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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
Fri Nov 11 2022
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
Analytical Methods for Determination of Ketoprofen Drug: A review
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Ketoprofen has recently been proven to offer therapeutic potential in preventing cancers such as colorectal and lung tumors, as well as in treating neurological illnesses. The goal of this review is to show the methods that have been used for determining ketoprofen in pharmaceutical formulations. Precision product quality control is crucial to confirm the composition of the drugs in pharmaceutical use. Several analytical techniques, including chromatographic and spectroscopic methods, have been used for determining ketoprofen in different sample forms such as a tablet, capsule, ampoule, gel, and human plasma. The limit of detection of ketoprofen was 0.1 ng/ ml using liquid chromatography with tandem mass spectrometry, while it was 0

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Publication Date
Sat Jan 02 2016
Journal Name
Iraq Nat J Chem
Adsorption study of drug cefixime onto surface Iraqi Attapulgite
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Publication Date
Wed Nov 04 2015
Journal Name
Journal Of Chemical, Biological And Physical Sciences
The Effect of Alkaloid Extracted from Cordia myxa Leaves on the Survival of Mustard Aphid Lipaphis erysimi (Kalt.)
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Publication Date
Thu Sep 30 2021
Journal Name
International Journal Of Research In Social Sciences And Humanities
The Anonymous Identity of Forced Migrants: A Post-Colonial Study
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Colonialism invades the Third World countries, physically and psychologically. This article exposes but sample of the physical and psychological consequences of colonialism. The Beekeeper of Aleppo (2019) by the British novelist, Christy Lefteri is a typical novel to diagnose the harsh circumstances of individuals within and after the disaster. Since it depicts characters from Asian countries, it would be a best representative for all Asian people who suffer colonialism. Migration toward anonymity is the mere option for the colonized people. Aftermath, they experience displacement, trauma, and the loss of identity.

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Publication Date
Mon Jan 01 2007
Journal Name
Iraqi Postgraduate Medical Journal
Therapeutic evaluation of spironolactone and finasteride in the treatment of acne vulgaris
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S Khalifa E, AM Sabeeh A, AN Adil A, AW Ghassan H…, 2007

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Publication Date
Thu Jan 07 2021
Journal Name
Indian Journal Of Forensic Medicine &amp; Toxicology
Efficacy and Safety of Sacral Neuromodulation in Treatment of Refractory Overactive Bladder
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Publication Date
Sun Oct 07 2018
Journal Name
Al-kindy College Medical Journal
Risedronate as a therapeutic trial post-hysterectomy in premenopausal women to prevent osteoporosis
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Background: Osteoporosis is a skeletal defect manifested by a reduction of bone strength as a result of reduced bone mass to the extent that there is a higher risk of fracture even on minor trauma. Hysterectomy in a premenopausal woman is a well known cause of ovarian failure resulting in an increased risk of osteoporosis.

Objective : To clarify bisphosphonate's preventive effect on osteopenia and osteoporosis in premenopausal women after hysterectomy.

Type of the study: Cross –sectional study.

Method:  84 premenopausal females post hysterectomy aged between 40 – 50 years, were enrolled in this randomized controlled double blinded trail a

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Publication Date
Tue Jun 30 2015
Journal Name
Al-kindy College Medical Journal
Major inflammatory patterns of chronic sinonasal diseases and their accompanied anatomical variations; CT scan review
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Background: Because of wide use of Functional Endoscopic Sinus Surgery (FESS) technique in the recent years and basic role of coronal computed tomography (CT) scan in demonstrating the normal drainage route of para-nasal sinuses, identifying the major patterns of inflammatory sinonasal disease and accompanied anatomical variations is essential for appropriate preoperative surgical planning. In review of publisthed literature, there is no data on CT patterns of chronic inflammatory sinonasal disease and their accompained anatomical variations of nose and PNS in our local population.Objectives: was to determine the frequency of CT patterns and variations in patients with sinonasal symptoms.Methods: This was a cross sectional descriptive st

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Publication Date
Thu Jun 30 2011
Journal Name
Al-kindy College Medical Journal
Prevalence of clinically significant Hepatopulmonary Syndrome among Patients with Chronic Liver Disease and Portal Hypertension
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Background : The hepatopulmonary syndrome (HPS) is defined as the triad of liver disease, arterial deoxygenation, and pulmonary vascular dilatation. The reported prevalence of HPS in cirrhotic patients varies between 5% -17.5%.Objective : To estimate the prevalence of hepatopulmonary syndrome among patients with chronic liver disease and portal hypertension and to study the correlation between HPS and the severity of liver disease.Patients and methods : Thirty patients were studied for the presence of HPS using transthoracic contrast echocardiography for detection of pulmonary vasodilatation. Arterial oxygen saturation (SaO2) was determined in erect and supine position using a pulse oximeter , (SaO2 ≤ 92 % in supine position and/or a d

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Publication Date
Thu Nov 08 2018
Journal Name
Iraqi National Journal Of Nursing Specialties
Health- related quality of life for adult patient with chronic viral hepatitis B and C
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Objective(s): This study aims to assess health related quality of life among Iraqi patients with chronic viral hepatitis
B and C also to find out the relationship between health related quality of life and patients demographic
characteristic and to design a new measurement scale for assessing QoL among viral hepatitis B and C patients
which can be suitable to be adopted for Iraqi patients
Methodology: A descriptive quantitative study is carried out at Gastroenterology and Hepatology Teaching
Hospital from February, 1st, 2011 to August 30th 2011, Anon probability (purposive sample) of (100) chronic viral
hepatitis B and C persons , who were clients of Gastroenterology and Hepatology Teaching Hospital / outpatient
clin

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