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https://www.readbyqxmd.com/read/29765016/b-cell-activation-and-plasma-cell-differentiation-are-inhibited-by-de-novo-dna-methylation
#1
Benjamin G Barwick, Christopher D Scharer, Ryan J Martinez, Madeline J Price, Alexander N Wein, Robert R Haines, Alexander P R Bally, Jacob E Kohlmeier, Jeremy M Boss
B cells provide humoral immunity by differentiating into antibody-secreting plasma cells, a process that requires cellular division and is linked to DNA hypomethylation. Conversely, little is known about how de novo deposition of DNA methylation affects B cell fate and function. Here we show that genetic deletion of the de novo DNA methyltransferases Dnmt3a and Dnmt3b (Dnmt3-deficient) in mouse B cells results in normal B cell development and maturation, but increased cell activation and expansion of the germinal center B cell and plasma cell populations upon immunization...
May 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29725449/high-expression-of-ubiquitin-conjugating-enzyme-e2a-predicts-poor-prognosis-in-hepatocellular-carcinoma
#2
Jian-Dong Shen, Shou-Zhong Fu, Lin-Ling Ju, Yi-Fang Wang, Feng Dai, Zhao-Xiu Liu, Han-Zheng Ji, Jian-Guo Shao, Zhao-Lian Bian
The present study aimed to illustrate the association of the expression of ubiquitin-conjugating enzyme E2A (UBE2A) with the clinicopathological parameters and prognosis in hepatocellular carcinoma (HCC). The expression levels of UBE2A mRNA and protein in a total of 276 HCC tissues and six liver cell lines was detected by fluorescent quantitative polymerase chain reaction, western blotting and immunohistochemistry. Statistical analysis was also performed to assess the association of the expression of UBE2A with the clinicopathological parameters and prognosis by the GraphPad Prism and SPSS version 21...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29715488/advanced-multigene-expression-system-for-nannochloropsis-salina-using-2a-self-cleaving-peptides
#3
Hyun Gi Koh, Nam Kyu Kang, Eun Kyung Kim, Seungjib Jeon, Sung-Eun Shin, Bongsoo Lee, Yong Keun Chang
Even though there has been much interest in genetic engineering of microalgae, its progress has been slow due to the difficulty and limitation of available techniques. Currently, genetic modification in most microalgal strains is confined to single gene transformation. Here, a multigene expression system for the oleaginous model strain Nannochloropsis salina was developed with glycine-serine-glycine spacer linked 2A self-cleaving peptides (2A) for the first time. An efficiency test of the four most widely used 2As revealed that two different types of 2As T2A and E2A have the best performance in N...
April 28, 2018: Journal of Biotechnology
https://www.readbyqxmd.com/read/29713515/the-role-of-tal1-in-hematopoiesis-and-leukemogenesis
#4
E R Vagapova, P V Spirin, T D Lebedev, V S Prassolov
TAL1 (SCL/TAL1, T-cell acute leukemia protein 1) is a transcription factor that is involved in the process of hematopoiesis and leukemogenesis. It participates in blood cell formation, forms mesoderm in early embryogenesis, and regulates hematopoiesis in adult organisms. TAL1 is essential in maintaining the multipotency of hematopoietic stem cells (HSC) and keeping them in quiescence (stage G0). TAL1 forms complexes with various transcription factors, regulating hematopoiesis (E2A/HEB, GATA1-3, LMO1-2, Ldb1, ETO2 , RUNX1, ERG, FLI1)...
January 2018: Acta Naturae
https://www.readbyqxmd.com/read/29705861/the-prognostic-role-of-e2a-pbx1-expression-detected-by-real-time-quantitative-reverse-transcriptase-polymerase-chain-reaction-rq-pcr-in-b-cell-acute-lymphoblastic-leukemia-after-allogeneic-hematopoietic-stem-cell-transplantation
#5
Yan Hong, Xiaosu Zhao, Yazhen Qin, Songhai Zhou, Yingjun Chang, Yu Wang, Xiaohui Zhang, Lanping Xu, Xiaojun Huang
The E2A-PBX1 rearrangement is common in B cell acute lymphoblastic leukemia (B-ALL). However, whether this fusion gene can be used as a reliable marker for minimal residual disease (MRD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unknown. In this study, clinical data were collected from 28 consecutive B-ALL patients who received allo-HSCT. Their MRD was evaluated by E2A-PBX1 and leukemia-associated immunophenotype (LAIP). The median follow-up was 374 days (55-2342 days)...
April 28, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29694893/setdb2-links-e2a-pbx1-to-cell-cycle-dysregulation-in-acute-leukemia-through-cdkn2c-repression
#6
Chiou-Hong Lin, Stephen Hon-Kit Wong, Jason H Kurzer, Corina Schneidawind, Michael C Wei, Jesús Duque-Afonso, Johan Jeong, Xuhui Feng, Michael L Cleary
Acute lymphoblastic leukemia (ALL) is associated with significant morbidity and mortality, necessitating further improvements in diagnosis and therapy. Targeted therapies directed against chromatin regulators are emerging as promising approaches in preclinical studies and early clinical trials. Here, we demonstrate an oncogenic role for the protein lysine methyltransferase SETDB2 in leukemia pathogenesis. It is overexpressed in pre-BCR+ ALL and required for their maintenance in vitro and in vivo. SETDB2 expression is maintained as a direct target gene of the chimeric transcription factor E2A-PBX1 in a subset of ALL and suppresses expression of the cell-cycle inhibitor CDKN2C through histone H3K9 tri-methylation, thus establishing an oncogenic pathway subordinate to E2A-PBX1 that silences a major tumor suppressor in ALL...
April 24, 2018: Cell Reports
https://www.readbyqxmd.com/read/29551033/-anti-cd19-chimeric-antigen-receptors-t-cells-for-treatment-of-relapsed-or-refractory-e2a-pbx1-positive-acute-lymphoblastic-leukemia-three-cases-report-and-literatures-review
#7
F Yang, J Zhang, H Y Qiu, Q Wu, D Q Kong, J J Han, J Q Qi, Y Han, D P Wu
No abstract text is available yet for this article.
January 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/29416542/id-proteins-suppress-e2a-driven-invariant-natural-killer-t-cell-development-prior-to-tcr-selection
#8
Sumedha Roy, Amanda J Moore, Cassandra Love, Anupama Reddy, Deepthi Rajagopalan, Sandeep S Dave, Leping Li, Cornelis Murre, Yuan Zhuang
A family of transcription factors known as E proteins, and their antagonists, Id proteins, regulate T cell differentiation at critical developmental checkpoints. Id proteins promote the differentiation of conventional αβ T cells and suppress the expansion of innate-like αβ T cells known as invariant natural killer T (iNKT) cells. However, it remains to be determined whether Id proteins differentially regulate these distinct lineage choices in early stages of T cell development. In this manuscript, we report that in Id-deficient mice, uninhibited activity of the E protein family member E2A mediates activation of genes that support iNKT cell development and function...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29407587/high-frequency-of-intermediate-and-poor-risk-copy-number-abnormalities-in-pediatric-cohort-of-b-all-correlate-with-high-mrd-post-induction
#9
Minu Singh, Prateek Bhatia, Amita Trehan, Neelam Varma, Manupdesh Singh Sachdeva, Deepak Bansal, Richa Jain, Shano Naseem
Copy number abnormalities (CNAs) and recurrent fusion transcripts are important genetic events which define and prognosticate B-Cell Acute Lymphoblastic Leukemia (B-ALL). We evaluated CNAs and fusion transcripts in 67 pediatric B-ALL cases and correlated the data with standard risk factors and early treatment outcome parameters. Common fusion transcripts ETV6-RUNX1, E2A-PBX, BCR-ABL1 and MLL-AF4 were examined by RT-PCR and noted in 15%, 15%, 13% and 1.4% of all cases respectively. CNAs in IKZF1, PAX5, EBF1, BTG1, RB1, CDKN2A/B and genes from PAR1 region viz...
March 2018: Leukemia Research
https://www.readbyqxmd.com/read/29348878/identification-of-cancer-prognosis-associated-functional-modules-using-differential-co-expression-networks
#10
Wenshuai Yu, Shengjie Zhao, Yongcui Wang, Brian Nlong Zhao, Weiling Zhao, Xiaobo Zhou
The rapid accumulation of cancer-related data owing to high-throughput technologies has provided unprecedented choices to understand the progression of cancer and discover functional networks in multiple cancers. Establishment of co-expression networks will help us to discover the systemic properties of carcinogenesis features and regulatory mechanisms of multiple cancers. Here, we proposed a computational workflow to identify differentially co-expressed gene modules across 8 cancer types by using combined gene differential expression analysis methods and a higher-order generalized singular value decomposition...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29298692/an-in-vivo-comparison-of-stimulated-echo-and-motion-compensated-spin-echo-sequences-for-3-t-diffusion-tensor-cardiovascular-magnetic-resonance-at-multiple-cardiac-phases
#11
Andrew D Scott, Sonia Nielles-Vallespin, Pedro F Ferreira, Zohya Khalique, Peter D Gatehouse, Philip Kilner, Dudley J Pennell, David N Firmin
BACKGROUND: Stimulated-echo (STEAM) and, more recently, motion-compensated spin-echo (M2-SE) techniques have been used for in-vivo diffusion tensor cardiovascular magnetic resonance (DT-CMR) assessment of cardiac microstructure. The two techniques differ in the length scales of diffusion interrogated, their signal-to-noise ratio efficiency and sensitivity to both motion and strain. Previous comparisons of the techniques have used high performance gradients at 1.5 T in a single cardiac phase...
January 3, 2018: Journal of Cardiovascular Magnetic Resonance
https://www.readbyqxmd.com/read/29284783/cd150-and-cd180-are-involved-in-regulation-of-transcription-factors-expression-in-chronic-lymphocytic-leukemia-cells
#12
I Gordiienko, L Shlapatska, V M Kholodniuk, L Kovalevska, T S Ivanivskaya, S P Sidorenko
BACKGROUND: Sequential stages of B-cell development is stringently coordinated by transcription factors (TFs) network that include B-lineage commitment TFs (Ikaros, Runx1/Cbfb, E2A, and FOXO1), B-lineage maintenance TFs (EBF1 and PAX5) and stage specific set of TFs (IRF4, IRF8, BCL6, BLIMP1). Deregulation of TFs expression and activity is often occurs in malignant B cells. The aim of this study was to evaluate TFs expression in chronic lymphocytic leukemia cells taking into consideration CD150 cell surface expression...
December 2017: Experimental Oncology
https://www.readbyqxmd.com/read/29182685/mir205-inhibits-stem-cell-renewal-in-sum159pt-breast-cancer-cells
#13
Víctor Mayoral-Varo, Annarica Calcabrini, María Pilar Sánchez-Bailón, Jorge Martín-Pérez
miR205 has a dual activity, as tumor suppressor and as oncogene. Here we analyzed the impact of miR205 ectopic expression in the initial tumorigenic processes of SUM159PT, a triple negative breast cancer cell line with low endogenous levels of miR205. In SUM159PT, miR205 inhibited expression of its targets VEGFA, ErbB3, Zeb1, Fyn and Lyn A/B; it reduced cell proliferation, and Myc/cyclin D1 levels, while increased p27kip1 expression. miR205 abolished anchorage-independent growth, inhibited migration and invasion, Src-kinases/Stat3 axis activation, and levels of secreted MMP9...
2017: PloS One
https://www.readbyqxmd.com/read/29132012/distinct-ezrin-truncations-differentiate-metastases-in-sentinel-lymph-nodes-from-unaffected-lymph-node-tissues-from-primary-breast-tumors-and-from-healthy-glandular-breast-tissues
#14
Claudia Röwer, Christian George, Toralf Reimer, Bernd Stengel, Anngret Radtke, Bernd Gerber, Michael O Glocker
BACKGROUND: Lymph node metastasis status is a prognostic factor for further lymph node involvement and for patient survival in breast cancer patients. Frozen section analysis of lymph nodes is a reliable method for detection of macro-metastases. However, this method is far less effective in detecting micro-metastases, requesting improved diagnostic procedures. METHODS: We investigated expression and truncation of ezrin in (i) sentinel lymph node metastases, (ii) unaffected axillary lymph nodes, (iii) primary breast tumors, and (iv) healthy glandular breast tissues using 2D gel electrophoresis, SDS-PAGE, and mass spectrometry in addition to Western blotting...
February 2018: Translational Oncology
https://www.readbyqxmd.com/read/29114388/epistatic-interactions-between-mutations-of-taci-tnfrsf13b-and-tcf3-result-in-a-severe-primary-immunodeficiency-disorder-and-systemic-lupus-erythematosus
#15
Rohan Ameratunga, Wikke Koopmans, See-Tarn Woon, Euphemia Leung, Klaus Lehnert, Charlotte A Slade, Jessica C Tempany, Anselm Enders, Richard Steele, Peter Browett, Philip D Hodgkin, Vanessa L Bryant
Common variable immunodeficiency disorders (CVID) are a group of primary immunodeficiencies where monogenetic causes account for only a fraction of cases. On this evidence, CVID is potentially polygenic and epistatic although there are, as yet, no examples to support this hypothesis. We have identified a non-consanguineous family, who carry the C104R (c.310T>C) mutation of the Transmembrane Activator Calcium-modulator and cyclophilin ligand Interactor (TACI, TNFRSF13B ) gene. Variants in TNFRSF13B /TACI are identified in up to 10% of CVID patients, and are associated with, but not solely causative of CVID...
October 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28990057/id3-may-protect-mice-from-anti%C3%A2-gbm-glomerulonephritis-by-regulating-the-differentiation-of-th17-and-treg-cells
#16
Huan Zhou, Le Wang, Qing Xu, Qingquan Liu, Hui Liu, Wenhui Qiu, Tingyang Hu, Yongman Lv, Qian Zhang
Anti‑glomerular basement membrane glomerulonephritis (anti‑GBM GN) is an autoimmune disease that leads to severe and rapidly progressive renal injury. Inhibition of DNA‑binding factor 3 (ID3) serves a key role in autoimmune diseases, such as asthma and Sjögren's syndrome, and in experimental allergic encephalitis models. However, the role of ID3 in the progression of anti‑GBM GN remains unknown. In the present study, ID3 mRNA expression increased between 3‑ and 20‑fold in the renal tissues of anti‑GBM GN mice compared with the Control group, with a peak at day 14 post‑induction...
December 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28939666/the-e2a-splice-variant-e47-regulates-the-differentiation-of-projection-neurons-via-p57-kip2-during-cortical-development
#17
Sabrina Pfurr, Yu-Hsuan Chu, Christian Bohrer, Franziska Greulich, Robert Beattie, Könül Mammadzada, Miriam Hils, Sebastian J Arnold, Verdon Taylor, Kristina Schachtrup, N Henriette Uhlenhaut, Christian Schachtrup
During corticogenesis, distinct classes of neurons are born from progenitor cells located in the ventricular and subventricular zones, from where they migrate towards the pial surface to assemble into highly organized layer-specific circuits. However, the precise and coordinated transcriptional network activity defining neuronal identity is still not understood. Here, we show that genetic depletion of the basic helix-loop-helix (bHLH) transcription factor E2A splice variant E47 increased the number of Tbr1-positive deep layer and Satb2-positive upper layer neurons at E14...
November 1, 2017: Development
https://www.readbyqxmd.com/read/28932193/safety-profile-of-anticancer-and-immune-modulating-biotech-drugs-used-in-a-real-world-setting-in-campania-region-italy-bio-cam-observational-study
#18
Cristina Scavone, Liberata Sportiello, Maria G Sullo, Carmen Ferrajolo, Rosanna Ruggiero, Maurizio Sessa, Pasquale M Berrino, Gabriella di Mauro, Liberato Berrino, Francesco Rossi, Concetta Rafaniello, Annalisa Capuano
Objectives: To investigate the occurrence of adverse events (AEs) in naïve patients receiving biotech drugs. Design: A prospective observational study. Setting: Onco-hematology, Hepato-gastroenterology, Rheumatology, Dermatology, and Neurology Units in Campania Region (Italy). Participants: 775 patients (53.81% female) with mean age 56.0 (SD 15.2). The mean follow-up/patient was 3.48 (95% confidence interval 3.13-3.84). Main outcome measures: We collected all AEs associated to biotech drugs, including serious infections and malignancies...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28851812/a-first-in-class-twist1-inhibitor-with-activity-in-oncogene-driven-lung-cancer
#19
Zachary A Yochum, Jessica Cades, Lucia Mazzacurati, Neil M Neumann, Susheel K Khetarpal, Suman Chatterjee, Hailun Wang, Myriam A Attar, Eric H-B Huang, Sarah N Chatley, Katriana Nugent, Ashwin Somasundaram, Johnathan A Engh, Andrew J Ewald, Yoon-Jae Cho, Charles M Rudin, Phuoc T Tran, Timothy F Burns
TWIST1, an epithelial-mesenchymal transition (EMT) transcription factor, is critical for oncogene-driven non-small cell lung cancer (NSCLC) tumorigenesis. Given the potential of TWIST1 as a therapeutic target, a chemical-bioinformatic approach using connectivity mapping (CMAP) analysis was used to identify TWIST1 inhibitors. Characterization of the top ranked candidates from the unbiased screen revealed that harmine, a harmala alkaloid, inhibited multiple TWIST1 functions, including single-cell dissemination, suppression of normal branching in 3D epithelial culture, and proliferation of oncogene driver-defined NSCLC cells...
December 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28833410/direct-comparison-of-in-vivo-versus-postmortem-second-order-motion-compensated-cardiac-diffusion-tensor-imaging
#20
Christian T Stoeck, Constantin von Deuster, Thea Fleischmann, Miriam Lipiski, Nikola Cesarovic, Sebastian Kozerke
PURPOSE: To directly compare in vivo versus postmortem second-order motion-compensated spin-echo diffusion tensor imaging of the porcine heart. METHODS: Second-order motion-compensated spin-echo cardiac diffusion tensor imaging was performed during systolic contraction in vivo and repeated upon cardiac arrest by bariumchloride without repositioning of the study animal or replaning of imaging slices. In vivo and postmortem reproducibility was assessed by repeat measurements...
April 2018: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
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