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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 Jan 17 2025
Journal Name
Opera Medica Et Physiologica
ASSESSMENT OF THE HARMFUL EFFECT OF DUPROST DRUG ON TESTES OF ALBINO MICE
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Publication Date
Tue Dec 23 2025
Journal Name
Journal Of Baghdad College Of Dentistry
The Clinical Approach and Treatment of Benign and Malignant Parotid Masses
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Background: Parotid gland tumors account for 80% of all salivary gland neoplasms, 20% of these are malignant, but in daily clinical practice most parotid masses are operated on before obtaining the final histological diagnosis. This clinical setting further complicates the critical point of parotid surgery, which is the management of the facial nerve. Materials and methods: 45 patients underwent parotidectomy for benign and malignant neoplasms. A complete history is collected from the patients with the duration and the site of the tumor, the facial nerve examined and its associations, a medical consultation done for opinion and management. Clinical examination with facial nerve was mandatory to avoid any mistakes that may occur. The most si

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Publication Date
Wed Dec 30 2020
Journal Name
Al-kindy College Medical Journal
Various types of Alopecia and the options of the treatment
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Alopecia (Baldness) is very usual trouble in current time. It is accompanied by an intensive weakening of the scalp's hair and follows a specific pattern. Hereditary predisposition plays a very important role in alopecia despite not completely understood. Alopecia can be typed to various categories according to etiology, may be due to hereditary factors, autoimmune disease, and drugs or chemicals. There are many options of strategies of treatment according to the type and causes of alopecia. Chemical or synthetic medications apply for the management of hair loss are accompanied by a wide range of undesirable effects. Naturally occurring drugs also play important role in alopecia management with minimal side effects.

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Publication Date
Thu Jan 08 2015
Journal Name
Chemical And Process Engineering Research
Uni and Simplex Optimization for the Spectrophotometric Determination of Erythromycin ethylsuccinate Drug via Charge-Transfer Complex Formation
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Charge transfer complex formation method has been applied for the spectrophotometric determination of erythromycin ethylsuccinate, in bulk sample and dosage form. The method was accurate, simple, rapid, inexpensive and sensitive depending on the formed charge- transfer complex between cited drug and, 2,3- Dichloro-5,6-dicyano-p- benzoquinone (DDQ) as a chromogenic reagent. The formed complex shows absorbance maxima at 587 nm against reagent blank. The calibration graph is linear in the ranges of (10 - 110) μg.mL-1 with detection limit of 0.351μg.mL-1. The results show the absence of interferences from the excipients on the determination of the drug. Therefore the proposed method has been successfully applied for the determination of eryth

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Publication Date
Sun May 10 2020
Journal Name
Baghdad Science Journal
Characterization and Biological Activity of Some New Derivatives Derived from Sulfamethoxazole Compound: new derivatives from sulfamethoxazole drug.
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 A new series of Sulfamethoxazole derivatives was prepared and examined for antifibrinolytic and antimicrobial activities. Sulfamethoxazole derivatives bear heterocyclic moieties such as 1,3,4-thiadiazine {3},  pyrazolidine-3,5-diol {4} 6-hydroxy-1,3,4-thiadiazinane-2-thione {5} and [(3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-4-yl)diazenyl] {8}. Their structures were elucidated by spectral methods (FT-IR, H1-NMR). Physical properties are also determined for all compound derivatives.  Recently prepared compounds were tested for their antimicrobial activity in the laboratory. Each screened compound showed good tendency to moderate antimicrobial activity.

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Publication Date
Sat Oct 01 2022
Journal Name
Baghdad Science Journal
Designing and Synthesising Novel Benzophenone Biscyclic Imides Comprising Drug Moity with Investigating their Antimicrobial Activity
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The present work involved designing and synthesizing of a series of new. compounds which their molecules are composed from two biologically active components namely sulfamethoxazole or β-lactam containing drugs and cyclic imides. The target new compounds were synthesized by two steps in the first one a series of six bis (N-drug phthalamic acid_4-yl) ketone (1-6) were prepared from the reaction of sulfamethoxazole or β-lactam containing drugs with benzophenone 3, 3′, 4, 4′ -tetracarboxylic dianhydride.

In the second step, compounds (1-6) were introduced in dehydration reaction via fusion process producing the target compounds bis (N-drug phthalimidyl-4-yl) ketone (7-12). The antibacterial and antifungal high

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Publication Date
Sun Dec 06 2015
Journal Name
Baghdad Science Journal
The Spectrophotometric Determination of Famotidine Drug via Coupling with Diazotized Metochlopramide Hydrochloride
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A new, simple and sensitive spectrophotometric method was described for the determination of famotidine (FAM) as a pure material and in pharmaceutical formulation. This method was based on diazotization and coupling reaction between famotidine and diazotized solution of metochlopramide hydrochloride (DMPH) in the presence of phosphate buffer solution to give a compound of azo dye having orange color soluble in water with high absorptivity at a wave length of 478 nm. The data shows that FAM and DMPH combine in the molar ratio of 1:1 at PH 7.0 .The method obeys Beer's law over concentration range of 1-40 ?g.ml-1 of famotidine with a correlation coefficient of 0.9955 and a detection limit of 0.10 ?g.ml-1. The apparent molar absorptivity re

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Publication Date
Tue Jul 02 2013
Journal Name
Journal Of Baghdad College Of Dentistry
Local Drug Delivery Systems for Treating Periodontal Diseases: A Review of Literature
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Publication Date
Tue Dec 23 2025
Journal Name
Journal Of Baghdad College Of Dentistry
Local drug delivery systems for treating periodontal diseases (A review of literature)
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In this review of literature, the light will be concentrated on the local drugs delivery systems for treating the periodontal diseases. Principles, types, advantages and indications of each type will be discussed in this paper.

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Publication Date
Fri Jul 05 2024
Journal Name
Journal Of Applied Spectroscopy
Spectrophotometric Method Using the Derivative for the Determination of the Drug Losartan
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