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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 Aug 28 2018
Journal Name
Journal Of Pharmaceutical Sciences And Research
Schiff base complexes of some drug substances (Review)
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Schiff bases (SBs) represent multipurpose ligands that can be prepared from the concentration of prime amines with carbonyl clusters. Creation of SB transition metal compounds via as ligands has opportunity of attaining coordination complexes of abnormal arrangement and stability. These transition metal compounds have extraordinary attention as a consequence of their dynamic portion in metalloenzymes and as biomimetic prototypical complexes as a result of their proximity to usual enzymes and proteins. These complexes are imperative in medicinal disciplines owing to their widespread range of biological actions. They mostly exhibit organic actions involving antifungal, antibacterial, antitumor, antidiabetic, herbicidal, antiproliferative, ant

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Publication Date
Sat Jun 01 2024
Journal Name
Annals Of Applied Sport Science
The Psychological Well-being and Its Relationship with the Functional Creativity of Female Gymnastics’ Trainers
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Publication Date
Fri Nov 22 2019
Journal Name
Chalcogenide Letters
CONCENTRATION EFFECTS ON ELECTRONIC AND SPECTROSCOPIC PROPERTIES OF ZnCdS WURTZOIDS: A DENSITY FUNCTIONAL THEORY STUDY
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Publication Date
Tue Aug 01 2023
Journal Name
Dna Repair
The interactions between DNA methylation machinery and long non-coding RNAs in tumor progression and drug resistance
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DNA methylation is one of the main epigenetic mechanisms in cancer development and progression. Aberrant DNA methylation of CpG islands within promoter regions contributes to the dysregulation of various tumor suppressors and oncogenes; this leads to the appearance of malignant features, including rapid proliferation, metastasis, stemness, and drug resistance. The discovery of two important protein families, DNA methyltransferases (DNMTs) and Ten-eleven translocation (TET) dioxygenases, respectively, which are responsible for deregulated transcription of genes that play pivotal roles in tumorigenesis, led to further understanding of DNA methylation-related pathways. But how these enzymes can target specific genes in different malignancies;

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Publication Date
Thu Jun 30 2022
Journal Name
Journal Of Economics And Administrative Sciences
Estimation of Time of Survival Rate by Using Clayton Function for the Exponential Distribution with Practical Application
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Each phenomenon contains several variables. Studying these variables, we find mathematical formula to get the joint distribution and the copula that are a useful and good tool to find the amount of correlation, where the survival function was used to measure the relationship of age with the level of cretonne in the remaining blood of the person. The Spss program was also used to extract the influencing variables from a group of variables using factor analysis and then using the Clayton copula function that is used to find the shared binary distributions using multivariate distributions, where the bivariate distribution was calculated, and then the survival function value was calculated for a sample size (50) drawn from Yarmouk Ho

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Publication Date
Thu Feb 07 2019
Journal Name
Journal Of The College Of Education For Women
Search for Identity in Michael Ondaatje's Post colonial Novel In the Skin of a Lion
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In his post colonial novel, In the Skin of a lion, the Canadian/Sri Lankan writer,
Michael Ondaatje is so interested in the term "Post colonialism" because he wants to show
that the term doesn't only refer to a period of time that comes after colonialism. In other
words, post colonialism is not only referred to as a literal description of formerly colonial
societies. He deals with the termas a literary genre and an academic construct that describes
the global conditions of a man after a period of colonialism. He shows that post colonialism is
a theory that tries to examine and explore the different styles and faces of European authority
to control the colonized. Ondaatje's attempt through such term is to unmask Europ

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Publication Date
Fri Jan 01 2021
Journal Name
International Journal Of Agricultural And Statistical Sciences
DYNAMIC MODELING FOR DISCRETE SURVIVAL DATA BY USING ARTIFICIAL NEURAL NETWORKS AND ITERATIVELY WEIGHTED KALMAN FILTER SMOOTHING WITH COMPARISON
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Survival analysis is widely applied in data describing for the life time of item until the occurrence of an event of interest such as death or another event of understudy . The purpose of this paper is to use the dynamic approach in the deep learning neural network method, where in this method a dynamic neural network that suits the nature of discrete survival data and time varying effect. This neural network is based on the Levenberg-Marquardt (L-M) algorithm in training, and the method is called Proposed Dynamic Artificial Neural Network (PDANN). Then a comparison was made with another method that depends entirely on the Bayes methodology is called Maximum A Posterior (MAP) method. This method was carried out using numerical algorithms re

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Publication Date
Fri Nov 01 2013
Journal Name
Iraqi Postgraduate Medical Journal
Post Hair Epilation Acneiform Eruption Among Females
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KE Sharquie, HR Al-Hamami, IK Sharquie, AA Noaimi, HM Al-Karawy, Iraqi Postgraduate Medical Journal, 2013

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Publication Date
Fri Jul 22 2022
Journal Name
Biochemical And Cellular Archive
HEPATITIS B VIRUS GENOTYPES IN IRAQI PATIENTS WITH CHRONIC HEPATITIS B INFECTION
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Hepatitis B virus (HBV) infection is a serious disease of the liver and signifies a major worldwide health concern. HBV Genotyping is vital for further epidemiological study, predicting the disease outcome and response to treatment. The current study aimed to determine hepatitis B virus genotypes in patients with chronic hepatitis B, and to validate possible associations with the baseline characteristics of the disease. A total of 90 patients with chronic hepatitis B infection were enrolled in this study. Liver function tests, hepatitis B virus markers and DNA viral load were done using routine standardized procedures. HBV genotyping was performed using real time PCR. Genotype D was the most predominant in 64 (71.1%) of samples, while

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Publication Date
Sat Jan 01 2022
Journal Name
Materials Today: Proceedings
Application of levofloxacin and doxycycline in treatment of vaginal chlamydial infection
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Doxycycline and levofloxacin are heterocyclic organic compounds that are now popularly used to treat some bacterial infections. In this study which was conducted on patients from a private clinic, we compared the use of two commonly used antibiotics for the treatment of diagnosed cases with vaginal chlamydial infection: levofloxacin and doxycycline. Vaginal chlamydial infection is considered to be a very common sexually transmitted infection. It may have minimal symptoms which can lead to neglect by the patient until it leads to some important complications among which is the inability to become pregnant. This indicates early diagnosis and treatment of this infection. By comparing the results of treatment we concluded that there is no much

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