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https://www.readbyqxmd.com/read/28758047/the-role-of-the-ikaros-family-of-transcription-factors-in-regulatory-t-cell-development-and-function
#1
Amara Seng, Thomas M Yankee
Regulatory T (Treg) cells are a subset of immune cells that maintain homeostasis by promoting immune tolerance and suppressing the immune response via a variety of mechanisms such as secreting cytokines, killing reactive immune cells, and inducing anergy. Dysfunction of Treg cells has been implicated in inflammatory diseases such as autoimmunity and transplant rejection. Conversely, too many or hyperresponsive Treg cells has been observed in cancer and chronic infections. Treg cells have proven to be difficult to study as there are no definitive Treg surface markers...
April 2017: Journal of Clinical & Cellular Immunology
https://www.readbyqxmd.com/read/28751559/loss-of-function-but-not-dominant-negative-intragenic-ikzf1-deletions-are-associated-with-an-adverse-prognosis-in-adult-bcr-abl-negative-acute-lymphoblastic-leukemia
#2
Benjamin Kobitzsch, Nicola Gökbuget, Stefan Schwartz, Richard Reinhardt, Monika Brüggemann, Andreas Viardot, Ralph Wäsch, Michael Starck, Eckhard Thiel, Dieter Hoelzer, Thomas Burmeister
Genetic alterations of the transcription factor IKZF1 ("IKAROS") are detected in around 15-30% of cases of BCR-ABL-negative B-cell precursor acute lymphoblastic leukemia (ALL). Different types of intragenic deletions have been observed, resulting in a functionally inactivated allele ("loss-of-function") or in "dominant-negative" isoforms. The prognostic impact of these alterations especially in adult acute lymphoblastic leukemia is not well defined. We analyzed 482 well-characterized cases of adult BCR-ABL-negative B-precursor acute lymphoblastic leukemia uniformly treated in the framework of the GMALL studies and detected IKZF1 alterations in 128 cases (27%)...
July 27, 2017: Haematologica
https://www.readbyqxmd.com/read/28751557/the-bet-bromodomain-inhibitor-cpi203-improves-lenalidomide-and-dexamethasone-activity-in-in-vitro-and-in-vivo-models-of-multiple-myeloma-by-blockade-of-ikaros-and-myc-signaling
#3
Tania Díaz, Vanina Rodríguez, Ester Lozano, Mari-Pau Mena, Marcos Calderón, Laura Rosiñol, Antonio Martínez, Natalia Tovar, Patricia Pérez-Galán, Joan Bladé, Gaël Roué, Carlos Fernández de Larrea
Most of patients with multiple myeloma treated with current therapies, including immunomodulatory drugs, eventually develop relapsed/refractory disease. Clinical activity of lenalidomide relies on degradation of Ikaros and the consequently reduction on IRF4 expression, both required for myeloma cell survival and involved in the regulation of MYC transcription. Thus, we sought to determine the combinatorial effect of a MYC-interfering therapy with lenalidomide/dexamethasone. We analyzed the potential therapeutic effect of the combination of BET bromodomain inhibitor CPI203 with the lenalidomide/dexamethasone regimen in myeloma cell lines...
July 27, 2017: Haematologica
https://www.readbyqxmd.com/read/28707666/-identification-of-proteins-associated-with-transcription-factors-hoxa9-and-e2a-pbx1-by-tandem-affinity-purification
#4
E A Shestakova, M Boutin, S Bourassa, E Bonneil, J J Bijl
Chimeric transcription factor E2A-PBX1 induces the development of acute lymphoblastic B-cell leukemia in children. Using a transgenic mouse model, we previously demonstrated that homeobox (HOX) gene HOXA9 genetically interact with E2A-PBX1 gene in the development of B-cell leukemia in mice. HOXA9 itself is a potent oncogene resulting in myeloid leukemia when overexpressed, which is strongly accelerated by its collaborator Meis1. HOX, PBX1 and MEIS1 proteins have been shown to form hetero dimeric or trimeric complexes in different combinations...
May 2017: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/28696334/recent-advances-in-heart-sound-analysis
#5
Gari D Clifford, Chengyu Liu, Benjamin E Moody, José Millet Roig, Samuel E Schmidt, Qiao Li, Ikaro Silva, Roger G Mark
Heart sounds have been widely studied and have been demonstrated to have value for detecting pathologies in clinical applications. Over the last few decades, the use of heart sound signals has become increasingly uncommon and its practice in modern medicine somewhat diminished, although research into automated analysis has continued. Unfortunately, a comparative analyses of algorithms in the literature have been hindered by the lack of high-quality, rigorously validated, and standardized open databases of heart sound recordings...
July 11, 2017: Physiological Measurement
https://www.readbyqxmd.com/read/28670688/lack-of-ikaros-cripples-expression-of-foxo1-and-its-targets-in-naive-t-cells
#6
Parul Agnihotri, Nicholas M Robertson, Sarah E Umetsu, Ksenia Arakcheeva, Susan Winandy
Ikaros is a transcription factor that regulates lymphocyte development from the level of the hematopoietic stem cell. Lack of Ikaros reduces the ability of progenitor cells to commit to the T cell lineage, resulting in reduced numbers of early thymic T cell progenitors and mature T cells. Mature CD4 T cells that lack Ikaros have defects in proliferation, T helper cell differentiation, cytokine expression and the ability to become anergic. A role for Ikaros in the naïve T cell has not yet been identified. IL-7Rα and L-selectin are receptors important for ensuring survival and proper homing of naive T cells, respectively...
July 3, 2017: Immunology
https://www.readbyqxmd.com/read/28670491/the-transcription-factor-ikaros-inhibits-cell-proliferation-by-downregulating-anxa4-expression-in-hepatocellular-carcinoma
#7
Yi-Yao Liu, Chao Ge, Hua Tian, Jing-Yi Jiang, Fang-Yu Zhao, Hong Li, Tao-Yang Chen, Ming Yao, Jin-Jun Li
The occurrence and progression of hepatocellular carcinoma (HCC) are affected by complicated signal transduction factors. Our previous study identified Ikaros as a novel reactivated therapeutic target that acts as a transcriptional repressor and reactivates anticancer mechanisms in HCC therapy. Annexin A4 (ANXA4) is a member of the Annexin family that plays an essential role in several cancers, but it has not been investigated in HCC proliferation. Using cDNA microarrays, ANXA4 was shown to be associated with Ikaros in Ikaros-overexpressing cells...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28654293/optical-emission-in-hexagonal-sige-nanowires
#8
Xavier Cartoixà, Maurizia Palummo, Håkon Ikaros T Hauge, Erik P A M Bakkers, Riccardo Rurali
Recent advances in the synthetic growth of nanowires have given access to crystal phases that in bulk are only observed under extreme pressure conditions. Here, we use first-principles methods based on density functional theory and many-body perturbation theory to show that a suitable mixing of hexagonal Si and hexagonal Ge yields a direct bandgap with an optically permitted transition. Comparison of the calculated radiative lifetimes with typical values of nonradiative recombination mechanisms indicates that optical emission will be the dominant recombination mechanism...
July 3, 2017: Nano Letters
https://www.readbyqxmd.com/read/28643330/muc1-c-is-a-target-in-lenalidomide-resistant-multiple-myeloma
#9
Li Yin, Ashujit Tagde, Reddy Gali, Yu-Tzu Tai, Teru Hideshima, Kenneth Anderson, David Avigan, Donald Kufe
Lenalidomide (LEN) acts directly on multiple myeloma (MM) cells by inducing cereblon-mediated degradation of interferon regulatory factor 4, Ikaros (IKZF)1 and IKZF3, transcription factors that are essential for MM cell survival. The mucin 1 (MUC1) C-terminal transmembrane subunit (MUC1-C) oncoprotein is aberrantly expressed by MM cells and protects against reactive oxygen species (ROS)-mediated MM cell death. The present studies demonstrate that targeting MUC1-C with GO-203, a cell-penetrating peptide inhibitor of MUC1-C homodimerization, is more than additive with LEN in downregulating the WNT/β-catenin pathway, suppressing MYC, and inducing late apoptosis/necrosis...
June 23, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28623166/casein-kinase-ii-ck2-glycogen-synthase-kinase-3-gsk-3-and-ikaros-mediated-regulation-of-leukemia
#10
REVIEW
Chandrika Gowda, Mario Soliman, Malika Kapadia, Yali Ding, Kimberly Payne, Sinisa Dovat
Signaling networks that regulate cellular proliferation often involve complex interactions between several signaling pathways. In this manuscript we review the crosstalk between the Casein Kinase II (CK2) and Glycogen Synthase Kinase-3 (GSK-3) pathways that plays a critical role in the regulation of cellular proliferation in leukemia. Both CK2 and GSK-3 are potential targets for anti-leukemia treatment. Previously published data suggest that CK2 and GSK-3 act synergistically to promote the phosphatidylinositol-3 kinase (PI3K) pathway via phosphorylation of PTEN...
June 13, 2017: Advances in Biological Regulation
https://www.readbyqxmd.com/read/28596474/lenalidomide-increases-human-dendritic-cell-maturation-in-multiple-myeloma-patients-targeting-monocyte-differentiation-and-modulating-mesenchymal-stromal-cell-inhibitory-properties
#11
Federica Costa, Rosanna Vescovini, Marina Bolzoni, Valentina Marchica, Paola Storti, Denise Toscani, Fabrizio Accardi, Laura Notarfranchi, Benedetta Dalla Palma, Cristina Manferdini, Sabrina Manni, Giannalisa Todaro, Gina Lisignoli, Francesco Piazza, Franco Aversa, Nicola Giuliani
The use of Lenalidomide (LEN), to reverse tumor-mediated immune suppression and amplify multiple myeloma-specific immunity is currently being explored. Particularly, LEN effects on dendritic cells (DCs) are still unclear. In this study, we investigated the potential effect of LEN on DC differentiation and activity. DCs were differentiated either from CD14+ cells obtained from patients with multiple myeloma or from a human monocytic cell line.LEN, at the concentration range reached in vivo, significantly increased the median intensity expression of HLA-DR, CD86 and CD209 by DCs derived from both bone marrow and peripheral myeloma monocytes and enhanced the production of Interleukin-8, C-C motif chemokine ligand (CCL) 2, CCL5 and tumor necrosis factor-α...
May 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28591298/construction-and-validation-of-the-self-care-assessment-instrument-for-patients-with-type-2-diabetes-mellitus
#12
Simonize Cunha Barreto de Mendonça, Maria Lúcia Zanetti, Namie Okino Sawada, Ikaro Daniel de Carvalho Barreto, Joseilze Santos de Andrade, Liudmila Miyar Otero
Objective: to construct and validate the contents of the Self-care Assessment instrument for patients with type 2 diabetes mellitus. Method: methodological study, based on Orem's General Theory of Nursing. The empirical categories and the items of the instrument were elucidated through a focus group. The content validation process was performed by seven specialists and the semantic analysis by 14 patients. The Content Validity Indices of the items, ≥0.78, and of the scale, ≥0...
June 5, 2017: Revista Latino-americana de Enfermagem
https://www.readbyqxmd.com/read/28584103/neurog2-and-ascl1-together-regulate-a-postmitotic-derepression-circuit-to-govern-laminar-fate-specification-in-the-murine-neocortex
#13
Daniel J Dennis, Grey Wilkinson, Saiqun Li, Rajiv Dixit, Lata Adnani, Anjali Balakrishnan, Sisu Han, Christopher Kovach, Nicole Gruenig, Deborah M Kurrasch, Richard H Dyck, Carol Schuurmans
A derepression mode of cell-fate specification involving the transcriptional repressors Tbr1, Fezf2, Satb2, and Ctip2 operates in neocortical projection neurons to specify six layer identities in sequence. Less well understood is how laminar fate transitions are regulated in cortical progenitors. The proneural genes Neurog2 and Ascl1 cooperate in progenitors to control the temporal switch from neurogenesis to gliogenesis. Here we asked whether these proneural genes also regulate laminar fate transitions. Several defects were observed in the derepression circuit in Neurog2(-/-);Ascl1(-/-) mutants: an inability to repress expression of Tbr1 (a deep layer VI marker) during upper-layer neurogenesis, a loss of Fezf2(+)/Ctip2(+) layer V neurons, and precocious differentiation of normally late-born, Satb2(+) layer II-IV neurons...
June 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28570570/a-machine-learning-approach-for-gait-speed-estimation-using-skin-mounted-wearable-sensors-from-healthy-controls-to-individuals-with-multiple-sclerosis
#14
Ryan S McGinnis, Nikhil Mahadevan, Yaejin Moon, Kirsten Seagers, Nirav Sheth, John A Wright, Steven DiCristofaro, Ikaro Silva, Elise Jortberg, Melissa Ceruolo, Jesus A Pindado, Jacob Sosnoff, Roozbeh Ghaffari, Shyamal Patel
Gait speed is a powerful clinical marker for mobility impairment in patients suffering from neurological disorders. However, assessment of gait speed in coordination with delivery of comprehensive care is usually constrained to clinical environments and is often limited due to mounting demands on the availability of trained clinical staff. These limitations in assessment design could give rise to poor ecological validity and limited ability to tailor interventions to individual patients. Recent advances in wearable sensor technologies have fostered the development of new methods for monitoring parameters that characterize mobility impairment, such as gait speed, outside the clinic, and therefore address many of the limitations associated with clinical assessments...
2017: PloS One
https://www.readbyqxmd.com/read/28566276/fra-2-regulates-b-cell-development-by-enhancing-irf4-and-foxo1-transcription
#15
Kenia Ubieta, Mireia Garcia, Bettina Grötsch, Steffen Uebe, Georg F Weber, Merle Stein, Arif Ekici, Georg Schett, Dirk Mielenz, Aline Bozec
The role of AP-1 transcription factors in early B cell development and function is still incompletely characterized. Here we address the role of Fra-2 in B cell differentiation. Deletion of Fra-2 leads to impaired B cell proliferation in the bone marrow. In addition, IL-7-stimulated pro-B cell cultures revealed a reduced differentiation from large pre-B cells to small B cells and immature B cells. Gene profiling and chromatin immunoprecipitation sequencing analyses unraveled a transcriptional reduction of the transcription factors Foxo1, Irf4, Ikaros, and Aiolos in Fra-2-deficient B cells...
July 3, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28555080/deregulation-of-kinase-signaling-and-lymphoid-development-in-ebf1-pdgfrb-all-leukemogenesis
#16
S J Welsh, M L Churchman, M Togni, C G Mullighan, J Hagman
The chimeric fusion oncogene early B-cell factor 1-platelet-derived growth factor receptor-β (EBF1-PDGFRB) is a recurrent lesion observed in Philadelphia-like B-acute lymphoblastic leukemia (B-ALL) and is associated with particularly poor prognosis. While it is understood that this fusion activates tyrosine kinase signaling, the mechanisms of transformation and importance of perturbation of EBF1 activity remain unknown. EBF1 is a nuclear transcription factor required for normal B-lineage specification, commitment and development...
May 30, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28552951/common-variants-near-ikzf1-are-associated-with-primary-sj%C3%A3-gren-s-syndrome-in-han-chinese
#17
Susu Qu, Yang Du, Suhua Chang, Liyuan Guo, Kechi Fang, Yongzhe Li, Fengchun Zhang, Kunlin Zhang, Jing Wang
Primary Sjögren's syndrome (pSS) is a systematic autoimmune disease with evidence of genetic predisposition. The IKZF1 (IKAROS family zinc finger 1 (Ikaros)) gene is located at 7p12.2, encodes a transcription factor related to chromatin remodeling, regulates lymphocyte differentiation, and has been reported to be associated with some autoimmune diseases. However, there have been no reports of an association between IKZF1 and pSS. To investigate the possibility of an association between the IKZF1 locus and pSS, we selected two single nucleotide polymorphisms (SNPs) in the IKZF1 locus, rs4917129 and rs4917014, based on a detailed analysis of genome-wide association study (GWAS) data and performed genotyping in 665 Han Chinese pSS patients and 863 healthy controls...
2017: PloS One
https://www.readbyqxmd.com/read/28529614/irf4-mum1-expression-is-associated-with-poor-survival-outcomes-in-patients-with-peripheral-t-cell-lymphoma
#18
Mi Hwa Heo, Ha Young Park, Young Hyeh Ko, Won Seog Kim, Seok Jin Kim
Background: Interferon regulatory factor 4 (IRF4)/multiple myeloma oncogene-1 (MUM1) is a member of the interferon regulatory factor family of transcriptional factors. Although IRF4/MUM1 expression is associated with aggressiveness of B-cell lymphoma and multiple myeloma, the prognostic value of IRF4/MUM1 expression in peripheral T-cell lymphoma (PTCL) is unclear. Methods: We analyzed a tissue array from 69 patients diagnosed with PTCL. The expression levels of IRF4/MUM1 and associated proteins such as MYC and Ikaros were analyzed by immunohistochemistry...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28463873/transcriptional-circuits-in-b-cell-transformation
#19
Yeguang Hu, Toshimi Yoshida, Katia Georgopoulos
PURPOSE OF REVIEW: Loss of IKAROS in committed B cell precursors causes a block in differentiation while at the same time augments aberrant cellular properties, such as bone marrow stromal adhesion, self-renewal and resistance to glucocorticoid-mediated cell death. B cell acute lymphoblastic leukaemias originating from these early stages of B cell differentiation and associated with IKAROS mutations share a high-risk cellular phenotype suggesting that deregulation of IKAROS-based mechanisms cause a highly malignant disease process...
July 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28425720/a-cereblon-modulator-cc-220-with-improved-degradation-of-ikaros-and-aiolos
#20
Mary E Matyskiela, Weihong Zhang, Hon-Wah Man, George Muller, Godrej Khambatta, Frans Baculi, Matthew Hickman, Laurie LeBrun, Barbra Pagarigan, Gilles Carmel, Chin-Chun Lu, Gang Lu, Mariko Riley, Yoshitaka Satoh, Peter Schafer, Thomas O Daniel, James Carmichael, Brian E Cathers, Philip P Chamberlain
The drugs lenalidomide and pomalidomide bind to the protein cereblon, directing the CRL4-CRBN E3 ligase toward the transcription factors Ikaros and Aiolos to cause their ubiquitination and degradation. Here we describe CC-220 (compound 6), a cereblon modulator in clinical development for systemic lupus erythematosis and relapsed/refractory multiple myeloma. Compound 6 binds cereblon with a higher affinity than lenalidomide or pomalidomide. Consistent with this, the cellular degradation of Ikaros and Aiolos is more potent and the extent of substrate depletion is greater...
April 20, 2017: Journal of Medicinal Chemistry
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