Sciences
Correlation between paraoxonase-1 arylesterase activities and clopidogrel drug in patients with coronary artery disease
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Background: Coronary artery disease (CAD) is one of the leading causes of death worldwide. Clopidogrel, antiplatelet drug, has been widely used for management of CAD. Arylesterase, the activity of Paraoxonase-1 (PON-1), is mainly contributed in the biotransformation of clopidogrel to its active thiol form. The purpose of this study was to investigate the effect of receiving clopidogrel drug on the arylesterase activities in CAD patients. The effect of receiving clopidogrel drug on the antioxidant activity of arylesterase was also monitored by determination of malondialdehyde (MDA) level. Methods: One hundred CAD patients, who were followed-up for 5 days after reciving clopidogrel, and 50 healthy volunteers were included in our study

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Publication Date
Thu Feb 07 2019
Journal Name
Journal Of The College Of Education For Women
Search for Identity in Michael Ondaatje's Post colonial Novel In the Skin of a Lion
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In his post colonial novel, In the Skin of a lion, the Canadian/Sri Lankan writer,
Michael Ondaatje is so interested in the term "Post colonialism" because he wants to show
that the term doesn't only refer to a period of time that comes after colonialism. In other
words, post colonialism is not only referred to as a literal description of formerly colonial
societies. He deals with the termas a literary genre and an academic construct that describes
the global conditions of a man after a period of colonialism. He shows that post colonialism is
a theory that tries to examine and explore the different styles and faces of European authority
to control the colonized. Ondaatje's attempt through such term is to unmask Europ

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Publication Date
Sat Jul 01 2017
Journal Name
Journal Of Biological Chemistry
Functional and phylogenetic evidence of a bacterial origin for the first enzyme in sphingolipid biosynthesis in a phylum of eukaryotic protozoan parasites
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Publication Date
Fri Jun 30 2017
Journal Name
Journal Of Madenat Al-elem University College
Study the toxic effect of the herbicide Gold topik (80EC) on survival and behavior of mosquito fish (Gambusia holbrooki Girard 1859)
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Publication Date
Tue Jun 02 2026
Journal Name
Journal Of Baghdad College Of Dentistry
Assessment of some salivary enzymes levels in type 2 diabetic patients with chronic periodontitis (Clinical and biochemical study)
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Background: Diabetic patients have been reported to be more susceptible to gingivitis and periodontitis than healthy subjects. Many intracellular enzymes like (alkaline phosphatase- (ALP), aspartate aminotransferase- (AST) and alanine aminotransferase- (ALT) that are released outside cells into the gingival crevicular fluid (GCF) and saliva after destruction of periodontal tissue during periodontitis. This study was conducted to determine the periodontal health status and the levels of salivary enzymes (ALP, AST and ALT) of the study and control groups and to correlate the levels of these enzymes with clinical periodontal parameters in each study group. Subjects, Materials and Methods: One hundred subjects were enrolled in the study, with a

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