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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
Tue Jun 16 2020
Journal Name
Frontiers In Pharmacology
Administration of Δ9‐Tetrahydrocannabinol (THC) Post‐Staphylococcal Enterotoxin B Exposure Protects Mice From Acute Respiratory Distress Syndrome and Toxicity
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Publication Date
Fri Dec 23 2022
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Aspirin Derivatives Exploration: A Review on Comparison Study with Parent Drug
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In recent decades, drug modification is no longer unusual in the pharmaceutical world as living things are evolving in response to environmental changes. A non-steroidal anti-inflammatory drug (NSAID) such as aspirin is a common over-the-counter drug that can be purchased without medical prescription. Aspirin can inhibit the synthesis of prostaglandin by blocking the cyclooxygenase (COX) which contributes to its properties such as anti-inflammatory, antipyretic, antiplatelet and etc. It is also being considered as a chemopreventive agent due to its antithrombotic actions through the COX’s inhibition. However, the prolonged use of aspirin can cause heartburn, ulceration, and gastro-toxicity in children and adults. This review article hi

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Publication Date
Mon Jan 01 2018
Journal Name
Iraqi Journal Of Embryos & Infertility Researches
Analysis of Amino Acids of the Brain in Embryo and Adult of Quail.
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Amino acids have the role in the process of proteins synthesis. They are an essential source of nitrogen atoms that have a role in the pathways of synthetic reaction pathways. The carbon skeletons of the amino acids are the source of energy in addition to their role as precursors in the paths of interactions. The amino acids analysis for the brain of the quail bird in different stage of development (10-16 days of incubation) in addition to the hatching stage (17th day) and the adult. Materials and Methods: Amino Acids Analysis The amino acids were separated from the embryos and adult brains of the quail bird Coturnix coturnix and were diagnosed based on standard amino acids, using high performance liquid chromatographic device (H.P.L.C.). R

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Publication Date
Sun Oct 01 2017
Journal Name
Journal Of Economics And Administrative Sciences
Analysis of the relationship between modernity and economic development Analysis of the relationship between modernity and economic development
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This research shows the problem of the economic development of underdeveloped countries in an unconventional way, as these papers explain the problems of the economic development. This research not only reviews the problems, but it illustrates them in a philosophical way, basis of the data of modernity, this mean it is a process of connecting between the absence of the modernity values and the failure of development in underdeveloped countries. The Search follows the descriptive approach to get to the goal of search by four main axes. The first axis includes clarifying  modernity and its principles, the second axis includes clarifying the economic development , the third axis includes the features of the mod

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Publication Date
Sun Dec 01 2013
Journal Name
The Iraqi Postgraduate Medical Journal
Comparative Study Between Glimepiride and Glibenclamide in the Treatment of Type 2 Diabetic Patients in Al-Yarmouk Hospital
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Comparative Study Between Glimepiride and Glibenclamide in the Treatment of Type 2 Diabetic Patients in Al-Yarmouk Hospital

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Publication Date
Fri Jun 17 2016
Journal Name
International Journal Of Humanities And Cultural Studies
Defying Post Colonialism: the Quest for Cultural Adaptation and Transcultural Identity with References to Some Postcolonial Novels
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Postcolonial reading for any text aroused a great controversy that deserves to be studied it give more dimensions with the awareness that it can be interpreted in numerous ways. Postcolonialism is a challenging field as it covers variety of political, psychological, cultural, and economical activities often called ‘postcolonial’. The concept of culture worked effectively in shaping and mapping postcolonial struggles, which have so profoundly reshaped our world. Man's sense of cultural displacement is the core of this project. Man's quest for cultural adaptation forms a kind of equilibrium and compromise to the vision of human liberation. It is very important to minimize disadvantages and to internalize the logic of Western colonization.

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Publication Date
Tue Jan 01 2019
Journal Name
Journal Of Global Pharma Technology
Serum levels of cross-linked n-telopeptide of Type i collagen before and after non-surgical periodontal therapy in type 2 diabetic patients with chronic periodontitis
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Background: Diabetes mellitus is a major risk factor for chronic periodontitis (CP) and hyperglycemia has an important role in the enhancement of the severity of the periodontitis. It has been reported that the progression of CP causes shifting of the balance between bone formation and resorption toward osteoclastic resorption, and this will lead to the release of collagenous bone breakdown products into the local tissues and the systemic circulation. Cross-linked N-telopeptide of type I collagen (NTx) is the amino-terminal peptides of type I collagen which is released during the process of bone resorption. This study was conducted to determine the effects of nonsurgical periodontal therapy on serum level of NTx in type 2 diabetic patients

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Publication Date
Sun Dec 30 2012
Journal Name
Al-kindy College Medical Journal
Evaluation of Fludarabine, and granulocyte colony stimulating factor in treatment of efractory/Relapsed Acute Leukemias in adult Iraqi patients
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Background: Refractory/relapsed acute leukemia has always been a challenging problem for hematologist. Over the past decade emphasis has been made in the development of regimens containing fludarabine, combined with cytosine arabinoside for the treatment of refractory/relapsed acute leukemias. The aim of this study is to evaluate the efficacy and toxicity of the combination of fludarabine, high dose cytarabine, and granulocyte colony stimulating factor in refractory relapsed cases of acute leukaemia,
Methods: a prospective study is being conducted at the national center of hematology and hematology unit /Baghdad teaching hospital from July 2008 to July 2010.Twenty Patients with refractory/relapsed acute leukemia were treated with flud

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Publication Date
Sat Jun 30 2012
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Effect of Annealing on the Crystallization of Poly Vinyl Chloride for Drug Delivery System
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Poly vinyl alcohol has been studied for its ability to form crystallites by using annealing method. Semicrystalline films of poly vinyl alcohol (PVA) were prepared by casting 11.5 wt. % and 13 wt. % PVA aqueous solution onto glass slides at annealing temperature range 90 -120°C and duration time 15- 60 minute. This allowed the macromolecules to form crystallites, small regions of folded and compacted chains separated by amorphous regions where single PVA chain may pass through several of these crystallites. Degree of crystallinity of PVA films (hydrogels) was determined by method of density; on the other hand the swelling behavior was conducted by the determination of water uptake, wet degree of crystallinity, gel fraction and solubilit

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Publication Date
Sun Jan 01 2023
Journal Name
8th Engineering And 2nd International Conference For College Of Engineering – University Of Baghdad: Coec8-2021 Proceedings
Serviceability performance of high-strength concrete flexural members with internally unbonded post-tensioning strands
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