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Epigenome-wide analysis reveals functional modulators of drug sensitivity and post-treatment survival in chronic lymphocytic leukaemia
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
Wed Apr 01 2009
Journal Name
Journal Of The Faculty Of Medicine Baghdad
Fibromyalgia Syndrome in Chronic Obstructive Pulmonary Disease

Background: Fibromyalgia syndrome is a common rheumatological syndrome with multiple systemic manifestations & associated with many diseases. The aim of the study is to assess the
possible association between fibromyalgia syndrome (FMS) & chronic obstructive pulmonary disease (COPD), and to correlate this association with patient's age, age group, sex, marital status, duration of the disease, & its severity.
Patients and Methods: Fifty patients with COPD & 50 healthy controls were included in this study. Full history was taken & complete physical examination was done for all patients in both groups. Disease characteristics [age, age group, sex, marital status, duration of the disease, &a

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Publication Date
Mon Jul 01 2013
Journal Name
Journal Of The Faculty Of Medicine Baghdad
Mutant P53 expression in chronic myeloid leukemia

Background: Chronic Myeloid Leukemia (CML) occurs due to malignant transformation of a pluripotent stem cell.  Progression is insidious from chronic to aggressive accelerated or blastic phases. Studies revealed a significant role of the tumor suppressor gene P53 in disease progression.

Objectives: To evaluate the immunohistochemical expression of mutant P53 protein in CML at different clinical phases.

J Fac Med Baghdad

2013; Vol.55, No .3

Received Nov .2012

Accepted July.2013

 

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Publication Date
Tue Sep 01 2020
Journal Name
Baghdad Science Journal
Improving the Durability of Streak and Thermal Insulation of Petroleum Pipes by Using Polymeric Based Paint System: Polymer Matrix Composites have several and wide applications

This research deals with increasing the hardening and insulating the petroleum pipes against the conditions and erosion of different environments. So, basic material of epoxy has been mixed with Ceramic Nano Zirconia reinforcement material 35 nm with the percentages  (0,1,2,3,4,5) %, whereas the paint basis of broken petroleum pipes was used  to paint on it, then it was cut into dimensions (2 cm. × 2 cm.) and 0.3cm high. After the paint and percentages are completed, the samples were immersed into the paint. Then, the micro-hardness was checked according to Vickers method and thermal inspection of paint, which contained (Thermal conduction, thermal flux and Thermal diffusivity), the density of the painted samples was calculate

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Publication Date
Sun Apr 01 2018
Journal Name
Journal Of The Faculty Of Medicine Baghdad
Growth of diabetic children in post conflict Baghdad, Iraq

Background: previously type 1 diabetes mellitus (T1DM) was listed among the causes of severing growth retardation. Iraq was exposed to wars and conflicts that affect health services which in turn affect the glycemic state of diabetic patients.
Objective: To report on the growth of diabetic children in post-conflict Iraq.
Methods: A total of 100 children with T1DM were included in the study. They were attending the consultancy clinic in Children Welfare Teaching Hospital for the period from 1st of Feb to 30th of May 2017. Weight and height were measured. The growth indices at diagnosis were taken from a case file.
Results: A total of 100 children with T1DM included in this study. Their age was 9.3 ± 3.2 years with a male to fema

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Publication Date
Wed Jan 01 2014
Journal Name
Veterinary Medicine International
Compensatory Structural Adaptive Modifications of Vagina in Response to Functional Demand in Goat

Vaginal biopsies and smears were collected from ten adult local healthy goats. Routine histological methods were carried out on vaginal biopsies and then stained with PAS stain. The smears were stained with Methylene blue. All samples were inspected under light microscope. The present study found that many constituents of the wall of the vagina, which have an important functional role, were absent; among these were the vaginal glands, goblet cells, muscularis mucosa, and lymphatic nodules. On the other hand, vagina showed special compensatory histological mechanisms, namely, the deep epithelial folds, the well-developed germinated stratum basale, the apparent basement membrane, and the profuse defensive cells, such as neutrophils, m

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Publication Date
Mon Jun 15 2020
Journal Name
Al-academy
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Publication Date
Mon Jan 01 2024
Journal Name
Journal Of The College Of Languages (jcl)
Negation marker in Standard Persian : a typological analysis based on Givon’s functional model: عامل نفی در زبان فارسی معیار: بررسی رده‌شناختی براساس مدل نقش‌ گرایی گیون

 Abstract:

Typological analysis about  the negation marker  in different languages is one of the fields of research that has attracted much attention.  In Persian language, this constituent has been analysed from different aspects. This study aimed to analyse  different aspects of negation marker  in  the adjectives,  the noun phrases and  the verb phrases based on typological analysis.  Many studies have been revealed that  the negation in adjectives has shown lexically and morphologically. In the noun phrases, /hich/  has used as a negative marker necessarily marking the verb phrase as negative too. In the verb phrases, negation occurs morphologically by the addition of the prefix /n

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Publication Date
Wed Dec 29 2021
Journal Name
Journal Of Legal Sciences
Standard functional solution within the framework of multinationality

One of the most significant difficulties raised by the phenomenon of multiple nationalities is the designation of the law applicable to the dispute involving a foreign element in which the rules of attribution refer to the application of personal law in matters of personal status, which has resulted in jurisprudence and jurisprudence in this area to several criteria that can be applied to weighting one of the nationalities held by the foreign national, as well as the position of national legislation that adopted the most likely of these standards, It can be embodied in two traditional directions represented by the standards of the judge 's law and the law of actual nationality, while the modern trend is the criterion of functional soluti

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Publication Date
Sun Sep 03 2017
Journal Name
Baghdad Science Journal
Preparation and Characterization some New of Naproxen Drug Derivatives

In this research four steps of the new derivatives of Naproxen drug have been made which are known as a high medicinal effectiveness; the first step involved converting Naproxen into the corresponding ester (A) by reaction Naproxen with methanol absolute in presence H2SO4. While the second step involved treatment methyl Naproxen ester (A) with hydrazine hydrate 80% in presence of ethanol .The third reaction requires synthesis of Schiff bases (C1-C10) by condensation. of Naproxen hydrazide (B) with many substituted aromatic aldehydes . Finally, the fourth step synthesized new tetrazole derivatives ( D1- D10) by the reaction of the prepared Schiff bases (in the third step) with Sodium azide in THF as a solvent .The prepared compounds wer

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Publication Date
Sun Sep 01 2013
Journal Name
Baghdad Science Journal
In Vitro Study of MefenamateStarch as Drug Delivery System

Mefenamic acid was esterified with starchwith[1:1] Molar ratio, as drug substituted with natural polymer, to prolongthe period of hydrolysis of drug polymer with other advantages. The new prodrug starch was characterized by FT-IR and UV-Visible and 1H-NMR spectroscopies. The physical properties were studied and controlled drug release was studied in different pH values at 37oC. The stability of drug was carried out by measuring the absorbance of mefenamic starch which hydrolyzed in HCl solution of pH 1.1 (artificial gastric fluid) and phosphate buffer of pH 7.4 (simulating intestinal fluid SIF) at 37oC for several days. The thermal analysis such as DSC was studied.

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