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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
Mon Jul 01 2024
Journal Name
Journal Of The Faculty Of Medicine Baghdad
The Burden of Chronic Obstructive Pulmonary Disease COPD in Stable Patients and its Association with Inflammatory Biomarkers and Body Mass Index
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Background: Chronic obstructive pulmonary disease (COPD) is a progressive airflow limitation that is preventable but not curable. It is associated with persistent symptoms that cause a considerable burden on individual productivity at work, and daily activities, and reduced quality of life, also burdening the healthcare system and society. Objectives: The study aims to measure the burden of COPD on patients in terms of daily activities and work productivity. It also seeks to investigate some inflammatory biomarkers' levels and their correlation with selected outcomes. Patients and Methods: A cross-sectional study on 120 stable COPD patients who were diagnosed and treated according to the GOLD guidelines at Kirkuk General Hospital's

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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
Wed Jul 01 2020
Journal Name
International Journal Of Drug Delivery Technology
Gold nanoparticle: Synthesis, functionalization, enhancement, drug delivery and therapy: A review
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Publication Date
Fri Sep 01 2017
Journal Name
Iosr Journal Of Pharmacy And Biological Sciences(iosr-jpbs)
Histopathological study in the spleen of Albino Mice treated with glucosamine sulfate drug
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Publication Date
Wed Dec 12 2018
Journal Name
International Journal Of Pharmaceutical Research
Effect of Carbamazepine Drug on Liver Ultrastructure in Female White Mice (Mus musculus)
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Epilepsy is the most common neurological disorder after Alzheimer and other cerebrovascular diseases. Antiepileptic drugs (AED's) are one of the most important methods to prevent epileptic seizers. Antiepileptic drugs can cause damage to the liver which is the largest and most important glandular organ in the body with many other drugs. Carbamazepine (CBZ) is a known anticonvulsant that is widely used and known for a decade, it was used to treat trigeminal neuralgia, bipolar disorder and epilepsy and it can cause hepatotoxicity. In this study female white mice received CBZ suspension at a dose of 20 mg/kg/mouse via gastric gavage for 30 days, tissue samples were collected for scanning electron microscopy. We observed the adverse effects of

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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
Wed Jun 30 2010
Journal Name
Al-kindy College Medical Journal
Manifestation and response of Laryngopharygeal reflux to treatment in Kurdistan -IRAQ
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BACKGROUND: In 1972 complete description of the
inflammation of posterior third of the vocal cords was
done, with barium swallow confirming Gastro
Esophageal Disease [CRED] & subsequent successful
symptomatic treatment with antacid. The possible
association between GERD & chronic laryngitis was
initially known as acid laryngitis .2
*from the Department of ENT, Hawlear Medical College, Hawlear university. Department of ENT, Rezgary Teaching Hospital, Erbil.
Correspondence to :
Dr.Said Mustafa Said
Corespondence Address to : Dr.Said Mustafa Said _ E- mail: Email [email protected] Mob. 07504563829
Recived at : 15 th Dec 2009 Accepted at : 3ed Nov 2010

OBJECTIVE: To record the common presentat

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Publication Date
Sun Apr 06 2014
Journal Name
Journal Of Educational And Psychological Researches
The reality of child labor in Baghdad ... And access to treatment
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  The phenomenon of child labor, any activity performed by a child and represents a contribution to the production, this phenomenon had been rife in Iraqi society, after that the proportion of child labor for the age group (6-14 years) amounting to 3% in 2006, became for  the same age group of 8% in 2008*.                                                      

It is recognized that each phenomenon reasons, the phenomenon which our atten

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Publication Date
Thu Jun 18 2015
Journal Name
Journal Of Kerbala University
Effect of Carbamazepine drug on formation of decidual tissue in femal of Mus musculus
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Implantation of blastocyst is considered as a sensitive process in the life of growing embryo. Thus this critical period could be under threat from the harmful effect of many drugs ,among them is the carbamazepine which is used by many women for a treatment of epilepsy . The present experiment was designed to study the effect of this drug on the process of implantation ;especially during the days 7 and 9 of pregnancy. For those purpose 169 pregnant albino mice, of 25 gm weight for each one, were used .The mice were divided into control group given orally normal saline, and treated group given orally carbamazepine with concentration of 15 mg\kg. Samples from pregnant uteri containing the embryos were used. They were first fixed in Boun's sol

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Publication Date
Tue Aug 01 2023
Journal Name
Biochemical And Cellular Archives
Interleukin-32(IL-32) gene expression in Iraqi chronic hepatitis B virus patients
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Hepatitis B infection is a prominent infectious disease caused by hepatitis B virus (HBV), which infect liver and is considered as the main cause of liver cirrhosis, fibrosis and liver cancer worldwide. A pro-inflammatory cytokine Interleukin32 is believed to have a role in chronic HBV infections. Since its role in CHB infections is remain unclear, this study was done to detect IL-32 gene expression in CHB patients in order to identify its exact role. A total number of 110 blood samples were collected from Gastroenterology and Hepatology Teaching Hospital in Baghdad Medical City from CHB patients for both males and females with different age groups according to the research ethics form then sent to Central Public Health Laboratory (CPHL),

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