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https://www.readbyqxmd.com/read/29615403/sox11-augments-bcr-signaling-to-drive-mcl-like-tumor-development
#1
Pei-Yu Kuo, Shashidhar S Jatiani, Adeeb H Rahman, Donna Edwards, Zewei Jiang, Katya Ahr, Deepak Perumal, Violetta V Leshchenko, Joshua Brody, Rita Shaknovich, B Hilda Ye, Samir Parekh
Mantle cell lymphoma (MCL) is characterized by increased B-cell receptor (BCR) signaling and BTK inhibition is an effective therapeutic intervention in MCL patients. The mechanisms leading to increased BCR signaling in MCL are poorly understood, as mutations in upstream regulators of BCR signaling such as CD79A, commonly observed in other lymphomas, are rare in MCL. The transcription factor SOX11 is overexpressed in the majority (78-93%) of MCL patients and is considered an MCL-specific oncogene. So far, attempts to understand SOX11 function in vivo have been hampered by the lack of appropriate animal models; since germline deletion of SOX11 is embryonically lethal...
April 3, 2018: Blood
https://www.readbyqxmd.com/read/29545366/atlas-of-the-immune-cell-repertoire-in-mouse-atherosclerosis-defined-by-single-cell-rna-sequencing-and-mass-cytometry
#2
Holger Winkels, Erik Ehinger, Melanie Vassallo, Konrad Buscher, Huy Dinh, Kouji Kobiyama, Anouk Hamers, Clément Cochain, Ehsan Vafadarnejad, Antoine-Emmanuel Saliba, Alma Zernecke, Akula Pramod, Amlan Ghosh, Nathaly Anto Michel, Natalie Hoppe, Ingo Hilgendorf, Andreas Zirlik, Catherine Hedrick, Klaus Ley, Dennis Wolf
<u>Rationale:</u> Atherosclerosis is a chronic inflammatory disease that is driven by the interplay of pro- and anti-inflammatory leukocytes in the aorta. Yet, the phenotypic and transcriptional diversity of aortic leukocytes is only poorly understood. <u>Objective:</u> We characterized leukocytes from healthy and atherosclerotic mouse aortas in-depth by single cell RNA-sequencing (scRNAseq) and mass cytometry (CyTOF) to define an atlas of the immune cell landscape in atherosclerosis...
March 15, 2018: Circulation Research
https://www.readbyqxmd.com/read/29510697/distinct-predictive-biomarker-candidates-for-response-to-anti-ctla-4-and-anti-pd-1-immunotherapy-in-melanoma-patients
#3
Priyanka B Subrahmanyam, Zhiwan Dong, Daniel Gusenleitner, Anita Giobbie-Hurder, Mariano Severgnini, Jun Zhou, Michael Manos, Lauren M Eastman, Holden T Maecker, F Stephen Hodi
BACKGROUND: While immune checkpoint blockade has greatly improved clinical outcomes in diseases such as melanoma, there remains a need for predictive biomarkers to determine who will likely benefit most from which therapy. To date, most biomarkers of response have been identified in the tumors themselves. Biomarkers that could be assessed from peripheral blood would be even more desirable, because of ease of access and reproducibility of sampling. METHODS: We used mass cytometry (CyTOF) to comprehensively profile peripheral blood of melanoma patients, in order to find predictive biomarkers of response to anti-CTLA-4 or anti-PD-1 therapy...
March 6, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29507414/single-cell-mass-cytometry-reveals-distinct-populations-of-brain-myeloid-cells-in-mouse-neuroinflammation-and-neurodegeneration-models
#4
Bahareh Ajami, Nikolay Samusik, Peter Wieghofer, Peggy P Ho, Andrea Crotti, Zach Bjornson, Marco Prinz, Wendy J Fantl, Garry P Nolan, Lawrence Steinman
Neuroinflammation and neurodegeneration may represent two poles of brain pathology. Brain myeloid cells, particularly microglia, play key roles in these conditions. We employed single-cell mass cytometry (CyTOF) to compare myeloid cell populations in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis, the R6/2 model of Huntington's disease (HD) and the mutant superoxide dismutase 1 (mSOD1) model of amyotrophic lateral sclerosis (ALS). We identified three myeloid cell populations exclusive to the CNS and present in each disease model...
March 5, 2018: Nature Neuroscience
https://www.readbyqxmd.com/read/29490645/apatinib-exhibits-anti-leukemia-activity-in-preclinical-models-of-acute-lymphoblastic-leukemia
#5
Manman Deng, Jie Zha, Zhiwu Jiang, Xian Jia, Yuanfei Shi, Peng Li, Xiao Lei Chen, Zhihong Fang, Zhiqiang Du, Bing Xu
BACKGROUND: Acute lymphoblastic leukemia (ALL) is a clonal malignant disorder characterized by an uncontrolled proliferation of immature B or T lymphocytes. Extensive studies have suggested an involvement of angiogenesis signaling in ALL progression and resistance to treatment. Thus, targeting angiogenesis with anti-angiogenic drugs may be a promising approach for ALL treatment. In this study, we investigated the effectiveness of Apatinib, a novel receptor tyrosine kinase inhibitor selectively targeting VEGFR-2 in ALL cells...
February 28, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29476463/broad-immune-monitoring-and-profiling-of-t-cell-subsets-with-mass-cytometry
#6
Tess Melinda Brodie, Vinko Tosevski
Mass cytometry (cytometry by time-of-flight, CyTOF) is a high-dimensional single-cell analytical technology that allows for highly multiplexed measurements of protein or nucleic acid abundances by bringing together the detection capacity of atomic mass spectroscopy and the sample preparation workflow typical of regular flow cytometry. In 2014 the mass cytometer was adapted for the acquisition of samples from microscopy slides (termed imaging mass cytometry), greatly increasing the applicability of this technology with the inclusion of spatial information...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29466759/developmental-analysis-of-bone-marrow-neutrophils-reveals-populations-specialized-in-expansion-trafficking-and-effector-functions
#7
Maximilien Evrard, Immanuel W H Kwok, Shu Zhen Chong, Karen W W Teng, Etienne Becht, Jinmiao Chen, Je Lin Sieow, Hweixian Leong Penny, Goh Chi Ching, Sapna Devi, José Maria Adrover, Jackson L Y Li, Ka Hang Liong, Leonard Tan, Zhiyong Poon, Shihui Foo, Jia Wang Chua, I-Hsin Su, Karl Balabanian, Françoise Bachelerie, Subhra K Biswas, Anis Larbi, William Y K Hwang, Vikas Madan, H Phillip Koeffler, Siew Cheng Wong, Evan W Newell, Andrés Hidalgo, Florent Ginhoux, Lai Guan Ng
Neutrophils are specialized innate cells that require constant replenishment from proliferative bone marrow (BM) precursors as a result of their short half-life. Although it is established that neutrophils are derived from the granulocyte-macrophage progenitor (GMP), the differentiation pathways from GMP to functional mature neutrophils are poorly defined. Using mass cytometry (CyTOF) and cell-cycle-based analysis, we identified three neutrophil subsets within the BM: a committed proliferative neutrophil precursor (preNeu) which differentiates into non-proliferating immature neutrophils and mature neutrophils...
February 20, 2018: Immunity
https://www.readbyqxmd.com/read/29463558/disruption-of-wnt-%C3%AE-catenin-exerts-antileukemia-activity-and-synergizes-with-flt3-inhibition-in-flt3-mutant-acute-myeloid-leukemia
#8
Xuejie Jiang, Po Yee Mak, Hong Mu, Wenjing Tao, Duncan H Mak, Steven Kornblau, Qi Zhang, Peter Ruvolo, Jared K Burks, Weiguo Zhang, Teresa McQueen, Rongqing Pan, Hongsheng Zhou, Marina Konopleva, Jorge Cortes, Qifa Liu, Michael Andreeff, Bing Z Carter
Purpose: Wnt/β-catenin signaling is required for leukemic stem cell function. FLT3 mutations are frequently observed in acute myeloid leukemia (AML). Anomalous FLT3 signaling increases β-catenin nuclear localization and transcriptional activity. FLT3 tyrosine kinase inhibitors (TKI) are used clinically to treat FLT3 -mutated AML patients, but with limited efficacy. We investigated the antileukemia activity of combined Wnt/β-catenin and FLT3 inhibition in FLT3 -mutant AML. Experimental Design: Wnt/β-catenin signaling was inhibited by the β-catenin/CBP antagonist C-82/PRI-724 or siRNAs, and FLT3 signaling by sorafenib or quizartinib...
February 20, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29444438/commonly-occurring-cell-subsets-in-high-grade-serous-ovarian-tumors-identified-by-single-cell-mass-cytometry
#9
Veronica D Gonzalez, Nikolay Samusik, Tiffany J Chen, Erica S Savig, Nima Aghaeepour, David A Quigley, Ying-Wen Huang, Valeria Giangarrà, Alexander D Borowsky, Neil E Hubbard, Shih-Yu Chen, Guojun Han, Alan Ashworth, Thomas J Kipps, Jonathan S Berek, Garry P Nolan, Wendy J Fantl
We have performed an in-depth single-cell phenotypic characterization of high-grade serous ovarian cancer (HGSOC) by multiparametric mass cytometry (CyTOF). Using a CyTOF antibody panel to interrogate features of HGSOC biology, combined with unsupervised computational analysis, we identified noteworthy cell types co-occurring across the tumors. In addition to a dominant cell subset, each tumor harbored rarer cell phenotypes. One such group co-expressed E-cadherin and vimentin (EV), suggesting their potential role in epithelial mesenchymal transition, which was substantiated by pairwise correlation analyses...
February 13, 2018: Cell Reports
https://www.readbyqxmd.com/read/29370157/mass-cytometry-analysis-of-immune-cells-in-the-brain
#10
Ben Korin, Tania Dubovik, Asya Rolls
Immune cells comprise a diverse and dynamic cell population that is responsible for a broad range of immunological activities. They act in concert with other immune and nonimmune cells via cytokine-mediated communication and direct cell-cell interactions. Understanding the complex immune network requires a broad characterization of its individual cellular components. This is especially relevant for the brain compartment, which is an active immunological site, composed of resident and infiltrating immune cells that affect brain development, tissue homeostasis and neuronal activity...
February 2018: Nature Protocols
https://www.readbyqxmd.com/read/29305968/alternatives-to-current-flow-cytometry-data-analysis-for-clinical-and-research-studies
#11
REVIEW
Carmen Gondhalekar, Bartek Rajwa, Valery Patsekin, Kathy Ragheb, Jennifer Sturgis, J Paul Robinson
Flow cytometry has well-established methods for data analysis based on traditional data collection techniques. These techniques typically involved manual insertion of tube samples into an instrument that, historically, could only measure 1-3 colors. The field has since evolved to incorporate new technologies for faster and highly automated sample preparation and data collection. For example, the use of microwell plates on benchtop instruments is now a standard on virtually every new instrument, and so users can easily accumulate multiple data sets quickly...
February 1, 2018: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/29281633/scalable-multi-sample-single-cell-data-analysis-by-partition-assisted-clustering-and-multiple-alignments-of-networks
#12
Ye Henry Li, Dangna Li, Nikolay Samusik, Xiaowei Wang, Leying Guan, Garry P Nolan, Wing Hung Wong
Mass cytometry (CyTOF) has greatly expanded the capability of cytometry. It is now easy to generate multiple CyTOF samples in a single study, with each sample containing single-cell measurement on 50 markers for more than hundreds of thousands of cells. Current methods do not adequately address the issues concerning combining multiple samples for subpopulation discovery, and these issues can be quickly and dramatically amplified with increasing number of samples. To overcome this limitation, we developed Partition-Assisted Clustering and Multiple Alignments of Networks (PAC-MAN) for the fast automatic identification of cell populations in CyTOF data closely matching that of expert manual-discovery, and for alignments between subpopulations across samples to define dataset-level cellular states...
December 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/29205767/atomic-mass-tag-of-bismuth-209-for-increasing-the-immunoassay-multiplexing-capacity-of-mass-cytometry
#13
Guojun Han, Shih-Yu Chen, Veronica D Gonzalez, Eli R Zunder, Wendy J Fantl, Garry P Nolan
Mass cytometry (or CyTOF) is an atomic mass spectrometry-based single-cell immunoassay technology, which has provided an increasingly systematic and sophisticated view in basic biological and clinical studies. Using elemental reporters composed of stable heavy metal isotopes, more than 50 cellular parameters are measured simultaneously. However, this current multiplexing does not meet the theoretical capability of CyTOF instrumentation with 135 detectable channels, primarily due to the limitation of available chemistries for conjugating elemental mass tags to affinity reagents...
December 2017: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
https://www.readbyqxmd.com/read/29175391/integrated-functional-and-mass-spectrometry-based-flow-cytometric-phenotyping-to-describe-the-immune-microenvironment-in-acute-myeloid-leukemia
#14
Adam J Lamble, Matthew Dietz, Ted Laderas, Shannon McWeeney, Evan F Lind
A hallmark of the development of cancer is its ability to avoid detection and elimination by the immune system. There are many identified mechanisms of this immune evasion that can be measured both phenotypically and functionally. Functional studies directly show the ability of the tumor microenvironment to suppress immune responses, typically measured as lymphocyte proliferation, cytokine production or killing ability. While a direct measurement of function is ideal, these assays require ex vivo activation which may not accurately mimic in vivo conditions...
February 2018: Journal of Immunological Methods
https://www.readbyqxmd.com/read/29174717/comparison-of-cytof-assays-across-sites-results-of-a-six-center-pilot-study
#15
Michael D Leipold, Gerlinde Obermoser, Craig Fenwick, Katja Kleinstuber, Narges Rashidi, John P McNevin, Allison N Nau, Lisa E Wagar, Virginie Rozot, Mark M Davis, Stephen DeRosa, Giuseppe Pantaleo, Thomas J Scriba, Bruce D Walker, Lars R Olsen, Holden T Maecker
For more than five years, high-dimensional mass cytometry has been employed to study immunology. However, these studies have typically been performed in one laboratory on one or few instruments. We present the results of a six-center study using healthy control human peripheral blood mononuclear cells (PBMCs) and commercially available reagents to test the intra-site and inter-site variation of mass cytometers and operators. We used prestained controls generated by the primary center as a reference to compare against samples stained at each individual center...
February 2018: Journal of Immunological Methods
https://www.readbyqxmd.com/read/29156825/targeting-p-selectin-blocks-neuroblastoma-growth
#16
Riitta Nolo, Shelley Herbrich, Arvind Rao, Patrick Zweidler-McKay, Sankaranarayanan Kannan, Vidya Gopalakrishnan
Selectins and their ligands have been implicated in tumor growth and progression in carcinomas, but their role in neuroblastoma has not been systematically examined. In the current study we evaluated L-, P- and E-selectin binding to neuroblastoma cells and the expression of some of their known ligands, namely CD44, CD24 and P-selectin glycoprotein ligand-1 (PSGL-1). Genetic loss of PSGL-1 or CD24 and pharmacological inhibition of P-selectin reduced P-selectin binding to neuroblastoma cells i n vitro . Targeting P-selectin using specific antibodies promoted a significant reduction in the growth of neuroblastoma tumors in vivo ...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29128078/applications-of-mass-cytometry-in-clinical-medicine-the-promise-and-perils-of-clinical-cytof
#17
REVIEW
Gregory K Behbehani
Mass cytometry is a novel technology similar to flow cytometry in which antibodies are tagged with heavy metal molecules rather than fluorophores and then detected with time-of-flight mass spectrometry. This enables measurement of up to 50 simultaneous parameters with no autofluorescent background and little or no spillover or required compensation. Mass cytometry has tremendous potential for the analysis of highly complex clinical samples for the diagnosis and monitoring of malignant and autoimmune disorders...
December 2017: Clinics in Laboratory Medicine
https://www.readbyqxmd.com/read/29093262/human-regulatory-t-cells-undergo-self-inflicted-damage-via-granzyme-pathways-upon-activation
#18
Esilida Sula Karreci, Siawosh K Eskandari, Farokh Dotiwala, Sujit K Routray, Ahmed T Kurdi, Jean Pierre Assaker, Pavlo Luckyanchykov, Albana B Mihali, Omar Maarouf, Thiago J Borges, Abdullah Alkhudhayri, Kruti R Patel, Amr Radwan, Irene Ghobrial, Martina McGrath, Anil Chandraker, Leonardo V Riella, Wassim Elyaman, Reza Abdi, Judy Lieberman, Jamil Azzi
Tregs hold great promise as a cellular therapy for multiple immunologically mediated diseases, given their ability to control immune responses. The success of such strategies depends on the expansion of healthy, suppressive Tregs ex vivo and in vivo following the transfer. In clinical studies, levels of transferred Tregs decline sharply in the blood within a few days of the transfer. Tregs have a high rate of apoptosis. Here, we describe a new mechanism of Treg self-inflicted damage. We show that granzymes A and -B (GrA and GrB), which are highly upregulated in human Tregs upon stimulation, leak out of cytotoxic granules to induce cleavage of cytoplasmic and nuclear substrates, precipitating apoptosis in target cells...
November 2, 2017: JCI Insight
https://www.readbyqxmd.com/read/29071674/mass-cytometry-assays-for-antigen-specific-t-cells-using-cytof
#19
Dongxia Lin, Holden T Maecker
T Cells specific for a single antigen tend to be rare, even after expansion of memory cells. They are commonly detected by in vitro stimulation with peptides or protein, followed by staining for intracellular cytokines. In this protocol, we use CyTOF® mass cytometry to collect single-cell data on a large number of cytokines/chemokines, as well as cell-surface proteins that characterize T cells and other immune cells. We also include a method for magnetic bead enrichment of antigen-stimulated T cells, based on their expression of CD154 and CD69...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29036374/gating-mass-cytometry-data-by-deep-learning
#20
Huamin Li, Uri Shaham, Kelly P Stanton, Yi Yao, Ruth R Montgomery, Yuval Kluger
Motivation: Mass cytometry or CyTOF is an emerging technology for high-dimensional multiparameter single cell analysis that overcomes many limitations of fluorescence-based flow cytometry. New methods for analyzing CyTOF data attempt to improve automation, scalability, performance and interpretation of data generated in large studies. Assigning individual cells into discrete groups of cell types (gating) involves time-consuming sequential manual steps, untenable for larger studies. Results: We introduce DeepCyTOF, a standardization approach for gating, based on deep learning techniques...
November 1, 2017: Bioinformatics
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