Intrinsic fluorescence of the clinically approved multikinase inhibitor nintedanib reveals lysosomal sequestration as resistance mechanism in FGFR-driven lung cancer View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-12

AUTHORS

Bernhard Englinger, Sebastian Kallus, Julia Senkiv, Daniela Heilos, Lisa Gabler, Sushilla van Schoonhoven, Alessio Terenzi, Patrick Moser, Christine Pirker, Gerald Timelthaler, Walter Jäger, Christian R. Kowol, Petra Heffeter, Michael Grusch, Walter Berger

ABSTRACT

BACKGROUND: Studying the intracellular distribution of pharmacological agents, including anticancer compounds, is of central importance in biomedical research. It constitutes a prerequisite for a better understanding of the molecular mechanisms underlying drug action and resistance development. Hyperactivated fibroblast growth factor receptors (FGFRs) constitute a promising therapy target in several types of malignancies including lung cancer. The clinically approved small-molecule FGFR inhibitor nintedanib exerts strong cytotoxicity in FGFR-driven lung cancer cells. However, subcellular pharmacokinetics of this compound and its impact on therapeutic efficacy remain obscure. METHODS: 3-dimensional fluorescence spectroscopy was conducted to asses cell-free nintedanib fluorescence properties. MTT assay was used to determine the impact of the lysosome-targeting agents bafilomycin A1 and chloroquine combined with nintedanib on lung cancer cell viability. Flow cytometry and live cell as well as confocal microscopy were performed to analyze uptake kinetics as well as subcellular distribution of nintedanib. Western blot was conducted to investigate protein expression. Cryosections of subcutaneous tumor allografts were generated to detect intratumoral nintedanib in mice after oral drug administration. RESULTS: Here, we report for the first time drug-intrinsic fluorescence properties of nintedanib in living and fixed cancer cells as well as in cryosections derived from allograft tumors of orally treated mice. Using this feature in conjunction with flow cytometry and confocal microscopy allowed to determine cellular drug accumulation levels, impact of the ABCB1 efflux pump and to uncover nintedanib trapping into lysosomes. Lysosomal sequestration - resulting in an organelle-specific and pH-dependent nintedanib fluorescence - was identified as an intrinsic resistance mechanism in FGFR-driven lung cancer cells. Accordingly, combination of nintedanib with agents compromising lysosomal acidification (bafilomycin A1, chloroquine) exerted distinctly synergistic growth inhibitory effects. CONCLUSION: Our findings provide a powerful tool to dissect molecular factors impacting organismal and intracellular pharmacokinetics of nintedanib. Regarding clinical application, prevention of lysosomal trapping via lysosome-alkalization might represent a promising strategy to circumvent cancer cell-intrinsic nintedanib resistance. More... »

PAGES

122

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s13046-017-0592-3

DOI

http://dx.doi.org/10.1186/s13046-017-0592-3

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1091509957

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28882160


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/2008/1112", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Oncology and Carcinogenesis", 
        "type": "DefinedTerm"
      }, 
      {
        "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"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Animals", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Antineoplastic Combined Chemotherapy Protocols", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Cell Line, Tumor", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Cell Proliferation", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Drug Synergism", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Fluorescence", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Humans", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Indoles", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Lung", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Lung Neoplasms", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Lysosomes", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Macrolides", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Mice", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Phosphorylation", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Receptors, Fibroblast Growth Factor", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Signal Transduction", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Xenograft Model Antitumor Assays", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "Medical University of Vienna", 
          "id": "https://www.grid.ac/institutes/grid.22937.3d", 
          "name": [
            "Institute of Cancer Research and Comprehensive Cancer Center, Department of Medicine I, Medical University of Vienna, Borschkegasse 8a, A-1090, Vienna, Austria"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Englinger", 
        "givenName": "Bernhard", 
        "id": "sg:person.0754665152.41", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0754665152.41"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Vienna", 
          "id": "https://www.grid.ac/institutes/grid.10420.37", 
          "name": [
            "Institute of Inorganic Chemistry, University of Vienna, Waehringer Str. 42, A-1090, Vienna, Austria", 
            "Research Cluster \u201cTranslational Cancer Therapy Research\u201d, University of Vienna, Waehringer Strasse 42, A-1090, Vienna, Austria"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Kallus", 
        "givenName": "Sebastian", 
        "id": "sg:person.015510741205.44", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.015510741205.44"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Institute of Cell Biology", 
          "id": "https://www.grid.ac/institutes/grid.466769.c", 
          "name": [
            "Institute of Cancer Research and Comprehensive Cancer Center, Department of Medicine I, Medical University of Vienna, Borschkegasse 8a, A-1090, Vienna, Austria", 
            "Institute of Cell Biology NAS of Ukraine, Drahomanova str 14/16, 79005, Lviv, Ukraine"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Senkiv", 
        "givenName": "Julia", 
        "id": "sg:person.01155541213.49", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01155541213.49"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Vienna", 
          "id": "https://www.grid.ac/institutes/grid.10420.37", 
          "name": [
            "Institute of Cancer Research and Comprehensive Cancer Center, Department of Medicine I, Medical University of Vienna, Borschkegasse 8a, A-1090, Vienna, Austria", 
            "Department of Pharmacology and Toxicology, University of Vienna, Althanstr. 14, 1090, Vienna, Austria"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Heilos", 
        "givenName": "Daniela", 
        "id": "sg:person.01214702556.78", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01214702556.78"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Medical University of Vienna", 
          "id": "https://www.grid.ac/institutes/grid.22937.3d", 
          "name": [
            "Institute of Cancer Research and Comprehensive Cancer Center, Department of Medicine I, Medical University of Vienna, Borschkegasse 8a, A-1090, Vienna, Austria"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Gabler", 
        "givenName": "Lisa", 
        "id": "sg:person.01223662745.79", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01223662745.79"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Medical University of Vienna", 
          "id": "https://www.grid.ac/institutes/grid.22937.3d", 
          "name": [
            "Institute of Cancer Research and Comprehensive Cancer Center, Department of Medicine I, Medical University of Vienna, Borschkegasse 8a, A-1090, Vienna, Austria"
          ], 
          "type": "Organization"
        }, 
        "familyName": "van Schoonhoven", 
        "givenName": "Sushilla", 
        "id": "sg:person.01174034333.95", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01174034333.95"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Vienna", 
          "id": "https://www.grid.ac/institutes/grid.10420.37", 
          "name": [
            "Institute of Inorganic Chemistry, University of Vienna, Waehringer Str. 42, A-1090, Vienna, Austria"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Terenzi", 
        "givenName": "Alessio", 
        "id": "sg:person.0614165067.34", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0614165067.34"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Medical University of Vienna", 
          "id": "https://www.grid.ac/institutes/grid.22937.3d", 
          "name": [
            "Institute of Cancer Research and Comprehensive Cancer Center, Department of Medicine I, Medical University of Vienna, Borschkegasse 8a, A-1090, Vienna, Austria"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Moser", 
        "givenName": "Patrick", 
        "id": "sg:person.016221256537.42", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016221256537.42"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Medical University of Vienna", 
          "id": "https://www.grid.ac/institutes/grid.22937.3d", 
          "name": [
            "Institute of Cancer Research and Comprehensive Cancer Center, Department of Medicine I, Medical University of Vienna, Borschkegasse 8a, A-1090, Vienna, Austria"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Pirker", 
        "givenName": "Christine", 
        "id": "sg:person.01225146250.81", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01225146250.81"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Medical University of Vienna", 
          "id": "https://www.grid.ac/institutes/grid.22937.3d", 
          "name": [
            "Institute of Cancer Research and Comprehensive Cancer Center, Department of Medicine I, Medical University of Vienna, Borschkegasse 8a, A-1090, Vienna, Austria"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Timelthaler", 
        "givenName": "Gerald", 
        "id": "sg:person.0674116056.53", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0674116056.53"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Vienna", 
          "id": "https://www.grid.ac/institutes/grid.10420.37", 
          "name": [
            "Department of Pharmaceutical Chemistry, Division of Clinical Pharmacy and Diagnostics, University of Vienna, Althanstrasse 14, A-1090, Vienna, Austria"
          ], 
          "type": "Organization"
        }, 
        "familyName": "J\u00e4ger", 
        "givenName": "Walter", 
        "id": "sg:person.0637641214.35", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0637641214.35"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Vienna", 
          "id": "https://www.grid.ac/institutes/grid.10420.37", 
          "name": [
            "Institute of Inorganic Chemistry, University of Vienna, Waehringer Str. 42, A-1090, Vienna, Austria", 
            "Research Cluster \u201cTranslational Cancer Therapy Research\u201d, University of Vienna, Waehringer Strasse 42, A-1090, Vienna, Austria"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Kowol", 
        "givenName": "Christian R.", 
        "id": "sg:person.01346501472.16", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01346501472.16"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Vienna", 
          "id": "https://www.grid.ac/institutes/grid.10420.37", 
          "name": [
            "Institute of Cancer Research and Comprehensive Cancer Center, Department of Medicine I, Medical University of Vienna, Borschkegasse 8a, A-1090, Vienna, Austria", 
            "Research Cluster \u201cTranslational Cancer Therapy Research\u201d, University of Vienna, Waehringer Strasse 42, A-1090, Vienna, Austria"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Heffeter", 
        "givenName": "Petra", 
        "id": "sg:person.01204222651.00", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01204222651.00"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Medical University of Vienna", 
          "id": "https://www.grid.ac/institutes/grid.22937.3d", 
          "name": [
            "Institute of Cancer Research and Comprehensive Cancer Center, Department of Medicine I, Medical University of Vienna, Borschkegasse 8a, A-1090, Vienna, Austria"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Grusch", 
        "givenName": "Michael", 
        "id": "sg:person.01124512740.04", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01124512740.04"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Vienna", 
          "id": "https://www.grid.ac/institutes/grid.10420.37", 
          "name": [
            "Institute of Cancer Research and Comprehensive Cancer Center, Department of Medicine I, Medical University of Vienna, Borschkegasse 8a, A-1090, Vienna, Austria", 
            "Research Cluster \u201cTranslational Cancer Therapy Research\u201d, University of Vienna, Waehringer Strasse 42, A-1090, Vienna, Austria"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Berger", 
        "givenName": "Walter", 
        "id": "sg:person.0735503622.07", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0735503622.07"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "https://doi.org/10.1016/j.jchromb.2015.08.032", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1001719307"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.phrs.2016.12.021", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1003591175"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.jchromb.2016.04.049", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1004636224"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1152/ajpcell.00462.2010", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1005635627"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/1078-0432.ccr-13-3060", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1009839645"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/med.21288", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1010892806"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.18632/oncotarget.2732", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1011489635"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.freeradbiomed.2016.04.201", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1014404203"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1517/14728222.2011.566217", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1014607436"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1039/c5cc06983a", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1015184058"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1517/13543776.2011.561784", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1017358753"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1529/biophysj.103.038422", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1017631680"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1038/emboj.2012.32", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1018656852"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/jm501562a", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1018667497"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/978-3-540-69494-6_3", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1018827762", 
          "https://doi.org/10.1007/978-3-540-69494-6_3"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.tiv.2010.12.010", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1019945857"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.ctrv.2016.03.015", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1022926671"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/0006-2952(74)90174-9", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1025224101"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/0006-2952(74)90174-9", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1025224101"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nrc2780", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1025760788", 
          "https://doi.org/10.1038/nrc2780"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nrc2780", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1025760788", 
          "https://doi.org/10.1038/nrc2780"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/0065-2571(84)90007-4", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1026371633"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/0065-2571(84)90007-4", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1026371633"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.drup.2015.11.004", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1027719327"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/1078-0432.ccr-14-2329", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1028097305"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/35067100", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1029980557", 
          "https://doi.org/10.1038/35067100"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/35067100", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1029980557", 
          "https://doi.org/10.1038/35067100"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/jcph.752", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1031999675"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nchem.1961", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1032194266", 
          "https://doi.org/10.1038/nchem.1961"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.semcdb.2015.10.012", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1033061162"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.bjc.6605642", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1034513961", 
          "https://doi.org/10.1038/sj.bjc.6605642"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.tips.2016.10.003", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1035581892"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1200/jco.2016.67.2048", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1036774524"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1200/jco.2016.67.2048", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1036774524"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1124/mol.114.097451", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1043604822"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s00249-008-0338-4", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1045739897", 
          "https://doi.org/10.1007/s00249-008-0338-4"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s00249-008-0338-4", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1045739897", 
          "https://doi.org/10.1007/s00249-008-0338-4"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/0008-5472.can-11-3654", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1046115607"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.semcdb.2015.12.014", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1047294719"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/0008-5472.can-11-3034", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1047723989"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1177/1753465815579608", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1048200583"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1177/1753465815579608", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1048200583"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.18632/oncotarget.10324", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1049478933"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.18632/oncotarget.10324", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1049478933"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/1078-0432.ccr-14-3212", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1063224838"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1177/1758834016630976", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1064077375"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1177/1758834016630976", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1064077375"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.15586/jkcvhl.2015.44", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1067984661"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.2174/1566524016666151222144231", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1069185368"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.3892/ijmm.2016.2620", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1071508496"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.3892/ijmm.2016.2620", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1071508496"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1077617215", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.ejps.2017.04.016", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1085119367"
        ], 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2017-12", 
    "datePublishedReg": "2017-12-01", 
    "description": "BACKGROUND: Studying the intracellular distribution of pharmacological agents, including anticancer compounds, is of central importance in biomedical research. It constitutes a prerequisite for a better understanding of the molecular mechanisms underlying drug action and resistance development. Hyperactivated fibroblast growth factor receptors (FGFRs) constitute a promising therapy target in several types of malignancies including lung cancer. The clinically approved small-molecule FGFR inhibitor nintedanib exerts strong cytotoxicity in FGFR-driven lung cancer cells. However, subcellular pharmacokinetics of this compound and its impact on therapeutic efficacy remain obscure.\nMETHODS: 3-dimensional fluorescence spectroscopy was conducted to asses cell-free nintedanib fluorescence properties. MTT assay was used to determine the impact of the lysosome-targeting agents bafilomycin A1 and chloroquine combined with nintedanib on lung cancer cell viability. Flow cytometry and live cell as well as confocal microscopy were performed to analyze uptake kinetics as well as subcellular distribution of nintedanib. Western blot was conducted to investigate protein expression. Cryosections of subcutaneous tumor allografts were generated to detect intratumoral nintedanib in mice after oral drug administration.\nRESULTS: Here, we report for the first time drug-intrinsic fluorescence properties of nintedanib in living and fixed cancer cells as well as in cryosections derived from allograft tumors of orally treated mice. Using this feature in conjunction with flow cytometry and confocal microscopy allowed to determine cellular drug accumulation levels, impact of the ABCB1 efflux pump and to uncover nintedanib trapping into lysosomes. Lysosomal sequestration - resulting in an organelle-specific and pH-dependent nintedanib fluorescence - was identified as an intrinsic resistance mechanism in FGFR-driven lung cancer cells. Accordingly, combination of nintedanib with agents compromising lysosomal acidification (bafilomycin A1, chloroquine) exerted distinctly synergistic growth inhibitory effects.\nCONCLUSION: Our findings provide a powerful tool to dissect molecular factors impacting organismal and intracellular pharmacokinetics of nintedanib. Regarding clinical application, prevention of lysosomal trapping via lysosome-alkalization might represent a promising strategy to circumvent cancer cell-intrinsic nintedanib resistance.", 
    "genre": "research_article", 
    "id": "sg:pub.10.1186/s13046-017-0592-3", 
    "inLanguage": [
      "en"
    ], 
    "isAccessibleForFree": true, 
    "isFundedItemOf": [
      {
        "id": "sg:grant.7579592", 
        "type": "MonetaryGrant"
      }
    ], 
    "isPartOf": [
      {
        "id": "sg:journal.1094159", 
        "issn": [
          "0392-9078", 
          "1756-9966"
        ], 
        "name": "Journal of Experimental & Clinical Cancer Research", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "1", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "36"
      }
    ], 
    "name": "Intrinsic fluorescence of the clinically approved multikinase inhibitor nintedanib reveals lysosomal sequestration as resistance mechanism in FGFR-driven lung cancer", 
    "pagination": "122", 
    "productId": [
      {
        "name": "readcube_id", 
        "type": "PropertyValue", 
        "value": [
          "b10bac499063a9ce034b515e1af01b31994e7f2a2841a73c74cf818037e9c210"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "28882160"
        ]
      }, 
      {
        "name": "nlm_unique_id", 
        "type": "PropertyValue", 
        "value": [
          "8308647"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1186/s13046-017-0592-3"
        ]
      }, 
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1091509957"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1186/s13046-017-0592-3", 
      "https://app.dimensions.ai/details/publication/pub.1091509957"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2019-04-10T19:56", 
    "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/v90/0000000001_0000000264/records_8681_00000509.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "http://link.springer.com/10.1186%2Fs13046-017-0592-3"
  }
]
 

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/s13046-017-0592-3'

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/s13046-017-0592-3'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1186/s13046-017-0592-3'

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

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1186/s13046-017-0592-3'


 

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

382 TRIPLES      21 PREDICATES      89 URIs      38 LITERALS      26 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1186/s13046-017-0592-3 schema:about N04328bf8770048d8a1f324d239f29303
2 N0e460cea2cc24d9383f733cbc0dc0081
3 N20cbfce0c44a448c823850794045f90e
4 N27685aa31e664eb6b5a9447ec9b38f64
5 N4229538117194102ad2c1912aff436fe
6 N4c741c1411ca4f5685947fbc74d75ff6
7 N63edb3cc2acd42da8657a969e854d3cf
8 N783b595124a4435f8b1a6feda189ac8c
9 N7c87a9eb861e48ea885312492042cb3f
10 N8c42121e240642a39fd6189b59cecc7e
11 N9261c498d5ea46899b3c5188e8c633c0
12 N9f30f9752d3d40aaa3bd679a8b189f88
13 Naa68ff34030e4d37980613b5e0d8ee9b
14 Ne502054aaee8401eb375a3d994563438
15 Necfe3d49bc4d4a2882acae5061199d35
16 Nfd9f99d058b64a239ae85b411564705f
17 Nfe5d287fe9c6420c8624416080216767
18 anzsrc-for:11
19 anzsrc-for:1112
20 schema:author Nebf939744f064e8991b03a8a83e9ca3a
21 schema:citation sg:pub.10.1007/978-3-540-69494-6_3
22 sg:pub.10.1007/s00249-008-0338-4
23 sg:pub.10.1038/35067100
24 sg:pub.10.1038/nchem.1961
25 sg:pub.10.1038/nrc2780
26 sg:pub.10.1038/sj.bjc.6605642
27 https://app.dimensions.ai/details/publication/pub.1077617215
28 https://doi.org/10.1002/jcph.752
29 https://doi.org/10.1002/med.21288
30 https://doi.org/10.1016/0006-2952(74)90174-9
31 https://doi.org/10.1016/0065-2571(84)90007-4
32 https://doi.org/10.1016/j.ctrv.2016.03.015
33 https://doi.org/10.1016/j.drup.2015.11.004
34 https://doi.org/10.1016/j.ejps.2017.04.016
35 https://doi.org/10.1016/j.freeradbiomed.2016.04.201
36 https://doi.org/10.1016/j.jchromb.2015.08.032
37 https://doi.org/10.1016/j.jchromb.2016.04.049
38 https://doi.org/10.1016/j.phrs.2016.12.021
39 https://doi.org/10.1016/j.semcdb.2015.10.012
40 https://doi.org/10.1016/j.semcdb.2015.12.014
41 https://doi.org/10.1016/j.tips.2016.10.003
42 https://doi.org/10.1016/j.tiv.2010.12.010
43 https://doi.org/10.1021/jm501562a
44 https://doi.org/10.1038/emboj.2012.32
45 https://doi.org/10.1039/c5cc06983a
46 https://doi.org/10.1124/mol.114.097451
47 https://doi.org/10.1152/ajpcell.00462.2010
48 https://doi.org/10.1158/0008-5472.can-11-3034
49 https://doi.org/10.1158/0008-5472.can-11-3654
50 https://doi.org/10.1158/1078-0432.ccr-13-3060
51 https://doi.org/10.1158/1078-0432.ccr-14-2329
52 https://doi.org/10.1158/1078-0432.ccr-14-3212
53 https://doi.org/10.1177/1753465815579608
54 https://doi.org/10.1177/1758834016630976
55 https://doi.org/10.1200/jco.2016.67.2048
56 https://doi.org/10.1517/13543776.2011.561784
57 https://doi.org/10.1517/14728222.2011.566217
58 https://doi.org/10.1529/biophysj.103.038422
59 https://doi.org/10.15586/jkcvhl.2015.44
60 https://doi.org/10.18632/oncotarget.10324
61 https://doi.org/10.18632/oncotarget.2732
62 https://doi.org/10.2174/1566524016666151222144231
63 https://doi.org/10.3892/ijmm.2016.2620
64 schema:datePublished 2017-12
65 schema:datePublishedReg 2017-12-01
66 schema:description BACKGROUND: Studying the intracellular distribution of pharmacological agents, including anticancer compounds, is of central importance in biomedical research. It constitutes a prerequisite for a better understanding of the molecular mechanisms underlying drug action and resistance development. Hyperactivated fibroblast growth factor receptors (FGFRs) constitute a promising therapy target in several types of malignancies including lung cancer. The clinically approved small-molecule FGFR inhibitor nintedanib exerts strong cytotoxicity in FGFR-driven lung cancer cells. However, subcellular pharmacokinetics of this compound and its impact on therapeutic efficacy remain obscure. METHODS: 3-dimensional fluorescence spectroscopy was conducted to asses cell-free nintedanib fluorescence properties. MTT assay was used to determine the impact of the lysosome-targeting agents bafilomycin A1 and chloroquine combined with nintedanib on lung cancer cell viability. Flow cytometry and live cell as well as confocal microscopy were performed to analyze uptake kinetics as well as subcellular distribution of nintedanib. Western blot was conducted to investigate protein expression. Cryosections of subcutaneous tumor allografts were generated to detect intratumoral nintedanib in mice after oral drug administration. RESULTS: Here, we report for the first time drug-intrinsic fluorescence properties of nintedanib in living and fixed cancer cells as well as in cryosections derived from allograft tumors of orally treated mice. Using this feature in conjunction with flow cytometry and confocal microscopy allowed to determine cellular drug accumulation levels, impact of the ABCB1 efflux pump and to uncover nintedanib trapping into lysosomes. Lysosomal sequestration - resulting in an organelle-specific and pH-dependent nintedanib fluorescence - was identified as an intrinsic resistance mechanism in FGFR-driven lung cancer cells. Accordingly, combination of nintedanib with agents compromising lysosomal acidification (bafilomycin A1, chloroquine) exerted distinctly synergistic growth inhibitory effects. CONCLUSION: Our findings provide a powerful tool to dissect molecular factors impacting organismal and intracellular pharmacokinetics of nintedanib. Regarding clinical application, prevention of lysosomal trapping via lysosome-alkalization might represent a promising strategy to circumvent cancer cell-intrinsic nintedanib resistance.
67 schema:genre research_article
68 schema:inLanguage en
69 schema:isAccessibleForFree true
70 schema:isPartOf Na765729d5258402291f4aba615939cb6
71 Nbba0f1a0472e4086965c50f86538eeb2
72 sg:journal.1094159
73 schema:name Intrinsic fluorescence of the clinically approved multikinase inhibitor nintedanib reveals lysosomal sequestration as resistance mechanism in FGFR-driven lung cancer
74 schema:pagination 122
75 schema:productId N041fe4b65ee541588c309de349f231dc
76 N28e1750676db479493d05b2b584e7348
77 N7fe99c451ee341f2aa1bc44d9ad9bca6
78 Nad0f961ee0914d2f82cb913fea0d1739
79 Nad7e0bfa9eb64195b2b331473d555a49
80 schema:sameAs https://app.dimensions.ai/details/publication/pub.1091509957
81 https://doi.org/10.1186/s13046-017-0592-3
82 schema:sdDatePublished 2019-04-10T19:56
83 schema:sdLicense https://scigraph.springernature.com/explorer/license/
84 schema:sdPublisher Nd8b6f75fce354bb6ae95f05493db4cb5
85 schema:url http://link.springer.com/10.1186%2Fs13046-017-0592-3
86 sgo:license sg:explorer/license/
87 sgo:sdDataset articles
88 rdf:type schema:ScholarlyArticle
89 N041fe4b65ee541588c309de349f231dc schema:name pubmed_id
90 schema:value 28882160
91 rdf:type schema:PropertyValue
92 N04328bf8770048d8a1f324d239f29303 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
93 schema:name Mice
94 rdf:type schema:DefinedTerm
95 N0d76ce4f733e47f19eb1d6d25b3bc372 rdf:first sg:person.0735503622.07
96 rdf:rest rdf:nil
97 N0e460cea2cc24d9383f733cbc0dc0081 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
98 schema:name Signal Transduction
99 rdf:type schema:DefinedTerm
100 N20cbfce0c44a448c823850794045f90e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
101 schema:name Phosphorylation
102 rdf:type schema:DefinedTerm
103 N27685aa31e664eb6b5a9447ec9b38f64 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
104 schema:name Fluorescence
105 rdf:type schema:DefinedTerm
106 N28e1750676db479493d05b2b584e7348 schema:name nlm_unique_id
107 schema:value 8308647
108 rdf:type schema:PropertyValue
109 N4229538117194102ad2c1912aff436fe schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
110 schema:name Cell Line, Tumor
111 rdf:type schema:DefinedTerm
112 N444f02e0cd14440f89f9c53832787df4 rdf:first sg:person.01174034333.95
113 rdf:rest N4a51902d7e24406e8faefa99a6ec87b6
114 N48db234279744ad6a52f986df4d393d8 rdf:first sg:person.0637641214.35
115 rdf:rest N96cc0a8c477b45699e2b8f4d34158493
116 N4a51902d7e24406e8faefa99a6ec87b6 rdf:first sg:person.0614165067.34
117 rdf:rest N5d0bbdc819c94abd96b100fcbf7fb790
118 N4c741c1411ca4f5685947fbc74d75ff6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
119 schema:name Xenograft Model Antitumor Assays
120 rdf:type schema:DefinedTerm
121 N4eaaefa586594ce6a9d326c4366d7d66 rdf:first sg:person.01214702556.78
122 rdf:rest N594b12a630204acd9da4c01b3f60cd10
123 N524bf069db2044d180ce37fbdddba9d4 rdf:first sg:person.01155541213.49
124 rdf:rest N4eaaefa586594ce6a9d326c4366d7d66
125 N594b12a630204acd9da4c01b3f60cd10 rdf:first sg:person.01223662745.79
126 rdf:rest N444f02e0cd14440f89f9c53832787df4
127 N5d0bbdc819c94abd96b100fcbf7fb790 rdf:first sg:person.016221256537.42
128 rdf:rest Nacc556ff301a44cead2ff7cc2896e64f
129 N63edb3cc2acd42da8657a969e854d3cf schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
130 schema:name Lung Neoplasms
131 rdf:type schema:DefinedTerm
132 N76374e7ac5d8467a8d75a7833efe6f4d rdf:first sg:person.015510741205.44
133 rdf:rest N524bf069db2044d180ce37fbdddba9d4
134 N783b595124a4435f8b1a6feda189ac8c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
135 schema:name Indoles
136 rdf:type schema:DefinedTerm
137 N7c87a9eb861e48ea885312492042cb3f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
138 schema:name Animals
139 rdf:type schema:DefinedTerm
140 N7d791f84c9d94ab8b0ba752597e5688c rdf:first sg:person.01124512740.04
141 rdf:rest N0d76ce4f733e47f19eb1d6d25b3bc372
142 N7fe99c451ee341f2aa1bc44d9ad9bca6 schema:name dimensions_id
143 schema:value pub.1091509957
144 rdf:type schema:PropertyValue
145 N8c42121e240642a39fd6189b59cecc7e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
146 schema:name Humans
147 rdf:type schema:DefinedTerm
148 N9261c498d5ea46899b3c5188e8c633c0 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
149 schema:name Lung
150 rdf:type schema:DefinedTerm
151 N94df65ab891047479b47976ed36687b2 rdf:first sg:person.01204222651.00
152 rdf:rest N7d791f84c9d94ab8b0ba752597e5688c
153 N96cc0a8c477b45699e2b8f4d34158493 rdf:first sg:person.01346501472.16
154 rdf:rest N94df65ab891047479b47976ed36687b2
155 N9f30f9752d3d40aaa3bd679a8b189f88 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
156 schema:name Macrolides
157 rdf:type schema:DefinedTerm
158 Na765729d5258402291f4aba615939cb6 schema:issueNumber 1
159 rdf:type schema:PublicationIssue
160 Naa68ff34030e4d37980613b5e0d8ee9b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
161 schema:name Cell Proliferation
162 rdf:type schema:DefinedTerm
163 Nacc556ff301a44cead2ff7cc2896e64f rdf:first sg:person.01225146250.81
164 rdf:rest Ncffe1866617d4c67a8210ff38da3cffd
165 Nad0f961ee0914d2f82cb913fea0d1739 schema:name doi
166 schema:value 10.1186/s13046-017-0592-3
167 rdf:type schema:PropertyValue
168 Nad7e0bfa9eb64195b2b331473d555a49 schema:name readcube_id
169 schema:value b10bac499063a9ce034b515e1af01b31994e7f2a2841a73c74cf818037e9c210
170 rdf:type schema:PropertyValue
171 Nbba0f1a0472e4086965c50f86538eeb2 schema:volumeNumber 36
172 rdf:type schema:PublicationVolume
173 Ncffe1866617d4c67a8210ff38da3cffd rdf:first sg:person.0674116056.53
174 rdf:rest N48db234279744ad6a52f986df4d393d8
175 Nd8b6f75fce354bb6ae95f05493db4cb5 schema:name Springer Nature - SN SciGraph project
176 rdf:type schema:Organization
177 Ne502054aaee8401eb375a3d994563438 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
178 schema:name Receptors, Fibroblast Growth Factor
179 rdf:type schema:DefinedTerm
180 Nebf939744f064e8991b03a8a83e9ca3a rdf:first sg:person.0754665152.41
181 rdf:rest N76374e7ac5d8467a8d75a7833efe6f4d
182 Necfe3d49bc4d4a2882acae5061199d35 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
183 schema:name Lysosomes
184 rdf:type schema:DefinedTerm
185 Nfd9f99d058b64a239ae85b411564705f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
186 schema:name Antineoplastic Combined Chemotherapy Protocols
187 rdf:type schema:DefinedTerm
188 Nfe5d287fe9c6420c8624416080216767 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
189 schema:name Drug Synergism
190 rdf:type schema:DefinedTerm
191 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
192 schema:name Medical and Health Sciences
193 rdf:type schema:DefinedTerm
194 anzsrc-for:1112 schema:inDefinedTermSet anzsrc-for:
195 schema:name Oncology and Carcinogenesis
196 rdf:type schema:DefinedTerm
197 sg:grant.7579592 http://pending.schema.org/fundedItem sg:pub.10.1186/s13046-017-0592-3
198 rdf:type schema:MonetaryGrant
199 sg:journal.1094159 schema:issn 0392-9078
200 1756-9966
201 schema:name Journal of Experimental & Clinical Cancer Research
202 rdf:type schema:Periodical
203 sg:person.01124512740.04 schema:affiliation https://www.grid.ac/institutes/grid.22937.3d
204 schema:familyName Grusch
205 schema:givenName Michael
206 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01124512740.04
207 rdf:type schema:Person
208 sg:person.01155541213.49 schema:affiliation https://www.grid.ac/institutes/grid.466769.c
209 schema:familyName Senkiv
210 schema:givenName Julia
211 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01155541213.49
212 rdf:type schema:Person
213 sg:person.01174034333.95 schema:affiliation https://www.grid.ac/institutes/grid.22937.3d
214 schema:familyName van Schoonhoven
215 schema:givenName Sushilla
216 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01174034333.95
217 rdf:type schema:Person
218 sg:person.01204222651.00 schema:affiliation https://www.grid.ac/institutes/grid.10420.37
219 schema:familyName Heffeter
220 schema:givenName Petra
221 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01204222651.00
222 rdf:type schema:Person
223 sg:person.01214702556.78 schema:affiliation https://www.grid.ac/institutes/grid.10420.37
224 schema:familyName Heilos
225 schema:givenName Daniela
226 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01214702556.78
227 rdf:type schema:Person
228 sg:person.01223662745.79 schema:affiliation https://www.grid.ac/institutes/grid.22937.3d
229 schema:familyName Gabler
230 schema:givenName Lisa
231 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01223662745.79
232 rdf:type schema:Person
233 sg:person.01225146250.81 schema:affiliation https://www.grid.ac/institutes/grid.22937.3d
234 schema:familyName Pirker
235 schema:givenName Christine
236 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01225146250.81
237 rdf:type schema:Person
238 sg:person.01346501472.16 schema:affiliation https://www.grid.ac/institutes/grid.10420.37
239 schema:familyName Kowol
240 schema:givenName Christian R.
241 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01346501472.16
242 rdf:type schema:Person
243 sg:person.015510741205.44 schema:affiliation https://www.grid.ac/institutes/grid.10420.37
244 schema:familyName Kallus
245 schema:givenName Sebastian
246 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.015510741205.44
247 rdf:type schema:Person
248 sg:person.016221256537.42 schema:affiliation https://www.grid.ac/institutes/grid.22937.3d
249 schema:familyName Moser
250 schema:givenName Patrick
251 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016221256537.42
252 rdf:type schema:Person
253 sg:person.0614165067.34 schema:affiliation https://www.grid.ac/institutes/grid.10420.37
254 schema:familyName Terenzi
255 schema:givenName Alessio
256 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0614165067.34
257 rdf:type schema:Person
258 sg:person.0637641214.35 schema:affiliation https://www.grid.ac/institutes/grid.10420.37
259 schema:familyName Jäger
260 schema:givenName Walter
261 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0637641214.35
262 rdf:type schema:Person
263 sg:person.0674116056.53 schema:affiliation https://www.grid.ac/institutes/grid.22937.3d
264 schema:familyName Timelthaler
265 schema:givenName Gerald
266 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0674116056.53
267 rdf:type schema:Person
268 sg:person.0735503622.07 schema:affiliation https://www.grid.ac/institutes/grid.10420.37
269 schema:familyName Berger
270 schema:givenName Walter
271 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0735503622.07
272 rdf:type schema:Person
273 sg:person.0754665152.41 schema:affiliation https://www.grid.ac/institutes/grid.22937.3d
274 schema:familyName Englinger
275 schema:givenName Bernhard
276 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0754665152.41
277 rdf:type schema:Person
278 sg:pub.10.1007/978-3-540-69494-6_3 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018827762
279 https://doi.org/10.1007/978-3-540-69494-6_3
280 rdf:type schema:CreativeWork
281 sg:pub.10.1007/s00249-008-0338-4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045739897
282 https://doi.org/10.1007/s00249-008-0338-4
283 rdf:type schema:CreativeWork
284 sg:pub.10.1038/35067100 schema:sameAs https://app.dimensions.ai/details/publication/pub.1029980557
285 https://doi.org/10.1038/35067100
286 rdf:type schema:CreativeWork
287 sg:pub.10.1038/nchem.1961 schema:sameAs https://app.dimensions.ai/details/publication/pub.1032194266
288 https://doi.org/10.1038/nchem.1961
289 rdf:type schema:CreativeWork
290 sg:pub.10.1038/nrc2780 schema:sameAs https://app.dimensions.ai/details/publication/pub.1025760788
291 https://doi.org/10.1038/nrc2780
292 rdf:type schema:CreativeWork
293 sg:pub.10.1038/sj.bjc.6605642 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034513961
294 https://doi.org/10.1038/sj.bjc.6605642
295 rdf:type schema:CreativeWork
296 https://app.dimensions.ai/details/publication/pub.1077617215 schema:CreativeWork
297 https://doi.org/10.1002/jcph.752 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031999675
298 rdf:type schema:CreativeWork
299 https://doi.org/10.1002/med.21288 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010892806
300 rdf:type schema:CreativeWork
301 https://doi.org/10.1016/0006-2952(74)90174-9 schema:sameAs https://app.dimensions.ai/details/publication/pub.1025224101
302 rdf:type schema:CreativeWork
303 https://doi.org/10.1016/0065-2571(84)90007-4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026371633
304 rdf:type schema:CreativeWork
305 https://doi.org/10.1016/j.ctrv.2016.03.015 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022926671
306 rdf:type schema:CreativeWork
307 https://doi.org/10.1016/j.drup.2015.11.004 schema:sameAs https://app.dimensions.ai/details/publication/pub.1027719327
308 rdf:type schema:CreativeWork
309 https://doi.org/10.1016/j.ejps.2017.04.016 schema:sameAs https://app.dimensions.ai/details/publication/pub.1085119367
310 rdf:type schema:CreativeWork
311 https://doi.org/10.1016/j.freeradbiomed.2016.04.201 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014404203
312 rdf:type schema:CreativeWork
313 https://doi.org/10.1016/j.jchromb.2015.08.032 schema:sameAs https://app.dimensions.ai/details/publication/pub.1001719307
314 rdf:type schema:CreativeWork
315 https://doi.org/10.1016/j.jchromb.2016.04.049 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004636224
316 rdf:type schema:CreativeWork
317 https://doi.org/10.1016/j.phrs.2016.12.021 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003591175
318 rdf:type schema:CreativeWork
319 https://doi.org/10.1016/j.semcdb.2015.10.012 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033061162
320 rdf:type schema:CreativeWork
321 https://doi.org/10.1016/j.semcdb.2015.12.014 schema:sameAs https://app.dimensions.ai/details/publication/pub.1047294719
322 rdf:type schema:CreativeWork
323 https://doi.org/10.1016/j.tips.2016.10.003 schema:sameAs https://app.dimensions.ai/details/publication/pub.1035581892
324 rdf:type schema:CreativeWork
325 https://doi.org/10.1016/j.tiv.2010.12.010 schema:sameAs https://app.dimensions.ai/details/publication/pub.1019945857
326 rdf:type schema:CreativeWork
327 https://doi.org/10.1021/jm501562a schema:sameAs https://app.dimensions.ai/details/publication/pub.1018667497
328 rdf:type schema:CreativeWork
329 https://doi.org/10.1038/emboj.2012.32 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018656852
330 rdf:type schema:CreativeWork
331 https://doi.org/10.1039/c5cc06983a schema:sameAs https://app.dimensions.ai/details/publication/pub.1015184058
332 rdf:type schema:CreativeWork
333 https://doi.org/10.1124/mol.114.097451 schema:sameAs https://app.dimensions.ai/details/publication/pub.1043604822
334 rdf:type schema:CreativeWork
335 https://doi.org/10.1152/ajpcell.00462.2010 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005635627
336 rdf:type schema:CreativeWork
337 https://doi.org/10.1158/0008-5472.can-11-3034 schema:sameAs https://app.dimensions.ai/details/publication/pub.1047723989
338 rdf:type schema:CreativeWork
339 https://doi.org/10.1158/0008-5472.can-11-3654 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046115607
340 rdf:type schema:CreativeWork
341 https://doi.org/10.1158/1078-0432.ccr-13-3060 schema:sameAs https://app.dimensions.ai/details/publication/pub.1009839645
342 rdf:type schema:CreativeWork
343 https://doi.org/10.1158/1078-0432.ccr-14-2329 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028097305
344 rdf:type schema:CreativeWork
345 https://doi.org/10.1158/1078-0432.ccr-14-3212 schema:sameAs https://app.dimensions.ai/details/publication/pub.1063224838
346 rdf:type schema:CreativeWork
347 https://doi.org/10.1177/1753465815579608 schema:sameAs https://app.dimensions.ai/details/publication/pub.1048200583
348 rdf:type schema:CreativeWork
349 https://doi.org/10.1177/1758834016630976 schema:sameAs https://app.dimensions.ai/details/publication/pub.1064077375
350 rdf:type schema:CreativeWork
351 https://doi.org/10.1200/jco.2016.67.2048 schema:sameAs https://app.dimensions.ai/details/publication/pub.1036774524
352 rdf:type schema:CreativeWork
353 https://doi.org/10.1517/13543776.2011.561784 schema:sameAs https://app.dimensions.ai/details/publication/pub.1017358753
354 rdf:type schema:CreativeWork
355 https://doi.org/10.1517/14728222.2011.566217 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014607436
356 rdf:type schema:CreativeWork
357 https://doi.org/10.1529/biophysj.103.038422 schema:sameAs https://app.dimensions.ai/details/publication/pub.1017631680
358 rdf:type schema:CreativeWork
359 https://doi.org/10.15586/jkcvhl.2015.44 schema:sameAs https://app.dimensions.ai/details/publication/pub.1067984661
360 rdf:type schema:CreativeWork
361 https://doi.org/10.18632/oncotarget.10324 schema:sameAs https://app.dimensions.ai/details/publication/pub.1049478933
362 rdf:type schema:CreativeWork
363 https://doi.org/10.18632/oncotarget.2732 schema:sameAs https://app.dimensions.ai/details/publication/pub.1011489635
364 rdf:type schema:CreativeWork
365 https://doi.org/10.2174/1566524016666151222144231 schema:sameAs https://app.dimensions.ai/details/publication/pub.1069185368
366 rdf:type schema:CreativeWork
367 https://doi.org/10.3892/ijmm.2016.2620 schema:sameAs https://app.dimensions.ai/details/publication/pub.1071508496
368 rdf:type schema:CreativeWork
369 https://www.grid.ac/institutes/grid.10420.37 schema:alternateName University of Vienna
370 schema:name Department of Pharmaceutical Chemistry, Division of Clinical Pharmacy and Diagnostics, University of Vienna, Althanstrasse 14, A-1090, Vienna, Austria
371 Department of Pharmacology and Toxicology, University of Vienna, Althanstr. 14, 1090, Vienna, Austria
372 Institute of Cancer Research and Comprehensive Cancer Center, Department of Medicine I, Medical University of Vienna, Borschkegasse 8a, A-1090, Vienna, Austria
373 Institute of Inorganic Chemistry, University of Vienna, Waehringer Str. 42, A-1090, Vienna, Austria
374 Research Cluster “Translational Cancer Therapy Research”, University of Vienna, Waehringer Strasse 42, A-1090, Vienna, Austria
375 rdf:type schema:Organization
376 https://www.grid.ac/institutes/grid.22937.3d schema:alternateName Medical University of Vienna
377 schema:name Institute of Cancer Research and Comprehensive Cancer Center, Department of Medicine I, Medical University of Vienna, Borschkegasse 8a, A-1090, Vienna, Austria
378 rdf:type schema:Organization
379 https://www.grid.ac/institutes/grid.466769.c schema:alternateName Institute of Cell Biology
380 schema:name Institute of Cancer Research and Comprehensive Cancer Center, Department of Medicine I, Medical University of Vienna, Borschkegasse 8a, A-1090, Vienna, Austria
381 Institute of Cell Biology NAS of Ukraine, Drahomanova str 14/16, 79005, Lviv, Ukraine
382 rdf:type schema:Organization
 




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


...