Sensitization of glioblastoma tumor micro-environment to chemo- and immunotherapy by Galectin-1 intranasal knock-down strategy View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-04-27

AUTHORS

Matthias Van Woensel, Thomas Mathivet, Nathalie Wauthoz, Rémi Rosière, Abhishek D. Garg, Patrizia Agostinis, Véronique Mathieu, Robert Kiss, Florence Lefranc, Louis Boon, Jochen Belmans, Stefaan W. Van Gool, Holger Gerhardt, Karim Amighi, Steven De Vleeschouwer

ABSTRACT

In this study, we evaluated the consequences of reducing Galectin-1 (Gal-1) in the tumor micro-environment (TME) of glioblastoma multiforme (GBM), via nose-to-brain transport. Gal-1 is overexpressed in GBM and drives chemo- and immunotherapy resistance. To promote nose-to-brain transport, we designed siRNA targeting Gal-1 (siGal-1) loaded chitosan nanoparticles that silence Gal-1 in the TME. Intranasal siGal-1 delivery induces a remarkable switch in the TME composition, with reduced myeloid suppressor cells and regulatory T cells, and increased CD4+ and CD8+ T cells. Gal-1 knock-down reduces macrophages’ polarization switch from M1 (pro-inflammatory) to M2 (anti-inflammatory) during GBM progression. These changes are accompanied by normalization of the tumor vasculature and increased survival for tumor bearing mice. The combination of siGal-1 treatment with temozolomide or immunotherapy (dendritic cell vaccination and PD-1 blocking) displays synergistic effects, increasing the survival of tumor bearing mice. Moreover, we could confirm the role of Gal-1 on lymphocytes in GBM patients by matching the Gal-1 expression and their T cell signatures. These findings indicate that intranasal siGal-1 nanoparticle delivery could be a valuable adjuvant treatment to increase the efficiency of immune-checkpoint blockade and chemotherapy. More... »

PAGES

1217

References to SciGraph publications

  • 2015-07-20. The prognostic landscape of genes and infiltrating immune cells across human cancers in NATURE MEDICINE
  • 1995-12. Apoptosis of T cells mediated by galectin-1 in NATURE
  • 2013-05-31. Low-dose temozolomide before dendritic-cell vaccination reduces (specifically) CD4+CD25++Foxp3+ regulatory T-cells in advanced melanoma patients in JOURNAL OF TRANSLATIONAL MEDICINE
  • 2012-05-14. Galectin-1, a gene preferentially expressed at the tumor margin, promotes glioblastoma cell invasion in MOLECULAR CANCER
  • 1997-11. Issues in experimental design and endpoint analysis in the study of experimental cytotoxic agents in vivo in breast cancer and other models in BREAST CANCER RESEARCH AND TREATMENT
  • 2012-05-08. Stratification according to HGG-IMMUNO RPA model predicts outcome in a large group of patients with relapsed malignant glioma treated by adjuvant postoperative dendritic cell vaccination in CANCER IMMUNOLOGY, IMMUNOTHERAPY
  • 2011-06-01. Principles and mechanisms of vessel normalization for cancer and other angiogenic diseases in NATURE REVIEWS DRUG DISCOVERY
  • 2016-05-09. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary in ACTA NEUROPATHOLOGICA
  • 2008-11-13. γH2AX and cancer in NATURE REVIEWS CANCER
  • 2016-02-19. Immunogenic versus tolerogenic phagocytosis during anticancer therapy: mechanisms and clinical translation in CELL DEATH & DIFFERENTIATION
  • 2004-08-22. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival in NATURE MEDICINE
  • 2008-09-04. Comprehensive genomic characterization defines human glioblastoma genes and core pathways in NATURE
  • 2010-04-18. Efficacy of monoterpene perillyl alcohol upon survival rate of patients with recurrent glioblastoma in JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
  • 2009-05. Turning 'sweet' on immunity: galectin–glycan interactions in immune tolerance and inflammation in NATURE REVIEWS IMMUNOLOGY
  • 2013-07-04. Altered galectin-1 serum levels in patients diagnosed with high-grade glioma in JOURNAL OF NEURO-ONCOLOGY
  • Journal

    TITLE

    Scientific Reports

    ISSUE

    1

    VOLUME

    7

    Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41598-017-01279-1

    DOI

    http://dx.doi.org/10.1038/s41598-017-01279-1

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1085072702

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/28450700


    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/2008/11", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Medical and Health Sciences", 
            "type": "DefinedTerm"
          }, 
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1107", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Immunology", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Administration, Intranasal", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Animals", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Disease Models, Animal", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Drug Therapy", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Galectin 1", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Gene Knockdown Techniques", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Glioblastoma", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Immunotherapy", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Mice", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "RNA, Small Interfering", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Treatment Outcome", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Tumor Microenvironment", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "alternateName": "Laboratoire de Pharmacie Gal\u00e9nique et de Biopharmacie, Universit\u00e9 libre de Bruxelles (ULB), Boulevard du triomphe CP207, 1050, Brussels, Belgium", 
              "id": "http://www.grid.ac/institutes/grid.4989.c", 
              "name": [
                "Research Group Experimental Neurosurgery and Neuroanatomy, KU Leuven, Herestraat 49, 3000, Leuven, Belgium", 
                "Laboratoire de Pharmacie Gal\u00e9nique et de Biopharmacie, Universit\u00e9 libre de Bruxelles (ULB), Boulevard du triomphe CP207, 1050, Brussels, Belgium"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Van Woensel", 
            "givenName": "Matthias", 
            "id": "sg:person.0733412002.24", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0733412002.24"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Vascular Patterning Laboratory Department of Oncology, KU Leuven, Herestraat 49 box 912, 3000, Leuven, Belgium", 
              "id": "http://www.grid.ac/institutes/grid.5596.f", 
              "name": [
                "Vascular Patterning Laboratory, VIB Center for Cancer Biology, VIB, Leuven, Belgium", 
                "Vascular Patterning Laboratory Department of Oncology, KU Leuven, Herestraat 49 box 912, 3000, Leuven, Belgium"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Mathivet", 
            "givenName": "Thomas", 
            "id": "sg:person.0771717213.50", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0771717213.50"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Laboratoire de Pharmacie Gal\u00e9nique et de Biopharmacie, Universit\u00e9 libre de Bruxelles (ULB), Boulevard du triomphe CP207, 1050, Brussels, Belgium", 
              "id": "http://www.grid.ac/institutes/grid.4989.c", 
              "name": [
                "Laboratoire de Pharmacie Gal\u00e9nique et de Biopharmacie, Universit\u00e9 libre de Bruxelles (ULB), Boulevard du triomphe CP207, 1050, Brussels, Belgium"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Wauthoz", 
            "givenName": "Nathalie", 
            "id": "sg:person.01075276203.91", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01075276203.91"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Laboratoire de Pharmacie Gal\u00e9nique et de Biopharmacie, Universit\u00e9 libre de Bruxelles (ULB), Boulevard du triomphe CP207, 1050, Brussels, Belgium", 
              "id": "http://www.grid.ac/institutes/grid.4989.c", 
              "name": [
                "Laboratoire de Pharmacie Gal\u00e9nique et de Biopharmacie, Universit\u00e9 libre de Bruxelles (ULB), Boulevard du triomphe CP207, 1050, Brussels, Belgium"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Rosi\u00e8re", 
            "givenName": "R\u00e9mi", 
            "id": "sg:person.01047640402.56", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01047640402.56"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Cell Death Research & Therapy (CDRT) Lab, Department of Cellular and Molecular Medicine, KU Leuven, Herestraat 49, Box 802, 3000, Leuven, Belgium", 
              "id": "http://www.grid.ac/institutes/grid.5596.f", 
              "name": [
                "Cell Death Research & Therapy (CDRT) Lab, Department of Cellular and Molecular Medicine, KU Leuven, Herestraat 49, Box 802, 3000, Leuven, Belgium"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Garg", 
            "givenName": "Abhishek D.", 
            "id": "sg:person.0610473103.37", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0610473103.37"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Cell Death Research & Therapy (CDRT) Lab, Department of Cellular and Molecular Medicine, KU Leuven, Herestraat 49, Box 802, 3000, Leuven, Belgium", 
              "id": "http://www.grid.ac/institutes/grid.5596.f", 
              "name": [
                "Cell Death Research & Therapy (CDRT) Lab, Department of Cellular and Molecular Medicine, KU Leuven, Herestraat 49, Box 802, 3000, Leuven, Belgium"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Agostinis", 
            "givenName": "Patrizia", 
            "id": "sg:person.01276463620.28", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01276463620.28"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Laboratoire de Canc\u00e9rologie et de Toxicologie Exp\u00e9rimentale, Universit\u00e9 libre de Bruxelles (ULB), Boulevard du triomphe CP205/01, 1050, Brussels, Belgium", 
              "id": "http://www.grid.ac/institutes/grid.4989.c", 
              "name": [
                "Laboratoire de Canc\u00e9rologie et de Toxicologie Exp\u00e9rimentale, Universit\u00e9 libre de Bruxelles (ULB), Boulevard du triomphe CP205/01, 1050, Brussels, Belgium"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Mathieu", 
            "givenName": "V\u00e9ronique", 
            "id": "sg:person.01106222733.88", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01106222733.88"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Laboratoire de Canc\u00e9rologie et de Toxicologie Exp\u00e9rimentale, Universit\u00e9 libre de Bruxelles (ULB), Boulevard du triomphe CP205/01, 1050, Brussels, Belgium", 
              "id": "http://www.grid.ac/institutes/grid.4989.c", 
              "name": [
                "Laboratoire de Canc\u00e9rologie et de Toxicologie Exp\u00e9rimentale, Universit\u00e9 libre de Bruxelles (ULB), Boulevard du triomphe CP205/01, 1050, Brussels, Belgium"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Kiss", 
            "givenName": "Robert", 
            "id": "sg:person.0755060624.17", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0755060624.17"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Neurosurgery, Erasmus University Hospitals, Route de Lennik 808-1070, 1050, Brussels, Belgium", 
              "id": "http://www.grid.ac/institutes/None", 
              "name": [
                "Department of Neurosurgery, Erasmus University Hospitals, Route de Lennik 808-1070, 1050, Brussels, Belgium"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Lefranc", 
            "givenName": "Florence", 
            "id": "sg:person.01141124405.14", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01141124405.14"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "EPIRUS Biopharmaceuticals, BV, Yalelaan 46, 3584, Utrecht, The Netherlands", 
              "id": "http://www.grid.ac/institutes/None", 
              "name": [
                "EPIRUS Biopharmaceuticals, BV, Yalelaan 46, 3584, Utrecht, The Netherlands"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Boon", 
            "givenName": "Louis", 
            "id": "sg:person.01230717016.18", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01230717016.18"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Laboratory of Pediatric Immunology, KU Leuven, Herestraat 49 box 811, 3000, Leuven, Belgium", 
              "id": "http://www.grid.ac/institutes/grid.5596.f", 
              "name": [
                "Laboratory of Pediatric Immunology, KU Leuven, Herestraat 49 box 811, 3000, Leuven, Belgium"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Belmans", 
            "givenName": "Jochen", 
            "id": "sg:person.0752540447.02", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0752540447.02"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Medizinische Leitung der Translationalen Onkologie, Immunologisches Onkologisches Zentrum, K\u00f6ln, Germany", 
              "id": "http://www.grid.ac/institutes/None", 
              "name": [
                "Medizinische Leitung der Translationalen Onkologie, Immunologisches Onkologisches Zentrum, K\u00f6ln, Germany"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Van Gool", 
            "givenName": "Stefaan W.", 
            "id": "sg:person.01075371674.61", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01075371674.61"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Vascular Patterning Laboratory Department of Oncology, KU Leuven, Herestraat 49 box 912, 3000, Leuven, Belgium", 
              "id": "http://www.grid.ac/institutes/grid.5596.f", 
              "name": [
                "Vascular Patterning Laboratory, VIB Center for Cancer Biology, VIB, Leuven, Belgium", 
                "Vascular Patterning Laboratory Department of Oncology, KU Leuven, Herestraat 49 box 912, 3000, Leuven, Belgium"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Gerhardt", 
            "givenName": "Holger", 
            "id": "sg:person.0754535466.06", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0754535466.06"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Laboratoire de Pharmacie Gal\u00e9nique et de Biopharmacie, Universit\u00e9 libre de Bruxelles (ULB), Boulevard du triomphe CP207, 1050, Brussels, Belgium", 
              "id": "http://www.grid.ac/institutes/grid.4989.c", 
              "name": [
                "Laboratoire de Pharmacie Gal\u00e9nique et de Biopharmacie, Universit\u00e9 libre de Bruxelles (ULB), Boulevard du triomphe CP207, 1050, Brussels, Belgium"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Amighi", 
            "givenName": "Karim", 
            "id": "sg:person.01035633305.19", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01035633305.19"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Neurosurgery, University Hospitals Leuven, Herestraat 49 box 7003, 3000, Leuven, Belgium", 
              "id": "http://www.grid.ac/institutes/grid.410569.f", 
              "name": [
                "Research Group Experimental Neurosurgery and Neuroanatomy, KU Leuven, Herestraat 49, 3000, Leuven, Belgium", 
                "Department of Neurosurgery, University Hospitals Leuven, Herestraat 49 box 7003, 3000, Leuven, Belgium"
              ], 
              "type": "Organization"
            }, 
            "familyName": "De Vleeschouwer", 
            "givenName": "Steven", 
            "id": "sg:person.0714764112.15", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0714764112.15"
            ], 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "sg:pub.10.1007/s00432-010-0873-0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1019818688", 
              "https://doi.org/10.1007/s00432-010-0873-0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s00401-016-1545-1", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1021788062", 
              "https://doi.org/10.1007/s00401-016-1545-1"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1023/a:1005938428456", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1046368219", 
              "https://doi.org/10.1023/a:1005938428456"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nrc2523", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1034798234", 
              "https://doi.org/10.1038/nrc2523"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s11060-013-1201-8", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1008447864", 
              "https://doi.org/10.1007/s11060-013-1201-8"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/cdd.2016.5", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1028271848", 
              "https://doi.org/10.1038/cdd.2016.5"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature07385", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1039570773", 
              "https://doi.org/10.1038/nature07385"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/378736a0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1032719916", 
              "https://doi.org/10.1038/378736a0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nm.3909", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1037811895", 
              "https://doi.org/10.1038/nm.3909"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s00262-012-1271-z", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1017260088", 
              "https://doi.org/10.1007/s00262-012-1271-z"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/1476-4598-11-32", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1037524966", 
              "https://doi.org/10.1186/1476-4598-11-32"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nrd3455", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1014273520", 
              "https://doi.org/10.1038/nrd3455"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/1479-5876-11-135", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1009458477", 
              "https://doi.org/10.1186/1479-5876-11-135"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nm1093", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1012208897", 
              "https://doi.org/10.1038/nm1093"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nri2536", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1046628050", 
              "https://doi.org/10.1038/nri2536"
            ], 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "2017-04-27", 
        "datePublishedReg": "2017-04-27", 
        "description": "In this study, we evaluated the consequences of reducing Galectin-1 (Gal-1) in the tumor micro-environment (TME) of glioblastoma multiforme (GBM), via nose-to-brain transport. Gal-1 is overexpressed in GBM and drives chemo- and immunotherapy resistance. To promote nose-to-brain transport, we designed siRNA targeting Gal-1 (siGal-1) loaded chitosan nanoparticles that silence Gal-1 in the TME. Intranasal siGal-1 delivery induces a remarkable switch in the TME composition, with reduced myeloid suppressor cells and regulatory T cells, and increased CD4+ and CD8+ T cells. Gal-1 knock-down reduces macrophages\u2019 polarization switch from M1 (pro-inflammatory) to M2 (anti-inflammatory) during GBM progression. These changes are accompanied by normalization of the tumor vasculature and increased survival for tumor bearing mice. The combination of siGal-1 treatment with temozolomide or immunotherapy (dendritic cell vaccination and PD-1 blocking) displays synergistic effects, increasing the survival of tumor bearing mice. Moreover, we could confirm the role of Gal-1 on lymphocytes in GBM patients by matching the Gal-1 expression and their T cell signatures. These findings indicate that intranasal siGal-1 nanoparticle delivery could be a valuable adjuvant treatment to increase the efficiency of immune-checkpoint blockade and chemotherapy.", 
        "genre": "article", 
        "id": "sg:pub.10.1038/s41598-017-01279-1", 
        "isAccessibleForFree": true, 
        "isFundedItemOf": [
          {
            "id": "sg:grant.3791950", 
            "type": "MonetaryGrant"
          }
        ], 
        "isPartOf": [
          {
            "id": "sg:journal.1045337", 
            "issn": [
              "2045-2322"
            ], 
            "name": "Scientific Reports", 
            "publisher": "Springer Nature", 
            "type": "Periodical"
          }, 
          {
            "issueNumber": "1", 
            "type": "PublicationIssue"
          }, 
          {
            "type": "PublicationVolume", 
            "volumeNumber": "7"
          }
        ], 
        "keywords": [
          "tumor bearing mice", 
          "glioblastoma multiforme", 
          "Gal-1", 
          "brain transport", 
          "T cells", 
          "bearing mice", 
          "valuable adjuvant treatment", 
          "myeloid suppressor cells", 
          "regulatory T cells", 
          "immune checkpoint blockade", 
          "T-cell signature", 
          "Gal-1 expression", 
          "immunotherapy resistance", 
          "adjuvant treatment", 
          "suppressor cells", 
          "GBM patients", 
          "tumor micro environment", 
          "GBM progression", 
          "tumor vasculature", 
          "TME composition", 
          "cell signature", 
          "immunotherapy", 
          "galectin-1", 
          "mice", 
          "nanoparticle delivery", 
          "survival", 
          "treatment", 
          "nose", 
          "cells", 
          "delivery", 
          "CD8", 
          "CD4", 
          "chemotherapy", 
          "patients", 
          "intranasal", 
          "temozolomide", 
          "lymphocytes", 
          "blockade", 
          "tumors", 
          "multiforme", 
          "macrophages", 
          "progression", 
          "vasculature", 
          "sensitization", 
          "siRNA", 
          "TME", 
          "chitosan nanoparticles", 
          "synergistic effect", 
          "M1", 
          "expression", 
          "findings", 
          "chemo", 
          "normalization", 
          "micro environment", 
          "study", 
          "role", 
          "m2", 
          "effect", 
          "resistance", 
          "changes", 
          "combination", 
          "consequences", 
          "strategies", 
          "remarkable switch", 
          "transport", 
          "signatures", 
          "switch", 
          "composition", 
          "nanoparticles", 
          "polarization switch", 
          "efficiency"
        ], 
        "name": "Sensitization of glioblastoma tumor micro-environment to chemo- and immunotherapy by Galectin-1 intranasal knock-down strategy", 
        "pagination": "1217", 
        "productId": [
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1085072702"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1038/s41598-017-01279-1"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "28450700"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1038/s41598-017-01279-1", 
          "https://app.dimensions.ai/details/publication/pub.1085072702"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2022-10-01T06:43", 
        "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
        "sdPublisher": {
          "name": "Springer Nature - SN SciGraph project", 
          "type": "Organization"
        }, 
        "sdSource": "s3://com-springernature-scigraph/baseset/20221001/entities/gbq_results/article/article_731.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "https://doi.org/10.1038/s41598-017-01279-1"
      }
    ]
     

    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.10.1038/s41598-017-01279-1'

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

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/s41598-017-01279-1'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/s41598-017-01279-1'

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

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/s41598-017-01279-1'


     

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

    361 TRIPLES      21 PREDICATES      123 URIs      100 LITERALS      19 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1038/s41598-017-01279-1 schema:about N2d854186237b45c0bca1a3b328609208
    2 N3d59bb2632704b43b64e312ca905895a
    3 N3f7e049c945946b8be2bbec87847d528
    4 N416cb89539fe42c586e81377018b8106
    5 N7d1ede0ea6444f40b3df4dc27ca0ccbf
    6 N8fedf3bb8c0a4cb9ae3426abbc80422c
    7 N9a3698bf0c8d4703a06cfd43c553d091
    8 Na1a4d51f3965463eb0be59890c0dc0fd
    9 Nbb40cd104b0343d895a3266c09d238c9
    10 Ncec35f938aa94a228cb29ba5701d35cb
    11 Ndb5030867f4e42cab3a2eb9cdb0ec916
    12 Nf9fc73fb6cd449a7b3da54512aaad119
    13 anzsrc-for:11
    14 anzsrc-for:1107
    15 schema:author Ne09966f85ccb47f8b6503495db1deb85
    16 schema:citation sg:pub.10.1007/s00262-012-1271-z
    17 sg:pub.10.1007/s00401-016-1545-1
    18 sg:pub.10.1007/s00432-010-0873-0
    19 sg:pub.10.1007/s11060-013-1201-8
    20 sg:pub.10.1023/a:1005938428456
    21 sg:pub.10.1038/378736a0
    22 sg:pub.10.1038/cdd.2016.5
    23 sg:pub.10.1038/nature07385
    24 sg:pub.10.1038/nm.3909
    25 sg:pub.10.1038/nm1093
    26 sg:pub.10.1038/nrc2523
    27 sg:pub.10.1038/nrd3455
    28 sg:pub.10.1038/nri2536
    29 sg:pub.10.1186/1476-4598-11-32
    30 sg:pub.10.1186/1479-5876-11-135
    31 schema:datePublished 2017-04-27
    32 schema:datePublishedReg 2017-04-27
    33 schema:description In this study, we evaluated the consequences of reducing Galectin-1 (Gal-1) in the tumor micro-environment (TME) of glioblastoma multiforme (GBM), via nose-to-brain transport. Gal-1 is overexpressed in GBM and drives chemo- and immunotherapy resistance. To promote nose-to-brain transport, we designed siRNA targeting Gal-1 (siGal-1) loaded chitosan nanoparticles that silence Gal-1 in the TME. Intranasal siGal-1 delivery induces a remarkable switch in the TME composition, with reduced myeloid suppressor cells and regulatory T cells, and increased CD4+ and CD8+ T cells. Gal-1 knock-down reduces macrophages’ polarization switch from M1 (pro-inflammatory) to M2 (anti-inflammatory) during GBM progression. These changes are accompanied by normalization of the tumor vasculature and increased survival for tumor bearing mice. The combination of siGal-1 treatment with temozolomide or immunotherapy (dendritic cell vaccination and PD-1 blocking) displays synergistic effects, increasing the survival of tumor bearing mice. Moreover, we could confirm the role of Gal-1 on lymphocytes in GBM patients by matching the Gal-1 expression and their T cell signatures. These findings indicate that intranasal siGal-1 nanoparticle delivery could be a valuable adjuvant treatment to increase the efficiency of immune-checkpoint blockade and chemotherapy.
    34 schema:genre article
    35 schema:isAccessibleForFree true
    36 schema:isPartOf N08ff8e645ac84dd8b4dd418bb2b7907c
    37 N3fdc7576e3804644bc77cc11688da6ca
    38 sg:journal.1045337
    39 schema:keywords CD4
    40 CD8
    41 GBM patients
    42 GBM progression
    43 Gal-1
    44 Gal-1 expression
    45 M1
    46 T cells
    47 T-cell signature
    48 TME
    49 TME composition
    50 adjuvant treatment
    51 bearing mice
    52 blockade
    53 brain transport
    54 cell signature
    55 cells
    56 changes
    57 chemo
    58 chemotherapy
    59 chitosan nanoparticles
    60 combination
    61 composition
    62 consequences
    63 delivery
    64 effect
    65 efficiency
    66 expression
    67 findings
    68 galectin-1
    69 glioblastoma multiforme
    70 immune checkpoint blockade
    71 immunotherapy
    72 immunotherapy resistance
    73 intranasal
    74 lymphocytes
    75 m2
    76 macrophages
    77 mice
    78 micro environment
    79 multiforme
    80 myeloid suppressor cells
    81 nanoparticle delivery
    82 nanoparticles
    83 normalization
    84 nose
    85 patients
    86 polarization switch
    87 progression
    88 regulatory T cells
    89 remarkable switch
    90 resistance
    91 role
    92 sensitization
    93 siRNA
    94 signatures
    95 strategies
    96 study
    97 suppressor cells
    98 survival
    99 switch
    100 synergistic effect
    101 temozolomide
    102 transport
    103 treatment
    104 tumor bearing mice
    105 tumor micro environment
    106 tumor vasculature
    107 tumors
    108 valuable adjuvant treatment
    109 vasculature
    110 schema:name Sensitization of glioblastoma tumor micro-environment to chemo- and immunotherapy by Galectin-1 intranasal knock-down strategy
    111 schema:pagination 1217
    112 schema:productId N20fa03567c484c8da470a2cad610ad3b
    113 Nc102ac9d58ed47439bff0f21a8306fd1
    114 Ne49b3f34bc864602879bd8a28f2b82ac
    115 schema:sameAs https://app.dimensions.ai/details/publication/pub.1085072702
    116 https://doi.org/10.1038/s41598-017-01279-1
    117 schema:sdDatePublished 2022-10-01T06:43
    118 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    119 schema:sdPublisher N4af93f55f6d24fda90761f1218a39dc4
    120 schema:url https://doi.org/10.1038/s41598-017-01279-1
    121 sgo:license sg:explorer/license/
    122 sgo:sdDataset articles
    123 rdf:type schema:ScholarlyArticle
    124 N08ff8e645ac84dd8b4dd418bb2b7907c schema:issueNumber 1
    125 rdf:type schema:PublicationIssue
    126 N1145d86529e14af1af845ac7188dd933 rdf:first sg:person.01035633305.19
    127 rdf:rest N63a840c3538d4cd9b654ad4f60a4c393
    128 N1d1d6496b301424e804fbcc472e405d5 rdf:first sg:person.0754535466.06
    129 rdf:rest N1145d86529e14af1af845ac7188dd933
    130 N20fa03567c484c8da470a2cad610ad3b schema:name pubmed_id
    131 schema:value 28450700
    132 rdf:type schema:PropertyValue
    133 N253ff213a8a04aa1bd9b2f9efb6ef803 rdf:first sg:person.01075371674.61
    134 rdf:rest N1d1d6496b301424e804fbcc472e405d5
    135 N2987c1c5606c40b1a7b14caa5d4d6013 rdf:first sg:person.01106222733.88
    136 rdf:rest Na9d1ed9626764f45a5bc9794e6f81cbf
    137 N2d854186237b45c0bca1a3b328609208 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    138 schema:name RNA, Small Interfering
    139 rdf:type schema:DefinedTerm
    140 N3ccb7405f47e4f8fb3c1b2b4298a7ba4 rdf:first sg:person.01276463620.28
    141 rdf:rest N2987c1c5606c40b1a7b14caa5d4d6013
    142 N3d59bb2632704b43b64e312ca905895a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    143 schema:name Glioblastoma
    144 rdf:type schema:DefinedTerm
    145 N3f7e049c945946b8be2bbec87847d528 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    146 schema:name Galectin 1
    147 rdf:type schema:DefinedTerm
    148 N3fdc7576e3804644bc77cc11688da6ca schema:volumeNumber 7
    149 rdf:type schema:PublicationVolume
    150 N416cb89539fe42c586e81377018b8106 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    151 schema:name Disease Models, Animal
    152 rdf:type schema:DefinedTerm
    153 N4af93f55f6d24fda90761f1218a39dc4 schema:name Springer Nature - SN SciGraph project
    154 rdf:type schema:Organization
    155 N4ebf6c354dfa41eb82b0e09fc5d72718 rdf:first sg:person.01141124405.14
    156 rdf:rest N76d40fd15a11403aaa65ae400ca01c42
    157 N63a840c3538d4cd9b654ad4f60a4c393 rdf:first sg:person.0714764112.15
    158 rdf:rest rdf:nil
    159 N643eb1beca49439aa16a3c519927f1f6 rdf:first sg:person.0771717213.50
    160 rdf:rest Nb1f4a6e0daf84546b59b8b87bc4b01a4
    161 N76d40fd15a11403aaa65ae400ca01c42 rdf:first sg:person.01230717016.18
    162 rdf:rest Ne5f1c24a88df4163a5ef379467771562
    163 N7d1ede0ea6444f40b3df4dc27ca0ccbf schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    164 schema:name Animals
    165 rdf:type schema:DefinedTerm
    166 N8fedf3bb8c0a4cb9ae3426abbc80422c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    167 schema:name Administration, Intranasal
    168 rdf:type schema:DefinedTerm
    169 N95d808400a8e44c398e95e7086245ade rdf:first sg:person.0610473103.37
    170 rdf:rest N3ccb7405f47e4f8fb3c1b2b4298a7ba4
    171 N9a3698bf0c8d4703a06cfd43c553d091 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    172 schema:name Immunotherapy
    173 rdf:type schema:DefinedTerm
    174 Na1a4d51f3965463eb0be59890c0dc0fd schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    175 schema:name Tumor Microenvironment
    176 rdf:type schema:DefinedTerm
    177 Na9d1ed9626764f45a5bc9794e6f81cbf rdf:first sg:person.0755060624.17
    178 rdf:rest N4ebf6c354dfa41eb82b0e09fc5d72718
    179 Nb1f4a6e0daf84546b59b8b87bc4b01a4 rdf:first sg:person.01075276203.91
    180 rdf:rest Nc257f00435a04291884f7c531d599e44
    181 Nbb40cd104b0343d895a3266c09d238c9 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    182 schema:name Mice
    183 rdf:type schema:DefinedTerm
    184 Nc102ac9d58ed47439bff0f21a8306fd1 schema:name dimensions_id
    185 schema:value pub.1085072702
    186 rdf:type schema:PropertyValue
    187 Nc257f00435a04291884f7c531d599e44 rdf:first sg:person.01047640402.56
    188 rdf:rest N95d808400a8e44c398e95e7086245ade
    189 Ncec35f938aa94a228cb29ba5701d35cb schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    190 schema:name Drug Therapy
    191 rdf:type schema:DefinedTerm
    192 Ndb5030867f4e42cab3a2eb9cdb0ec916 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    193 schema:name Treatment Outcome
    194 rdf:type schema:DefinedTerm
    195 Ne09966f85ccb47f8b6503495db1deb85 rdf:first sg:person.0733412002.24
    196 rdf:rest N643eb1beca49439aa16a3c519927f1f6
    197 Ne49b3f34bc864602879bd8a28f2b82ac schema:name doi
    198 schema:value 10.1038/s41598-017-01279-1
    199 rdf:type schema:PropertyValue
    200 Ne5f1c24a88df4163a5ef379467771562 rdf:first sg:person.0752540447.02
    201 rdf:rest N253ff213a8a04aa1bd9b2f9efb6ef803
    202 Nf9fc73fb6cd449a7b3da54512aaad119 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    203 schema:name Gene Knockdown Techniques
    204 rdf:type schema:DefinedTerm
    205 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
    206 schema:name Medical and Health Sciences
    207 rdf:type schema:DefinedTerm
    208 anzsrc-for:1107 schema:inDefinedTermSet anzsrc-for:
    209 schema:name Immunology
    210 rdf:type schema:DefinedTerm
    211 sg:grant.3791950 http://pending.schema.org/fundedItem sg:pub.10.1038/s41598-017-01279-1
    212 rdf:type schema:MonetaryGrant
    213 sg:journal.1045337 schema:issn 2045-2322
    214 schema:name Scientific Reports
    215 schema:publisher Springer Nature
    216 rdf:type schema:Periodical
    217 sg:person.01035633305.19 schema:affiliation grid-institutes:grid.4989.c
    218 schema:familyName Amighi
    219 schema:givenName Karim
    220 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01035633305.19
    221 rdf:type schema:Person
    222 sg:person.01047640402.56 schema:affiliation grid-institutes:grid.4989.c
    223 schema:familyName Rosière
    224 schema:givenName Rémi
    225 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01047640402.56
    226 rdf:type schema:Person
    227 sg:person.01075276203.91 schema:affiliation grid-institutes:grid.4989.c
    228 schema:familyName Wauthoz
    229 schema:givenName Nathalie
    230 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01075276203.91
    231 rdf:type schema:Person
    232 sg:person.01075371674.61 schema:affiliation grid-institutes:None
    233 schema:familyName Van Gool
    234 schema:givenName Stefaan W.
    235 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01075371674.61
    236 rdf:type schema:Person
    237 sg:person.01106222733.88 schema:affiliation grid-institutes:grid.4989.c
    238 schema:familyName Mathieu
    239 schema:givenName Véronique
    240 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01106222733.88
    241 rdf:type schema:Person
    242 sg:person.01141124405.14 schema:affiliation grid-institutes:None
    243 schema:familyName Lefranc
    244 schema:givenName Florence
    245 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01141124405.14
    246 rdf:type schema:Person
    247 sg:person.01230717016.18 schema:affiliation grid-institutes:None
    248 schema:familyName Boon
    249 schema:givenName Louis
    250 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01230717016.18
    251 rdf:type schema:Person
    252 sg:person.01276463620.28 schema:affiliation grid-institutes:grid.5596.f
    253 schema:familyName Agostinis
    254 schema:givenName Patrizia
    255 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01276463620.28
    256 rdf:type schema:Person
    257 sg:person.0610473103.37 schema:affiliation grid-institutes:grid.5596.f
    258 schema:familyName Garg
    259 schema:givenName Abhishek D.
    260 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0610473103.37
    261 rdf:type schema:Person
    262 sg:person.0714764112.15 schema:affiliation grid-institutes:grid.410569.f
    263 schema:familyName De Vleeschouwer
    264 schema:givenName Steven
    265 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0714764112.15
    266 rdf:type schema:Person
    267 sg:person.0733412002.24 schema:affiliation grid-institutes:grid.4989.c
    268 schema:familyName Van Woensel
    269 schema:givenName Matthias
    270 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0733412002.24
    271 rdf:type schema:Person
    272 sg:person.0752540447.02 schema:affiliation grid-institutes:grid.5596.f
    273 schema:familyName Belmans
    274 schema:givenName Jochen
    275 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0752540447.02
    276 rdf:type schema:Person
    277 sg:person.0754535466.06 schema:affiliation grid-institutes:grid.5596.f
    278 schema:familyName Gerhardt
    279 schema:givenName Holger
    280 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0754535466.06
    281 rdf:type schema:Person
    282 sg:person.0755060624.17 schema:affiliation grid-institutes:grid.4989.c
    283 schema:familyName Kiss
    284 schema:givenName Robert
    285 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0755060624.17
    286 rdf:type schema:Person
    287 sg:person.0771717213.50 schema:affiliation grid-institutes:grid.5596.f
    288 schema:familyName Mathivet
    289 schema:givenName Thomas
    290 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0771717213.50
    291 rdf:type schema:Person
    292 sg:pub.10.1007/s00262-012-1271-z schema:sameAs https://app.dimensions.ai/details/publication/pub.1017260088
    293 https://doi.org/10.1007/s00262-012-1271-z
    294 rdf:type schema:CreativeWork
    295 sg:pub.10.1007/s00401-016-1545-1 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021788062
    296 https://doi.org/10.1007/s00401-016-1545-1
    297 rdf:type schema:CreativeWork
    298 sg:pub.10.1007/s00432-010-0873-0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1019818688
    299 https://doi.org/10.1007/s00432-010-0873-0
    300 rdf:type schema:CreativeWork
    301 sg:pub.10.1007/s11060-013-1201-8 schema:sameAs https://app.dimensions.ai/details/publication/pub.1008447864
    302 https://doi.org/10.1007/s11060-013-1201-8
    303 rdf:type schema:CreativeWork
    304 sg:pub.10.1023/a:1005938428456 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046368219
    305 https://doi.org/10.1023/a:1005938428456
    306 rdf:type schema:CreativeWork
    307 sg:pub.10.1038/378736a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1032719916
    308 https://doi.org/10.1038/378736a0
    309 rdf:type schema:CreativeWork
    310 sg:pub.10.1038/cdd.2016.5 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028271848
    311 https://doi.org/10.1038/cdd.2016.5
    312 rdf:type schema:CreativeWork
    313 sg:pub.10.1038/nature07385 schema:sameAs https://app.dimensions.ai/details/publication/pub.1039570773
    314 https://doi.org/10.1038/nature07385
    315 rdf:type schema:CreativeWork
    316 sg:pub.10.1038/nm.3909 schema:sameAs https://app.dimensions.ai/details/publication/pub.1037811895
    317 https://doi.org/10.1038/nm.3909
    318 rdf:type schema:CreativeWork
    319 sg:pub.10.1038/nm1093 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012208897
    320 https://doi.org/10.1038/nm1093
    321 rdf:type schema:CreativeWork
    322 sg:pub.10.1038/nrc2523 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034798234
    323 https://doi.org/10.1038/nrc2523
    324 rdf:type schema:CreativeWork
    325 sg:pub.10.1038/nrd3455 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014273520
    326 https://doi.org/10.1038/nrd3455
    327 rdf:type schema:CreativeWork
    328 sg:pub.10.1038/nri2536 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046628050
    329 https://doi.org/10.1038/nri2536
    330 rdf:type schema:CreativeWork
    331 sg:pub.10.1186/1476-4598-11-32 schema:sameAs https://app.dimensions.ai/details/publication/pub.1037524966
    332 https://doi.org/10.1186/1476-4598-11-32
    333 rdf:type schema:CreativeWork
    334 sg:pub.10.1186/1479-5876-11-135 schema:sameAs https://app.dimensions.ai/details/publication/pub.1009458477
    335 https://doi.org/10.1186/1479-5876-11-135
    336 rdf:type schema:CreativeWork
    337 grid-institutes:None schema:alternateName Department of Neurosurgery, Erasmus University Hospitals, Route de Lennik 808-1070, 1050, Brussels, Belgium
    338 EPIRUS Biopharmaceuticals, BV, Yalelaan 46, 3584, Utrecht, The Netherlands
    339 Medizinische Leitung der Translationalen Onkologie, Immunologisches Onkologisches Zentrum, Köln, Germany
    340 schema:name Department of Neurosurgery, Erasmus University Hospitals, Route de Lennik 808-1070, 1050, Brussels, Belgium
    341 EPIRUS Biopharmaceuticals, BV, Yalelaan 46, 3584, Utrecht, The Netherlands
    342 Medizinische Leitung der Translationalen Onkologie, Immunologisches Onkologisches Zentrum, Köln, Germany
    343 rdf:type schema:Organization
    344 grid-institutes:grid.410569.f schema:alternateName Department of Neurosurgery, University Hospitals Leuven, Herestraat 49 box 7003, 3000, Leuven, Belgium
    345 schema:name Department of Neurosurgery, University Hospitals Leuven, Herestraat 49 box 7003, 3000, Leuven, Belgium
    346 Research Group Experimental Neurosurgery and Neuroanatomy, KU Leuven, Herestraat 49, 3000, Leuven, Belgium
    347 rdf:type schema:Organization
    348 grid-institutes:grid.4989.c schema:alternateName Laboratoire de Cancérologie et de Toxicologie Expérimentale, Université libre de Bruxelles (ULB), Boulevard du triomphe CP205/01, 1050, Brussels, Belgium
    349 Laboratoire de Pharmacie Galénique et de Biopharmacie, Université libre de Bruxelles (ULB), Boulevard du triomphe CP207, 1050, Brussels, Belgium
    350 schema:name Laboratoire de Cancérologie et de Toxicologie Expérimentale, Université libre de Bruxelles (ULB), Boulevard du triomphe CP205/01, 1050, Brussels, Belgium
    351 Laboratoire de Pharmacie Galénique et de Biopharmacie, Université libre de Bruxelles (ULB), Boulevard du triomphe CP207, 1050, Brussels, Belgium
    352 Research Group Experimental Neurosurgery and Neuroanatomy, KU Leuven, Herestraat 49, 3000, Leuven, Belgium
    353 rdf:type schema:Organization
    354 grid-institutes:grid.5596.f schema:alternateName Cell Death Research & Therapy (CDRT) Lab, Department of Cellular and Molecular Medicine, KU Leuven, Herestraat 49, Box 802, 3000, Leuven, Belgium
    355 Laboratory of Pediatric Immunology, KU Leuven, Herestraat 49 box 811, 3000, Leuven, Belgium
    356 Vascular Patterning Laboratory Department of Oncology, KU Leuven, Herestraat 49 box 912, 3000, Leuven, Belgium
    357 schema:name Cell Death Research & Therapy (CDRT) Lab, Department of Cellular and Molecular Medicine, KU Leuven, Herestraat 49, Box 802, 3000, Leuven, Belgium
    358 Laboratory of Pediatric Immunology, KU Leuven, Herestraat 49 box 811, 3000, Leuven, Belgium
    359 Vascular Patterning Laboratory Department of Oncology, KU Leuven, Herestraat 49 box 912, 3000, Leuven, Belgium
    360 Vascular Patterning Laboratory, VIB Center for Cancer Biology, VIB, Leuven, Belgium
    361 rdf:type schema:Organization
     




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


    ...