Memantine potentiates cytarabine-induced cell death of acute leukemia correlating with inhibition of Kv1.3 potassium channels, AKT and ERK1/2 signaling View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Theresa Lowinus, Florian H. Heidel, Tanima Bose, Subbaiah Chary Nimmagadda, Tina Schnöder, Clemens Cammann, Ingo Schmitz, Ulrike Seifert, Thomas Fischer, Burkhart Schraven, Ursula Bommhardt

ABSTRACT

BACKGROUND: Treatment of acute leukemia is challenging and long-lasting remissions are difficult to induce. Innovative therapy approaches aim to complement standard chemotherapy to improve drug efficacy and decrease toxicity. Promising new therapeutic targets in cancer therapy include voltage-gated Kv1.3 potassium channels, but their role in acute leukemia is unclear. We reported that Kv1.3 channels of lymphocytes are blocked by memantine, which is known as an antagonist of neuronal N-methyl-D-aspartate type glutamate receptors and clinically applied in therapy of advanced Alzheimer disease. Here we evaluated whether pharmacological targeting of Kv1.3 channels by memantine promotes cell death of acute leukemia cells induced by chemotherapeutic cytarabine. METHODS: We analyzed acute lymphoid (Jurkat, CEM) and myeloid (HL-60, Molm-13, OCI-AML-3) leukemia cell lines and patients' acute leukemic blasts after treatment with either drug alone or the combination of cytarabine and memantine. Patch-clamp analysis was performed to evaluate inhibition of Kv1.3 channels and membrane depolarization by memantine. Cell death was determined with propidium iodide, Annexin V and SYTOX staining and cytochrome C release assay. Molecular effects of memantine co-treatment on activation of Caspases, AKT, ERK1/2, and JNK signaling were analysed by Western blot. Kv1.3 channel expression in Jurkat cells was downregulated by shRNA. RESULTS: Our study demonstrates that memantine inhibits Kv1.3 channels of acute leukemia cells and in combination with cytarabine potentiates cell death of acute lymphoid and myeloid leukemia cell lines as well as primary leukemic blasts from acute leukemia patients. At molecular level, memantine co-application fosters concurrent inhibition of AKT, S6 and ERK1/2 and reinforces nuclear down-regulation of MYC, a common target of AKT and ERK1/2 signaling. In addition, it augments mitochondrial dysfunction resulting in enhanced cytochrome C release and activation of Caspase-9 and Caspase-3 leading to amplified apoptosis. CONCLUSIONS: Our study underlines inhibition of Kv1.3 channels as a therapeutic strategy in acute leukemia and proposes co-treatment with memantine, a licensed and safe drug, as a potential approach to promote cytarabine-based cell death of various subtypes of acute leukemia. More... »

PAGES

5

References to SciGraph publications

  • 2013-03. PI3K/mTOR inhibition upregulates NOTCH-MYC signalling leading to an impaired cytotoxic response in LEUKEMIA
  • 2009-12. Voltage-gated potassium channels as therapeutic targets in NATURE REVIEWS DRUG DISCOVERY
  • 2000-02. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling in NATURE
  • 2015-12. Outlook on PI3K/AKT/mTOR inhibition in acute leukemia in MOLECULAR AND CELLULAR THERAPIES
  • 2014-10. A NOTCH1-driven MYC enhancer promotes T cell development, transformation and acute lymphoblastic leukemia in NATURE MEDICINE
  • 2003-07. A new quantitative assay for cytochrome c release in apoptotic cells in CELL DEATH & DIFFERENTIATION
  • 2015-06. Epo-induced erythroid maturation is dependent on Plcγ1 signaling in CELL DEATH & DIFFERENTIATION
  • 2014-04. Targeting proliferation of chronic lymphocytic leukemia (CLL) cells through KCa3.1 blockade in LEUKEMIA
  • 2013-08. Clofazimine, Psora-4 and PAP-1, inhibitors of the potassium channel Kv1.3, as a new and selective therapeutic strategy in chronic lymphocytic leukemia in LEUKEMIA
  • 2009-09. Inhibition of MEK signaling enhances the ability of cytarabine to induce growth arrest and apoptosis of acute myelogenous leukemia cells in APOPTOSIS
  • 2008-04. Targeting survival cascades induced by activation of Ras/Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways for effective leukemia therapy in LEUKEMIA
  • 2014-12. NMDA-receptor antagonists block B-cell function but foster IL-10 production in BCR/CD40-activated B cells in CELL COMMUNICATION AND SIGNALING
  • 2011-07. Roles of the Ras/Raf/MEK/ERK pathway in leukemia therapy in LEUKEMIA
  • 2016-09. Ionic immune suppression within the tumour microenvironment limits T cell effector function in NATURE
  • 2002-09. HERG potassium channels are constitutively expressed in primary human acute myeloid leukemias and regulate cell proliferation of normal and leukemic hemopoietic progenitors in LEUKEMIA
  • 2014-07. Activation and repression by oncogenic MYC shape tumour-specific gene expression profiles in NATURE
  • 2013-07. A phase Ib GOELAMS study of the mTOR inhibitor RAD001 in association with chemotherapy for AML patients in first relapse in LEUKEMIA
  • 1998-01. Regulation of c-myc expression by Ras/Raf signalling in ONCOGENE
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/s12964-018-0317-z

    DOI

    http://dx.doi.org/10.1186/s12964-018-0317-z

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1111461200

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30651113


    Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
    Incoming Citations Browse incoming citations for this publication using opencitations.net

    JSON-LD is the canonical representation for SciGraph data.

    TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

    [
      {
        "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
        "about": [
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/0601", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Biochemistry and Cell Biology", 
            "type": "DefinedTerm"
          }, 
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/06", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Biological Sciences", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "alternateName": "University Medical Center Freiburg", 
              "id": "https://www.grid.ac/institutes/grid.7708.8", 
              "name": [
                "Institute of Molecular and Clinical Immunology, Health Campus Immunology, Infectiology and Inflammation (GC-I3), Otto-von-Guericke-University Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany", 
                "Present address: Department of Hematology, Oncology, and Stem Cell Transplantation, Faculty of Medicine, Freiburg University Medical Center, Freiburg, Germany"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Lowinus", 
            "givenName": "Theresa", 
            "id": "sg:person.0670553320.91", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0670553320.91"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Jena University Hospital", 
              "id": "https://www.grid.ac/institutes/grid.275559.9", 
              "name": [
                "Department of Hematology and Oncology, GC-I3, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany", 
                "Leibniz Institute on Aging, Fritz-Lipmann Institute, Jena, Germany", 
                "Innere Medizin II, Universit\u00e4tsklinikum Jena, Jena, Germany"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Heidel", 
            "givenName": "Florian H.", 
            "id": "sg:person.0775224107.14", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0775224107.14"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Ludwig Maximilian University of Munich", 
              "id": "https://www.grid.ac/institutes/grid.5252.0", 
              "name": [
                "Leibniz Institute of Neurobiology, Magdeburg, Germany", 
                "Present address: Institute for Clinical Neuroimmunology, Ludwigs-Maximilians-University, Munich, Germany"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Bose", 
            "givenName": "Tanima", 
            "id": "sg:person.0661574772.20", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0661574772.20"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Otto-von-Guericke University Magdeburg", 
              "id": "https://www.grid.ac/institutes/grid.5807.a", 
              "name": [
                "Department of Hematology and Oncology, GC-I3, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Nimmagadda", 
            "givenName": "Subbaiah Chary", 
            "id": "sg:person.0761232261.88", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0761232261.88"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Jena University Hospital", 
              "id": "https://www.grid.ac/institutes/grid.275559.9", 
              "name": [
                "Department of Hematology and Oncology, GC-I3, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany", 
                "Leibniz Institute on Aging, Fritz-Lipmann Institute, Jena, Germany", 
                "Innere Medizin II, Universit\u00e4tsklinikum Jena, Jena, Germany"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Schn\u00f6der", 
            "givenName": "Tina", 
            "id": "sg:person.01367450651.30", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01367450651.30"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "University of Greifswald", 
              "id": "https://www.grid.ac/institutes/grid.5603.0", 
              "name": [
                "Friedrich Loeffler Institute for Medical Microbiology, University Medicine Greifswald, Greifswald, Germany"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Cammann", 
            "givenName": "Clemens", 
            "id": "sg:person.01216207426.77", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01216207426.77"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Otto-von-Guericke University Magdeburg", 
              "id": "https://www.grid.ac/institutes/grid.5807.a", 
              "name": [
                "Institute of Molecular and Clinical Immunology, Health Campus Immunology, Infectiology and Inflammation (GC-I3), Otto-von-Guericke-University Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany", 
                "Systems-Oriented Immunology and Inflammation Research Group, Helmholtz Centre for Infection Research, Braunschweig, Germany"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Schmitz", 
            "givenName": "Ingo", 
            "id": "sg:person.0631167477.79", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0631167477.79"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "University of Greifswald", 
              "id": "https://www.grid.ac/institutes/grid.5603.0", 
              "name": [
                "Institute of Molecular and Clinical Immunology, Health Campus Immunology, Infectiology and Inflammation (GC-I3), Otto-von-Guericke-University Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany", 
                "Friedrich Loeffler Institute for Medical Microbiology, University Medicine Greifswald, Greifswald, Germany"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Seifert", 
            "givenName": "Ulrike", 
            "id": "sg:person.01016664360.85", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01016664360.85"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Otto-von-Guericke University Magdeburg", 
              "id": "https://www.grid.ac/institutes/grid.5807.a", 
              "name": [
                "Department of Hematology and Oncology, GC-I3, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Fischer", 
            "givenName": "Thomas", 
            "id": "sg:person.01060452153.34", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01060452153.34"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Otto-von-Guericke University Magdeburg", 
              "id": "https://www.grid.ac/institutes/grid.5807.a", 
              "name": [
                "Institute of Molecular and Clinical Immunology, Health Campus Immunology, Infectiology and Inflammation (GC-I3), Otto-von-Guericke-University Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany", 
                "Department of Immune Control, Helmholtz Centre for Infection Research, Braunschweig, Germany"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Schraven", 
            "givenName": "Burkhart", 
            "id": "sg:person.01370636464.48", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01370636464.48"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Otto-von-Guericke University Magdeburg", 
              "id": "https://www.grid.ac/institutes/grid.5807.a", 
              "name": [
                "Institute of Molecular and Clinical Immunology, Health Campus Immunology, Infectiology and Inflammation (GC-I3), Otto-von-Guericke-University Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Bommhardt", 
            "givenName": "Ursula", 
            "id": "sg:person.0666053245.30", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0666053245.30"
            ], 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "sg:pub.10.1038/leu.2013.56", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1000940192", 
              "https://doi.org/10.1038/leu.2013.56"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1158/0008-5472.can-08-4884", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1001521680"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/leu.2012.285", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1002522270", 
              "https://doi.org/10.1038/leu.2012.285"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1158/0008-5472.can-09-1947", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1003525343"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/s1470-2045(12)70234-6", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1003540392"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1158/0008-5472.can-11-3605", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1003924469"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1182/blood-2009-02-206722", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1005267010"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1158/0008-5472.can-14-1470", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1005725329"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/s0304-3959(02)00041-6", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1005943050"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/s0304-3959(02)00041-6", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1005943050"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.onc.1201520", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1006669082", 
              "https://doi.org/10.1038/sj.onc.1201520"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.onc.1201520", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1006669082", 
              "https://doi.org/10.1038/sj.onc.1201520"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature13473", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1007164137", 
              "https://doi.org/10.1038/nature13473"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/35000501", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1010898206", 
              "https://doi.org/10.1038/35000501"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/35000501", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1010898206", 
              "https://doi.org/10.1038/35000501"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/cdd.2014.186", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1011874443", 
              "https://doi.org/10.1038/cdd.2014.186"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/s12964-014-0075-5", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1012760378", 
              "https://doi.org/10.1186/s12964-014-0075-5"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/s12964-014-0075-5", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1012760378", 
              "https://doi.org/10.1186/s12964-014-0075-5"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1159/000430223", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1013054047"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.18632/oncotarget.1873", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1013364001"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.clim.2011.11.009", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1013529588"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1146/annurev-immunol-032414-112212", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1013735131"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nm.3665", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1014690315", 
              "https://doi.org/10.1038/nm.3665"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.2174/157015908783769671", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1018056640"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature19364", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1018334075", 
              "https://doi.org/10.1038/nature19364"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1182/blood-2006-02-003475", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1020442508"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1182/blood-2005-02-0734", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1020986765"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.advenzreg.2011.09.019", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1021651880"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1182/blood-2014-08-551499", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1021744066"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/leu.2011.66", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1023487175", 
              "https://doi.org/10.1038/leu.2011.66"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.bbamcr.2015.11.032", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1023741124"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.cdd.4401263", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1024155155", 
              "https://doi.org/10.1038/sj.cdd.4401263"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.cdd.4401263", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1024155155", 
              "https://doi.org/10.1038/sj.cdd.4401263"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.12703/p7-13", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1025420584"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.leu.2402572", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1026620474", 
              "https://doi.org/10.1038/sj.leu.2402572"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.leu.2402572", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1026620474", 
              "https://doi.org/10.1038/sj.leu.2402572"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1111/j.1600-065x.2009.00816.x", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1029288935"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1111/j.1600-065x.2009.00816.x", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1029288935"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nrd2983", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1029856772", 
              "https://doi.org/10.1038/nrd2983"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nrd2983", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1029856772", 
              "https://doi.org/10.1038/nrd2983"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1091/mbc.e06-04-0263", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1029949438"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1073/pnas.87.23.9411", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1030149168"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/leu.2014.37", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1030664559", 
              "https://doi.org/10.1038/leu.2014.37"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1158/1078-0432.ccr-09-0842", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1030837144"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s10495-009-0372-4", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1032214152", 
              "https://doi.org/10.1007/s10495-009-0372-4"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s10495-009-0372-4", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1032214152", 
              "https://doi.org/10.1007/s10495-009-0372-4"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s10495-009-0372-4", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1032214152", 
              "https://doi.org/10.1007/s10495-009-0372-4"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.18632/oncotarget.10777", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1035339496"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/leu.2013.17", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1035660563", 
              "https://doi.org/10.1038/leu.2013.17"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1101/gad.1712408", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1036721811"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1182/blood-2005-05-1935", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1038638628"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1182/blood-2011-04-346601", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1039293974"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1073/pnas.0804236105", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1041218977"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1074/jbc.m003941200", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1041985293"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1098/rstb.2013.0106", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1042996096"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1128/mcb.01273-13", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1043334621"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/leu.2008.27", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1044187998", 
              "https://doi.org/10.1038/leu.2008.27"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/s1388-1981(02)00297-4", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1044206717"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1074/jbc.m413548200", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1044208921"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/emmm.201200235", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1045330701"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1084/jem.20040789", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1049827361"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/s40591-015-0040-8", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1053468770", 
              "https://doi.org/10.1186/s40591-015-0040-8"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1158/0008-5472.can-16-2372", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1063216354"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1158/0008-5472.can-16-2372", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1063216354"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.17219/acem/22339", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1068302295"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.2174/092986712798992048", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1069162376"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.2174/092986712798992093", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1069162381"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.2174/13816128113199990032", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1069169336"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1074775060", 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.ccell.2017.03.003", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1084761015"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1021/acschemneuro.7b00270", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1090882789"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.3389/fphys.2018.00499", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1103875408"
            ], 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "2019-12", 
        "datePublishedReg": "2019-12-01", 
        "description": "BACKGROUND: Treatment of acute leukemia is challenging and long-lasting remissions are difficult to induce. Innovative therapy approaches aim to complement standard chemotherapy to improve drug efficacy and decrease toxicity. Promising new therapeutic targets in cancer therapy include voltage-gated Kv1.3 potassium channels, but their role in acute leukemia is unclear. We reported that Kv1.3 channels of lymphocytes are blocked by memantine, which is known as an antagonist of neuronal N-methyl-D-aspartate type glutamate receptors and clinically applied in therapy of advanced Alzheimer disease. Here we evaluated whether pharmacological targeting of Kv1.3 channels by memantine promotes cell death of acute leukemia cells induced by chemotherapeutic cytarabine.\nMETHODS: We analyzed acute lymphoid (Jurkat, CEM) and myeloid (HL-60, Molm-13, OCI-AML-3) leukemia cell lines and patients' acute leukemic blasts after treatment with either drug alone or the combination of cytarabine and memantine. Patch-clamp analysis was performed to evaluate inhibition of Kv1.3 channels and membrane depolarization by memantine. Cell death was determined with propidium iodide, Annexin V and SYTOX staining and cytochrome C release assay. Molecular effects of memantine co-treatment on activation of Caspases, AKT, ERK1/2, and JNK signaling were analysed by Western blot. Kv1.3 channel expression in Jurkat cells was downregulated by shRNA.\nRESULTS: Our study demonstrates that memantine inhibits Kv1.3 channels of acute leukemia cells and in combination with cytarabine potentiates cell death of acute lymphoid and myeloid leukemia cell lines as well as primary leukemic blasts from acute leukemia patients. At molecular level, memantine co-application fosters concurrent inhibition of AKT, S6 and ERK1/2 and reinforces nuclear down-regulation of MYC, a common target of AKT and ERK1/2 signaling. In addition, it augments mitochondrial dysfunction resulting in enhanced cytochrome C release and activation of Caspase-9 and Caspase-3 leading to amplified apoptosis.\nCONCLUSIONS: Our study underlines inhibition of Kv1.3 channels as a therapeutic strategy in acute leukemia and proposes co-treatment with memantine, a licensed and safe drug, as a potential approach to promote cytarabine-based cell death of various subtypes of acute leukemia.", 
        "genre": "research_article", 
        "id": "sg:pub.10.1186/s12964-018-0317-z", 
        "inLanguage": [
          "en"
        ], 
        "isAccessibleForFree": true, 
        "isPartOf": [
          {
            "id": "sg:journal.1032046", 
            "issn": [
              "1478-811X"
            ], 
            "name": "Cell Communication and Signaling", 
            "type": "Periodical"
          }, 
          {
            "issueNumber": "1", 
            "type": "PublicationIssue"
          }, 
          {
            "type": "PublicationVolume", 
            "volumeNumber": "17"
          }
        ], 
        "name": "Memantine potentiates cytarabine-induced cell death of acute leukemia correlating with inhibition of Kv1.3 potassium channels, AKT and ERK1/2 signaling", 
        "pagination": "5", 
        "productId": [
          {
            "name": "readcube_id", 
            "type": "PropertyValue", 
            "value": [
              "d64c6994a72c7b66321843fb0b1117f889de28115d3b281f7587a66dcc48ef6c"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "30651113"
            ]
          }, 
          {
            "name": "nlm_unique_id", 
            "type": "PropertyValue", 
            "value": [
              "101170464"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1186/s12964-018-0317-z"
            ]
          }, 
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1111461200"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1186/s12964-018-0317-z", 
          "https://app.dimensions.ai/details/publication/pub.1111461200"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2019-04-11T11:11", 
        "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
        "sdPublisher": {
          "name": "Springer Nature - SN SciGraph project", 
          "type": "Organization"
        }, 
        "sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000353_0000000353/records_45354_00000002.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "https://link.springer.com/10.1186%2Fs12964-018-0317-z"
      }
    ]
     

    Download the RDF metadata as:  json-ld nt turtle xml License info

    HOW TO GET THIS DATA PROGRAMMATICALLY:

    JSON-LD is a popular format for linked data which is fully compatible with JSON.

    curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1186/s12964-018-0317-z'

    N-Triples is a line-based linked data format ideal for batch operations.

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1186/s12964-018-0317-z'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1186/s12964-018-0317-z'

    RDF/XML is a standard XML format for linked data.

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1186/s12964-018-0317-z'


     

    This table displays all metadata directly associated to this object as RDF triples.

    358 TRIPLES      21 PREDICATES      90 URIs      21 LITERALS      9 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1186/s12964-018-0317-z schema:about anzsrc-for:06
    2 anzsrc-for:0601
    3 schema:author Nfcb31ff5cd3a4d0fa13d37dd6080343b
    4 schema:citation sg:pub.10.1007/s10495-009-0372-4
    5 sg:pub.10.1038/35000501
    6 sg:pub.10.1038/cdd.2014.186
    7 sg:pub.10.1038/leu.2008.27
    8 sg:pub.10.1038/leu.2011.66
    9 sg:pub.10.1038/leu.2012.285
    10 sg:pub.10.1038/leu.2013.17
    11 sg:pub.10.1038/leu.2013.56
    12 sg:pub.10.1038/leu.2014.37
    13 sg:pub.10.1038/nature13473
    14 sg:pub.10.1038/nature19364
    15 sg:pub.10.1038/nm.3665
    16 sg:pub.10.1038/nrd2983
    17 sg:pub.10.1038/sj.cdd.4401263
    18 sg:pub.10.1038/sj.leu.2402572
    19 sg:pub.10.1038/sj.onc.1201520
    20 sg:pub.10.1186/s12964-014-0075-5
    21 sg:pub.10.1186/s40591-015-0040-8
    22 https://app.dimensions.ai/details/publication/pub.1074775060
    23 https://doi.org/10.1002/emmm.201200235
    24 https://doi.org/10.1016/j.advenzreg.2011.09.019
    25 https://doi.org/10.1016/j.bbamcr.2015.11.032
    26 https://doi.org/10.1016/j.ccell.2017.03.003
    27 https://doi.org/10.1016/j.clim.2011.11.009
    28 https://doi.org/10.1016/s0304-3959(02)00041-6
    29 https://doi.org/10.1016/s1388-1981(02)00297-4
    30 https://doi.org/10.1016/s1470-2045(12)70234-6
    31 https://doi.org/10.1021/acschemneuro.7b00270
    32 https://doi.org/10.1073/pnas.0804236105
    33 https://doi.org/10.1073/pnas.87.23.9411
    34 https://doi.org/10.1074/jbc.m003941200
    35 https://doi.org/10.1074/jbc.m413548200
    36 https://doi.org/10.1084/jem.20040789
    37 https://doi.org/10.1091/mbc.e06-04-0263
    38 https://doi.org/10.1098/rstb.2013.0106
    39 https://doi.org/10.1101/gad.1712408
    40 https://doi.org/10.1111/j.1600-065x.2009.00816.x
    41 https://doi.org/10.1128/mcb.01273-13
    42 https://doi.org/10.1146/annurev-immunol-032414-112212
    43 https://doi.org/10.1158/0008-5472.can-08-4884
    44 https://doi.org/10.1158/0008-5472.can-09-1947
    45 https://doi.org/10.1158/0008-5472.can-11-3605
    46 https://doi.org/10.1158/0008-5472.can-14-1470
    47 https://doi.org/10.1158/0008-5472.can-16-2372
    48 https://doi.org/10.1158/1078-0432.ccr-09-0842
    49 https://doi.org/10.1159/000430223
    50 https://doi.org/10.1182/blood-2005-02-0734
    51 https://doi.org/10.1182/blood-2005-05-1935
    52 https://doi.org/10.1182/blood-2006-02-003475
    53 https://doi.org/10.1182/blood-2009-02-206722
    54 https://doi.org/10.1182/blood-2011-04-346601
    55 https://doi.org/10.1182/blood-2014-08-551499
    56 https://doi.org/10.12703/p7-13
    57 https://doi.org/10.17219/acem/22339
    58 https://doi.org/10.18632/oncotarget.10777
    59 https://doi.org/10.18632/oncotarget.1873
    60 https://doi.org/10.2174/092986712798992048
    61 https://doi.org/10.2174/092986712798992093
    62 https://doi.org/10.2174/13816128113199990032
    63 https://doi.org/10.2174/157015908783769671
    64 https://doi.org/10.3389/fphys.2018.00499
    65 schema:datePublished 2019-12
    66 schema:datePublishedReg 2019-12-01
    67 schema:description BACKGROUND: Treatment of acute leukemia is challenging and long-lasting remissions are difficult to induce. Innovative therapy approaches aim to complement standard chemotherapy to improve drug efficacy and decrease toxicity. Promising new therapeutic targets in cancer therapy include voltage-gated Kv1.3 potassium channels, but their role in acute leukemia is unclear. We reported that Kv1.3 channels of lymphocytes are blocked by memantine, which is known as an antagonist of neuronal N-methyl-D-aspartate type glutamate receptors and clinically applied in therapy of advanced Alzheimer disease. Here we evaluated whether pharmacological targeting of Kv1.3 channels by memantine promotes cell death of acute leukemia cells induced by chemotherapeutic cytarabine. METHODS: We analyzed acute lymphoid (Jurkat, CEM) and myeloid (HL-60, Molm-13, OCI-AML-3) leukemia cell lines and patients' acute leukemic blasts after treatment with either drug alone or the combination of cytarabine and memantine. Patch-clamp analysis was performed to evaluate inhibition of Kv1.3 channels and membrane depolarization by memantine. Cell death was determined with propidium iodide, Annexin V and SYTOX staining and cytochrome C release assay. Molecular effects of memantine co-treatment on activation of Caspases, AKT, ERK1/2, and JNK signaling were analysed by Western blot. Kv1.3 channel expression in Jurkat cells was downregulated by shRNA. RESULTS: Our study demonstrates that memantine inhibits Kv1.3 channels of acute leukemia cells and in combination with cytarabine potentiates cell death of acute lymphoid and myeloid leukemia cell lines as well as primary leukemic blasts from acute leukemia patients. At molecular level, memantine co-application fosters concurrent inhibition of AKT, S6 and ERK1/2 and reinforces nuclear down-regulation of MYC, a common target of AKT and ERK1/2 signaling. In addition, it augments mitochondrial dysfunction resulting in enhanced cytochrome C release and activation of Caspase-9 and Caspase-3 leading to amplified apoptosis. CONCLUSIONS: Our study underlines inhibition of Kv1.3 channels as a therapeutic strategy in acute leukemia and proposes co-treatment with memantine, a licensed and safe drug, as a potential approach to promote cytarabine-based cell death of various subtypes of acute leukemia.
    68 schema:genre research_article
    69 schema:inLanguage en
    70 schema:isAccessibleForFree true
    71 schema:isPartOf N484911857e0a4fd7953ee73bc9c10e1f
    72 N9d2d7c50fc5a43029664cf2727f116ce
    73 sg:journal.1032046
    74 schema:name Memantine potentiates cytarabine-induced cell death of acute leukemia correlating with inhibition of Kv1.3 potassium channels, AKT and ERK1/2 signaling
    75 schema:pagination 5
    76 schema:productId Nb5d62852178e45f6a6a902dd653df9ca
    77 Nb7b4283df351438f94c83817b1a7719f
    78 Nbc96833ebb63496c8ccdb64707c38d5c
    79 Nfc0c6d5a67ab43d2bcd64ec95257764a
    80 Nfefb51a7ae674df2a37b54562098ae52
    81 schema:sameAs https://app.dimensions.ai/details/publication/pub.1111461200
    82 https://doi.org/10.1186/s12964-018-0317-z
    83 schema:sdDatePublished 2019-04-11T11:11
    84 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    85 schema:sdPublisher N8aa978c80f564810adf300a17bc8eabd
    86 schema:url https://link.springer.com/10.1186%2Fs12964-018-0317-z
    87 sgo:license sg:explorer/license/
    88 sgo:sdDataset articles
    89 rdf:type schema:ScholarlyArticle
    90 N1cdff4c822b043a7a276fa1a28836923 rdf:first sg:person.0666053245.30
    91 rdf:rest rdf:nil
    92 N255b8973deaf492da423d4b1a36c3544 rdf:first sg:person.0631167477.79
    93 rdf:rest N6e350de611844ae9872934567ce72343
    94 N30afc561c0e746d5a96fe3e1eee55ff2 rdf:first sg:person.0761232261.88
    95 rdf:rest N956385f091454376bec994f5901a5b9c
    96 N393572c17ad440919a4223ed2d1413b9 rdf:first sg:person.01370636464.48
    97 rdf:rest N1cdff4c822b043a7a276fa1a28836923
    98 N39bc2004390b4d9ea227e743434d4522 rdf:first sg:person.0661574772.20
    99 rdf:rest N30afc561c0e746d5a96fe3e1eee55ff2
    100 N484911857e0a4fd7953ee73bc9c10e1f schema:issueNumber 1
    101 rdf:type schema:PublicationIssue
    102 N68078d1761bc499783ae0f450317182c rdf:first sg:person.01060452153.34
    103 rdf:rest N393572c17ad440919a4223ed2d1413b9
    104 N6e350de611844ae9872934567ce72343 rdf:first sg:person.01016664360.85
    105 rdf:rest N68078d1761bc499783ae0f450317182c
    106 N8aa978c80f564810adf300a17bc8eabd schema:name Springer Nature - SN SciGraph project
    107 rdf:type schema:Organization
    108 N956385f091454376bec994f5901a5b9c rdf:first sg:person.01367450651.30
    109 rdf:rest Nc51c510ddfc544348123aee0fd66d8b3
    110 N9ce4232b7bcd41b6bba3fe349d4e4683 rdf:first sg:person.0775224107.14
    111 rdf:rest N39bc2004390b4d9ea227e743434d4522
    112 N9d2d7c50fc5a43029664cf2727f116ce schema:volumeNumber 17
    113 rdf:type schema:PublicationVolume
    114 Nb5d62852178e45f6a6a902dd653df9ca schema:name readcube_id
    115 schema:value d64c6994a72c7b66321843fb0b1117f889de28115d3b281f7587a66dcc48ef6c
    116 rdf:type schema:PropertyValue
    117 Nb7b4283df351438f94c83817b1a7719f schema:name dimensions_id
    118 schema:value pub.1111461200
    119 rdf:type schema:PropertyValue
    120 Nbc96833ebb63496c8ccdb64707c38d5c schema:name pubmed_id
    121 schema:value 30651113
    122 rdf:type schema:PropertyValue
    123 Nc51c510ddfc544348123aee0fd66d8b3 rdf:first sg:person.01216207426.77
    124 rdf:rest N255b8973deaf492da423d4b1a36c3544
    125 Nfc0c6d5a67ab43d2bcd64ec95257764a schema:name doi
    126 schema:value 10.1186/s12964-018-0317-z
    127 rdf:type schema:PropertyValue
    128 Nfcb31ff5cd3a4d0fa13d37dd6080343b rdf:first sg:person.0670553320.91
    129 rdf:rest N9ce4232b7bcd41b6bba3fe349d4e4683
    130 Nfefb51a7ae674df2a37b54562098ae52 schema:name nlm_unique_id
    131 schema:value 101170464
    132 rdf:type schema:PropertyValue
    133 anzsrc-for:06 schema:inDefinedTermSet anzsrc-for:
    134 schema:name Biological Sciences
    135 rdf:type schema:DefinedTerm
    136 anzsrc-for:0601 schema:inDefinedTermSet anzsrc-for:
    137 schema:name Biochemistry and Cell Biology
    138 rdf:type schema:DefinedTerm
    139 sg:journal.1032046 schema:issn 1478-811X
    140 schema:name Cell Communication and Signaling
    141 rdf:type schema:Periodical
    142 sg:person.01016664360.85 schema:affiliation https://www.grid.ac/institutes/grid.5603.0
    143 schema:familyName Seifert
    144 schema:givenName Ulrike
    145 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01016664360.85
    146 rdf:type schema:Person
    147 sg:person.01060452153.34 schema:affiliation https://www.grid.ac/institutes/grid.5807.a
    148 schema:familyName Fischer
    149 schema:givenName Thomas
    150 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01060452153.34
    151 rdf:type schema:Person
    152 sg:person.01216207426.77 schema:affiliation https://www.grid.ac/institutes/grid.5603.0
    153 schema:familyName Cammann
    154 schema:givenName Clemens
    155 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01216207426.77
    156 rdf:type schema:Person
    157 sg:person.01367450651.30 schema:affiliation https://www.grid.ac/institutes/grid.275559.9
    158 schema:familyName Schnöder
    159 schema:givenName Tina
    160 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01367450651.30
    161 rdf:type schema:Person
    162 sg:person.01370636464.48 schema:affiliation https://www.grid.ac/institutes/grid.5807.a
    163 schema:familyName Schraven
    164 schema:givenName Burkhart
    165 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01370636464.48
    166 rdf:type schema:Person
    167 sg:person.0631167477.79 schema:affiliation https://www.grid.ac/institutes/grid.5807.a
    168 schema:familyName Schmitz
    169 schema:givenName Ingo
    170 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0631167477.79
    171 rdf:type schema:Person
    172 sg:person.0661574772.20 schema:affiliation https://www.grid.ac/institutes/grid.5252.0
    173 schema:familyName Bose
    174 schema:givenName Tanima
    175 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0661574772.20
    176 rdf:type schema:Person
    177 sg:person.0666053245.30 schema:affiliation https://www.grid.ac/institutes/grid.5807.a
    178 schema:familyName Bommhardt
    179 schema:givenName Ursula
    180 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0666053245.30
    181 rdf:type schema:Person
    182 sg:person.0670553320.91 schema:affiliation https://www.grid.ac/institutes/grid.7708.8
    183 schema:familyName Lowinus
    184 schema:givenName Theresa
    185 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0670553320.91
    186 rdf:type schema:Person
    187 sg:person.0761232261.88 schema:affiliation https://www.grid.ac/institutes/grid.5807.a
    188 schema:familyName Nimmagadda
    189 schema:givenName Subbaiah Chary
    190 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0761232261.88
    191 rdf:type schema:Person
    192 sg:person.0775224107.14 schema:affiliation https://www.grid.ac/institutes/grid.275559.9
    193 schema:familyName Heidel
    194 schema:givenName Florian H.
    195 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0775224107.14
    196 rdf:type schema:Person
    197 sg:pub.10.1007/s10495-009-0372-4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1032214152
    198 https://doi.org/10.1007/s10495-009-0372-4
    199 rdf:type schema:CreativeWork
    200 sg:pub.10.1038/35000501 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010898206
    201 https://doi.org/10.1038/35000501
    202 rdf:type schema:CreativeWork
    203 sg:pub.10.1038/cdd.2014.186 schema:sameAs https://app.dimensions.ai/details/publication/pub.1011874443
    204 https://doi.org/10.1038/cdd.2014.186
    205 rdf:type schema:CreativeWork
    206 sg:pub.10.1038/leu.2008.27 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044187998
    207 https://doi.org/10.1038/leu.2008.27
    208 rdf:type schema:CreativeWork
    209 sg:pub.10.1038/leu.2011.66 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023487175
    210 https://doi.org/10.1038/leu.2011.66
    211 rdf:type schema:CreativeWork
    212 sg:pub.10.1038/leu.2012.285 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002522270
    213 https://doi.org/10.1038/leu.2012.285
    214 rdf:type schema:CreativeWork
    215 sg:pub.10.1038/leu.2013.17 schema:sameAs https://app.dimensions.ai/details/publication/pub.1035660563
    216 https://doi.org/10.1038/leu.2013.17
    217 rdf:type schema:CreativeWork
    218 sg:pub.10.1038/leu.2013.56 schema:sameAs https://app.dimensions.ai/details/publication/pub.1000940192
    219 https://doi.org/10.1038/leu.2013.56
    220 rdf:type schema:CreativeWork
    221 sg:pub.10.1038/leu.2014.37 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030664559
    222 https://doi.org/10.1038/leu.2014.37
    223 rdf:type schema:CreativeWork
    224 sg:pub.10.1038/nature13473 schema:sameAs https://app.dimensions.ai/details/publication/pub.1007164137
    225 https://doi.org/10.1038/nature13473
    226 rdf:type schema:CreativeWork
    227 sg:pub.10.1038/nature19364 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018334075
    228 https://doi.org/10.1038/nature19364
    229 rdf:type schema:CreativeWork
    230 sg:pub.10.1038/nm.3665 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014690315
    231 https://doi.org/10.1038/nm.3665
    232 rdf:type schema:CreativeWork
    233 sg:pub.10.1038/nrd2983 schema:sameAs https://app.dimensions.ai/details/publication/pub.1029856772
    234 https://doi.org/10.1038/nrd2983
    235 rdf:type schema:CreativeWork
    236 sg:pub.10.1038/sj.cdd.4401263 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024155155
    237 https://doi.org/10.1038/sj.cdd.4401263
    238 rdf:type schema:CreativeWork
    239 sg:pub.10.1038/sj.leu.2402572 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026620474
    240 https://doi.org/10.1038/sj.leu.2402572
    241 rdf:type schema:CreativeWork
    242 sg:pub.10.1038/sj.onc.1201520 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006669082
    243 https://doi.org/10.1038/sj.onc.1201520
    244 rdf:type schema:CreativeWork
    245 sg:pub.10.1186/s12964-014-0075-5 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012760378
    246 https://doi.org/10.1186/s12964-014-0075-5
    247 rdf:type schema:CreativeWork
    248 sg:pub.10.1186/s40591-015-0040-8 schema:sameAs https://app.dimensions.ai/details/publication/pub.1053468770
    249 https://doi.org/10.1186/s40591-015-0040-8
    250 rdf:type schema:CreativeWork
    251 https://app.dimensions.ai/details/publication/pub.1074775060 schema:CreativeWork
    252 https://doi.org/10.1002/emmm.201200235 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045330701
    253 rdf:type schema:CreativeWork
    254 https://doi.org/10.1016/j.advenzreg.2011.09.019 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021651880
    255 rdf:type schema:CreativeWork
    256 https://doi.org/10.1016/j.bbamcr.2015.11.032 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023741124
    257 rdf:type schema:CreativeWork
    258 https://doi.org/10.1016/j.ccell.2017.03.003 schema:sameAs https://app.dimensions.ai/details/publication/pub.1084761015
    259 rdf:type schema:CreativeWork
    260 https://doi.org/10.1016/j.clim.2011.11.009 schema:sameAs https://app.dimensions.ai/details/publication/pub.1013529588
    261 rdf:type schema:CreativeWork
    262 https://doi.org/10.1016/s0304-3959(02)00041-6 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005943050
    263 rdf:type schema:CreativeWork
    264 https://doi.org/10.1016/s1388-1981(02)00297-4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044206717
    265 rdf:type schema:CreativeWork
    266 https://doi.org/10.1016/s1470-2045(12)70234-6 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003540392
    267 rdf:type schema:CreativeWork
    268 https://doi.org/10.1021/acschemneuro.7b00270 schema:sameAs https://app.dimensions.ai/details/publication/pub.1090882789
    269 rdf:type schema:CreativeWork
    270 https://doi.org/10.1073/pnas.0804236105 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041218977
    271 rdf:type schema:CreativeWork
    272 https://doi.org/10.1073/pnas.87.23.9411 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030149168
    273 rdf:type schema:CreativeWork
    274 https://doi.org/10.1074/jbc.m003941200 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041985293
    275 rdf:type schema:CreativeWork
    276 https://doi.org/10.1074/jbc.m413548200 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044208921
    277 rdf:type schema:CreativeWork
    278 https://doi.org/10.1084/jem.20040789 schema:sameAs https://app.dimensions.ai/details/publication/pub.1049827361
    279 rdf:type schema:CreativeWork
    280 https://doi.org/10.1091/mbc.e06-04-0263 schema:sameAs https://app.dimensions.ai/details/publication/pub.1029949438
    281 rdf:type schema:CreativeWork
    282 https://doi.org/10.1098/rstb.2013.0106 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042996096
    283 rdf:type schema:CreativeWork
    284 https://doi.org/10.1101/gad.1712408 schema:sameAs https://app.dimensions.ai/details/publication/pub.1036721811
    285 rdf:type schema:CreativeWork
    286 https://doi.org/10.1111/j.1600-065x.2009.00816.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1029288935
    287 rdf:type schema:CreativeWork
    288 https://doi.org/10.1128/mcb.01273-13 schema:sameAs https://app.dimensions.ai/details/publication/pub.1043334621
    289 rdf:type schema:CreativeWork
    290 https://doi.org/10.1146/annurev-immunol-032414-112212 schema:sameAs https://app.dimensions.ai/details/publication/pub.1013735131
    291 rdf:type schema:CreativeWork
    292 https://doi.org/10.1158/0008-5472.can-08-4884 schema:sameAs https://app.dimensions.ai/details/publication/pub.1001521680
    293 rdf:type schema:CreativeWork
    294 https://doi.org/10.1158/0008-5472.can-09-1947 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003525343
    295 rdf:type schema:CreativeWork
    296 https://doi.org/10.1158/0008-5472.can-11-3605 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003924469
    297 rdf:type schema:CreativeWork
    298 https://doi.org/10.1158/0008-5472.can-14-1470 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005725329
    299 rdf:type schema:CreativeWork
    300 https://doi.org/10.1158/0008-5472.can-16-2372 schema:sameAs https://app.dimensions.ai/details/publication/pub.1063216354
    301 rdf:type schema:CreativeWork
    302 https://doi.org/10.1158/1078-0432.ccr-09-0842 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030837144
    303 rdf:type schema:CreativeWork
    304 https://doi.org/10.1159/000430223 schema:sameAs https://app.dimensions.ai/details/publication/pub.1013054047
    305 rdf:type schema:CreativeWork
    306 https://doi.org/10.1182/blood-2005-02-0734 schema:sameAs https://app.dimensions.ai/details/publication/pub.1020986765
    307 rdf:type schema:CreativeWork
    308 https://doi.org/10.1182/blood-2005-05-1935 schema:sameAs https://app.dimensions.ai/details/publication/pub.1038638628
    309 rdf:type schema:CreativeWork
    310 https://doi.org/10.1182/blood-2006-02-003475 schema:sameAs https://app.dimensions.ai/details/publication/pub.1020442508
    311 rdf:type schema:CreativeWork
    312 https://doi.org/10.1182/blood-2009-02-206722 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005267010
    313 rdf:type schema:CreativeWork
    314 https://doi.org/10.1182/blood-2011-04-346601 schema:sameAs https://app.dimensions.ai/details/publication/pub.1039293974
    315 rdf:type schema:CreativeWork
    316 https://doi.org/10.1182/blood-2014-08-551499 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021744066
    317 rdf:type schema:CreativeWork
    318 https://doi.org/10.12703/p7-13 schema:sameAs https://app.dimensions.ai/details/publication/pub.1025420584
    319 rdf:type schema:CreativeWork
    320 https://doi.org/10.17219/acem/22339 schema:sameAs https://app.dimensions.ai/details/publication/pub.1068302295
    321 rdf:type schema:CreativeWork
    322 https://doi.org/10.18632/oncotarget.10777 schema:sameAs https://app.dimensions.ai/details/publication/pub.1035339496
    323 rdf:type schema:CreativeWork
    324 https://doi.org/10.18632/oncotarget.1873 schema:sameAs https://app.dimensions.ai/details/publication/pub.1013364001
    325 rdf:type schema:CreativeWork
    326 https://doi.org/10.2174/092986712798992048 schema:sameAs https://app.dimensions.ai/details/publication/pub.1069162376
    327 rdf:type schema:CreativeWork
    328 https://doi.org/10.2174/092986712798992093 schema:sameAs https://app.dimensions.ai/details/publication/pub.1069162381
    329 rdf:type schema:CreativeWork
    330 https://doi.org/10.2174/13816128113199990032 schema:sameAs https://app.dimensions.ai/details/publication/pub.1069169336
    331 rdf:type schema:CreativeWork
    332 https://doi.org/10.2174/157015908783769671 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018056640
    333 rdf:type schema:CreativeWork
    334 https://doi.org/10.3389/fphys.2018.00499 schema:sameAs https://app.dimensions.ai/details/publication/pub.1103875408
    335 rdf:type schema:CreativeWork
    336 https://www.grid.ac/institutes/grid.275559.9 schema:alternateName Jena University Hospital
    337 schema:name Department of Hematology and Oncology, GC-I3, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany
    338 Innere Medizin II, Universitätsklinikum Jena, Jena, Germany
    339 Leibniz Institute on Aging, Fritz-Lipmann Institute, Jena, Germany
    340 rdf:type schema:Organization
    341 https://www.grid.ac/institutes/grid.5252.0 schema:alternateName Ludwig Maximilian University of Munich
    342 schema:name Leibniz Institute of Neurobiology, Magdeburg, Germany
    343 Present address: Institute for Clinical Neuroimmunology, Ludwigs-Maximilians-University, Munich, Germany
    344 rdf:type schema:Organization
    345 https://www.grid.ac/institutes/grid.5603.0 schema:alternateName University of Greifswald
    346 schema:name Friedrich Loeffler Institute for Medical Microbiology, University Medicine Greifswald, Greifswald, Germany
    347 Institute of Molecular and Clinical Immunology, Health Campus Immunology, Infectiology and Inflammation (GC-I3), Otto-von-Guericke-University Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany
    348 rdf:type schema:Organization
    349 https://www.grid.ac/institutes/grid.5807.a schema:alternateName Otto-von-Guericke University Magdeburg
    350 schema:name Department of Hematology and Oncology, GC-I3, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany
    351 Department of Immune Control, Helmholtz Centre for Infection Research, Braunschweig, Germany
    352 Institute of Molecular and Clinical Immunology, Health Campus Immunology, Infectiology and Inflammation (GC-I3), Otto-von-Guericke-University Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany
    353 Systems-Oriented Immunology and Inflammation Research Group, Helmholtz Centre for Infection Research, Braunschweig, Germany
    354 rdf:type schema:Organization
    355 https://www.grid.ac/institutes/grid.7708.8 schema:alternateName University Medical Center Freiburg
    356 schema:name Institute of Molecular and Clinical Immunology, Health Campus Immunology, Infectiology and Inflammation (GC-I3), Otto-von-Guericke-University Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany
    357 Present address: Department of Hematology, Oncology, and Stem Cell Transplantation, Faculty of Medicine, Freiburg University Medical Center, Freiburg, Germany
    358 rdf:type schema:Organization
     




    Preview window. Press ESC to close (or click here)


    ...