Tumor-treating fields elicit a conditional vulnerability to ionizing radiation via the downregulation of BRCA1 signaling and reduced DNA double-strand break ... View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-03

AUTHORS

Narasimha Kumar Karanam, Kalayarasan Srinivasan, Lianghao Ding, Brock Sishc, Debabrata Saha, Michael D Story

ABSTRACT

The use of tumor-treating fields (TTFields) has revolutionized the treatment of recurrent and newly diagnosed glioblastoma (GBM). TTFields are low-intensity, intermediate frequency, alternating electric fields that are applied to tumor regions and cells using non-invasive arrays. The predominant mechanism by which TTFields are thought to kill tumor cells is the disruption of mitosis. Using five non-small cell lung cancer (NSCLC) cell lines we found that there is a variable response in cell proliferation and cell killing between these NSCLC cell lines that was independent of p53 status. TTFields treatment increased the G2/M population, with a concomitant reduction in S-phase cells followed by the appearance of a sub-G1 population indicative of apoptosis. Temporal changes in gene expression during TTFields exposure was evaluated to identify molecular signaling changes underlying the differential TTFields response. The most differentially expressed genes were associated with the cell cycle and cell proliferation pathways. However, the expression of genes found within the BRCA1 DNA-damage response were significantly downregulated (P<0.05) during TTFields treatment. DNA double-strand break (DSB) repair foci increased when cells were exposed to TTFields as did the appearance of chromatid-type aberrations, suggesting an interphase mechanism responsible for cell death involving DNA repair. Exposing cells to TTFields immediately following ionizing radiation resulted in increased chromatid aberrations and a reduced capacity to repair DNA DSBs, which were likely responsible for at least a portion of the enhanced cell killing seen with the combination. These findings suggest that TTFields induce a state of 'BRCAness' leading to a conditional susceptibility resulting in enhanced sensitivity to ionizing radiation and provides a strong rationale for the use of TTFields as a combined modality therapy with radiation or other DNA-damaging agents. More... »

PAGES

e2711

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/cddis.2017.136

DOI

http://dx.doi.org/10.1038/cddis.2017.136

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1084127854

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28358361


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": "A549 Cells", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "BRCA1 Protein", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Carcinoma, Non-Small-Cell Lung", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "DNA Breaks, Double-Stranded", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "DNA Repair", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Down-Regulation", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Gamma Rays", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Gene Expression Regulation, Neoplastic", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Humans", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Lung Neoplasms", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Signal Transduction", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "The University of Texas Southwestern Medical Center", 
          "id": "https://www.grid.ac/institutes/grid.267313.2", 
          "name": [
            "Division of Molecular Radiation Biology, Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Karanam", 
        "givenName": "Narasimha Kumar", 
        "id": "sg:person.01242441073.25", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01242441073.25"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "The University of Texas Southwestern Medical Center", 
          "id": "https://www.grid.ac/institutes/grid.267313.2", 
          "name": [
            "Division of Molecular Radiation Biology, Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Srinivasan", 
        "givenName": "Kalayarasan", 
        "id": "sg:person.01026760347.01", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01026760347.01"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "The University of Texas Southwestern Medical Center", 
          "id": "https://www.grid.ac/institutes/grid.267313.2", 
          "name": [
            "Division of Molecular Radiation Biology, Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Ding", 
        "givenName": "Lianghao", 
        "id": "sg:person.016167177547.40", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016167177547.40"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "The University of Texas Southwestern Medical Center", 
          "id": "https://www.grid.ac/institutes/grid.267313.2", 
          "name": [
            "Division of Molecular Radiation Biology, Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Sishc", 
        "givenName": "Brock", 
        "id": "sg:person.01272142221.76", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01272142221.76"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "The University of Texas Southwestern Medical Center", 
          "id": "https://www.grid.ac/institutes/grid.267313.2", 
          "name": [
            "Division of Molecular Radiation Biology, Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Saha", 
        "givenName": "Debabrata", 
        "id": "sg:person.010066141677.08", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010066141677.08"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "The University of Texas Southwestern Medical Center", 
          "id": "https://www.grid.ac/institutes/grid.267313.2", 
          "name": [
            "Division of Molecular Radiation Biology, Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA", 
            "Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Story", 
        "givenName": "Michael D", 
        "id": "sg:person.01073537512.86", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01073537512.86"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "https://doi.org/10.1016/j.pan.2013.11.009", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1000383508"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature03114", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1000698068", 
          "https://doi.org/10.1038/nature03114"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature03114", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1000698068", 
          "https://doi.org/10.1038/nature03114"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1083/jcb.151.7.1381", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1002675122"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s10585-009-9262-y", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1002765672", 
          "https://doi.org/10.1007/s10585-009-9262-y"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s10585-009-9262-y", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1002765672", 
          "https://doi.org/10.1007/s10585-009-9262-y"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s10585-009-9262-y", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1002765672", 
          "https://doi.org/10.1007/s10585-009-9262-y"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1038/msb4100116", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1006097382"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1038/msb4100116", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1006097382"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1111/nyas.12112", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1007050840"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/0008-5472.can-04-0083", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1010702956"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/cam4.210", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1012332812"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1152/ajpendo.00308.2012", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1012620834"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/01.jto.0000391367.63882.79", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1013764548"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.3322/caac.21220", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1014250067"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1101/gad.2053211", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1014251409"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/jto.0b013e3181ec809b", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1014594271"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1053/j.seminoncol.2014.09.009", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1015713508"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/s13053-015-0038-x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1015885733", 
          "https://doi.org/10.1186/s13053-015-0038-x"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/s13053-015-0038-x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1015885733", 
          "https://doi.org/10.1186/s13053-015-0038-x"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.chroma.2005.03.070", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1016380180"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nrc3181", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1016615579", 
          "https://doi.org/10.1038/nrc3181"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/prp2.149", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1018270796"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/0008-5472.can-07-0369", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1019813566"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.ijrobp.2015.05.037", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1021153459"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1001/jama.2015.16669", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1024093685"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/ijc.30406", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1024554742"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1200/jco.2013.53.1228", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1026492122"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/nar/gkn234", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1027599014"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.18632/oncotarget.11407", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1029447102"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/1471-2407-10-229", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1030456365", 
          "https://doi.org/10.1186/1471-2407-10-229"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1074/jbc.m500963200", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1033465522"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.18632/oncotarget.6659", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1035778473"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/hmg/ddl002", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1037307111"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ncb1882", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1037394989", 
          "https://doi.org/10.1038/ncb1882"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1073/pnas.0702916104", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1039241372"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1053/j.seminoncol.2014.09.006", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1040012676"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nrc1457", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1042257134", 
          "https://doi.org/10.1038/nrc1457"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nrc1457", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1042257134", 
          "https://doi.org/10.1038/nrc1457"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1038/emboj.2010.238", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1043596363"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/srep18046", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1044985306", 
          "https://doi.org/10.1038/srep18046"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s1097-2765(00)80035-0", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1045196719"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.3389/fonc.2015.00257", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1049126725"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1200/jco.2014.55.1929", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1050249529"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/1756-6649-9-1", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1051028910", 
          "https://doi.org/10.1186/1756-6649-9-1"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/1756-6649-9-1", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1051028910", 
          "https://doi.org/10.1186/1756-6649-9-1"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/0008-5472.can-06-2627", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1051995727"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nrc1691", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1052792626", 
          "https://doi.org/10.1038/nrc1691"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nrc1691", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1052792626", 
          "https://doi.org/10.1038/nrc1691"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1371/journal.pone.0125269", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1053720068"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1079293467", 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2017-03", 
    "datePublishedReg": "2017-03-01", 
    "description": "The use of tumor-treating fields (TTFields) has revolutionized the treatment of recurrent and newly diagnosed glioblastoma (GBM). TTFields are low-intensity, intermediate frequency, alternating electric fields that are applied to tumor regions and cells using non-invasive arrays. The predominant mechanism by which TTFields are thought to kill tumor cells is the disruption of mitosis. Using five non-small cell lung cancer (NSCLC) cell lines we found that there is a variable response in cell proliferation and cell killing between these NSCLC cell lines that was independent of p53 status. TTFields treatment increased the G2/M population, with a concomitant reduction in S-phase cells followed by the appearance of a sub-G1 population indicative of apoptosis. Temporal changes in gene expression during TTFields exposure was evaluated to identify molecular signaling changes underlying the differential TTFields response. The most differentially expressed genes were associated with the cell cycle and cell proliferation pathways. However, the expression of genes found within the BRCA1 DNA-damage response were significantly downregulated (P<0.05) during TTFields treatment. DNA double-strand break (DSB) repair foci increased when cells were exposed to TTFields as did the appearance of chromatid-type aberrations, suggesting an interphase mechanism responsible for cell death involving DNA repair. Exposing cells to TTFields immediately following ionizing radiation resulted in increased chromatid aberrations and a reduced capacity to repair DNA DSBs, which were likely responsible for at least a portion of the enhanced cell killing seen with the combination. These findings suggest that TTFields induce a state of 'BRCAness' leading to a conditional susceptibility resulting in enhanced sensitivity to ionizing radiation and provides a strong rationale for the use of TTFields as a combined modality therapy with radiation or other DNA-damaging agents.", 
    "genre": "research_article", 
    "id": "sg:pub.10.1038/cddis.2017.136", 
    "inLanguage": [
      "en"
    ], 
    "isAccessibleForFree": true, 
    "isPartOf": [
      {
        "id": "sg:journal.1042939", 
        "issn": [
          "2041-4889"
        ], 
        "name": "Cell Death & Disease", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "3", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "8"
      }
    ], 
    "name": "Tumor-treating fields elicit a conditional vulnerability to ionizing radiation via the downregulation of BRCA1 signaling and reduced DNA double-strand break repair capacity in non-small cell lung cancer cell lines", 
    "pagination": "e2711", 
    "productId": [
      {
        "name": "readcube_id", 
        "type": "PropertyValue", 
        "value": [
          "13e5004652dae89d9da3fcd886ffd1491950d121203fe6abe475f742d85de2f0"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "28358361"
        ]
      }, 
      {
        "name": "nlm_unique_id", 
        "type": "PropertyValue", 
        "value": [
          "101524092"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1038/cddis.2017.136"
        ]
      }, 
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1084127854"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1038/cddis.2017.136", 
      "https://app.dimensions.ai/details/publication/pub.1084127854"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2019-04-10T13:00", 
    "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_8659_00000434.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://www.nature.com/articles/cddis2017136"
  }
]
 

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/cddis.2017.136'

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/cddis.2017.136'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/cddis.2017.136'

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

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/cddis.2017.136'


 

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

286 TRIPLES      21 PREDICATES      83 URIs      32 LITERALS      20 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1038/cddis.2017.136 schema:about N1baee9d7feea41ba86316f063139b1e8
2 N1fbc92252c8b4bbf8b83c4cc524f51ec
3 N3f578d83eca5497a9ee63f2a74678ca8
4 N71cae419c96c4d1c90ee44b487f03417
5 N76515223bac64ad5a31f42f90e719ac3
6 N88371a8e994d41daa2bc04fa70718cba
7 N91e39509fbed4cf29987d2d7da97cde5
8 N95df23b2373548c5993cab5066579882
9 Naf2ceb43409c43749ab321048dc93430
10 Nce932ef993fd48feabcca4cde1b7d84c
11 Nd3cb581ab18548d8bb25f06c62874a28
12 anzsrc-for:11
13 anzsrc-for:1112
14 schema:author N649fb10400d9451eb01a877ab046ff78
15 schema:citation sg:pub.10.1007/s10585-009-9262-y
16 sg:pub.10.1038/nature03114
17 sg:pub.10.1038/ncb1882
18 sg:pub.10.1038/nrc1457
19 sg:pub.10.1038/nrc1691
20 sg:pub.10.1038/nrc3181
21 sg:pub.10.1038/srep18046
22 sg:pub.10.1186/1471-2407-10-229
23 sg:pub.10.1186/1756-6649-9-1
24 sg:pub.10.1186/s13053-015-0038-x
25 https://app.dimensions.ai/details/publication/pub.1079293467
26 https://doi.org/10.1001/jama.2015.16669
27 https://doi.org/10.1002/cam4.210
28 https://doi.org/10.1002/ijc.30406
29 https://doi.org/10.1002/prp2.149
30 https://doi.org/10.1016/j.chroma.2005.03.070
31 https://doi.org/10.1016/j.ijrobp.2015.05.037
32 https://doi.org/10.1016/j.pan.2013.11.009
33 https://doi.org/10.1016/s1097-2765(00)80035-0
34 https://doi.org/10.1038/emboj.2010.238
35 https://doi.org/10.1038/msb4100116
36 https://doi.org/10.1053/j.seminoncol.2014.09.006
37 https://doi.org/10.1053/j.seminoncol.2014.09.009
38 https://doi.org/10.1073/pnas.0702916104
39 https://doi.org/10.1074/jbc.m500963200
40 https://doi.org/10.1083/jcb.151.7.1381
41 https://doi.org/10.1093/hmg/ddl002
42 https://doi.org/10.1093/nar/gkn234
43 https://doi.org/10.1097/01.jto.0000391367.63882.79
44 https://doi.org/10.1097/jto.0b013e3181ec809b
45 https://doi.org/10.1101/gad.2053211
46 https://doi.org/10.1111/nyas.12112
47 https://doi.org/10.1152/ajpendo.00308.2012
48 https://doi.org/10.1158/0008-5472.can-04-0083
49 https://doi.org/10.1158/0008-5472.can-06-2627
50 https://doi.org/10.1158/0008-5472.can-07-0369
51 https://doi.org/10.1200/jco.2013.53.1228
52 https://doi.org/10.1200/jco.2014.55.1929
53 https://doi.org/10.1371/journal.pone.0125269
54 https://doi.org/10.18632/oncotarget.11407
55 https://doi.org/10.18632/oncotarget.6659
56 https://doi.org/10.3322/caac.21220
57 https://doi.org/10.3389/fonc.2015.00257
58 schema:datePublished 2017-03
59 schema:datePublishedReg 2017-03-01
60 schema:description The use of tumor-treating fields (TTFields) has revolutionized the treatment of recurrent and newly diagnosed glioblastoma (GBM). TTFields are low-intensity, intermediate frequency, alternating electric fields that are applied to tumor regions and cells using non-invasive arrays. The predominant mechanism by which TTFields are thought to kill tumor cells is the disruption of mitosis. Using five non-small cell lung cancer (NSCLC) cell lines we found that there is a variable response in cell proliferation and cell killing between these NSCLC cell lines that was independent of p53 status. TTFields treatment increased the G2/M population, with a concomitant reduction in S-phase cells followed by the appearance of a sub-G1 population indicative of apoptosis. Temporal changes in gene expression during TTFields exposure was evaluated to identify molecular signaling changes underlying the differential TTFields response. The most differentially expressed genes were associated with the cell cycle and cell proliferation pathways. However, the expression of genes found within the BRCA1 DNA-damage response were significantly downregulated (P<0.05) during TTFields treatment. DNA double-strand break (DSB) repair foci increased when cells were exposed to TTFields as did the appearance of chromatid-type aberrations, suggesting an interphase mechanism responsible for cell death involving DNA repair. Exposing cells to TTFields immediately following ionizing radiation resulted in increased chromatid aberrations and a reduced capacity to repair DNA DSBs, which were likely responsible for at least a portion of the enhanced cell killing seen with the combination. These findings suggest that TTFields induce a state of 'BRCAness' leading to a conditional susceptibility resulting in enhanced sensitivity to ionizing radiation and provides a strong rationale for the use of TTFields as a combined modality therapy with radiation or other DNA-damaging agents.
61 schema:genre research_article
62 schema:inLanguage en
63 schema:isAccessibleForFree true
64 schema:isPartOf Na4bc7577e3944e0b9706e1030c283ac9
65 Ne126bb13bd054bda8a439c30a915a5da
66 sg:journal.1042939
67 schema:name Tumor-treating fields elicit a conditional vulnerability to ionizing radiation via the downregulation of BRCA1 signaling and reduced DNA double-strand break repair capacity in non-small cell lung cancer cell lines
68 schema:pagination e2711
69 schema:productId N066615ffd6374beaae03f0032a45ec56
70 N1b7767c3e2504d558e34c8e0119d6485
71 N2def512cf6e94537953ea757466ed0b0
72 N83a4ed43f00e49cf82d1bdaacadffe23
73 N8c5a3d9a269a446c9d5a37b6e96c67a9
74 schema:sameAs https://app.dimensions.ai/details/publication/pub.1084127854
75 https://doi.org/10.1038/cddis.2017.136
76 schema:sdDatePublished 2019-04-10T13:00
77 schema:sdLicense https://scigraph.springernature.com/explorer/license/
78 schema:sdPublisher N0fd7840b173f4468a7770ddfd7d14392
79 schema:url https://www.nature.com/articles/cddis2017136
80 sgo:license sg:explorer/license/
81 sgo:sdDataset articles
82 rdf:type schema:ScholarlyArticle
83 N066615ffd6374beaae03f0032a45ec56 schema:name dimensions_id
84 schema:value pub.1084127854
85 rdf:type schema:PropertyValue
86 N0fd7840b173f4468a7770ddfd7d14392 schema:name Springer Nature - SN SciGraph project
87 rdf:type schema:Organization
88 N147bc25ed04b4f2d9b053504f1e36aa1 rdf:first sg:person.01026760347.01
89 rdf:rest Nc132e588e8ed4316ae281b55390095e5
90 N1b7767c3e2504d558e34c8e0119d6485 schema:name readcube_id
91 schema:value 13e5004652dae89d9da3fcd886ffd1491950d121203fe6abe475f742d85de2f0
92 rdf:type schema:PropertyValue
93 N1baee9d7feea41ba86316f063139b1e8 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
94 schema:name DNA Repair
95 rdf:type schema:DefinedTerm
96 N1fbc92252c8b4bbf8b83c4cc524f51ec schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
97 schema:name Gamma Rays
98 rdf:type schema:DefinedTerm
99 N2c677f4128e240acaac7d3e5ae689fe5 rdf:first sg:person.01272142221.76
100 rdf:rest Ne6f5f62274664617ae22455a989f0c35
101 N2def512cf6e94537953ea757466ed0b0 schema:name doi
102 schema:value 10.1038/cddis.2017.136
103 rdf:type schema:PropertyValue
104 N3f578d83eca5497a9ee63f2a74678ca8 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
105 schema:name Lung Neoplasms
106 rdf:type schema:DefinedTerm
107 N649fb10400d9451eb01a877ab046ff78 rdf:first sg:person.01242441073.25
108 rdf:rest N147bc25ed04b4f2d9b053504f1e36aa1
109 N71cae419c96c4d1c90ee44b487f03417 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
110 schema:name Carcinoma, Non-Small-Cell Lung
111 rdf:type schema:DefinedTerm
112 N76515223bac64ad5a31f42f90e719ac3 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
113 schema:name DNA Breaks, Double-Stranded
114 rdf:type schema:DefinedTerm
115 N83a4ed43f00e49cf82d1bdaacadffe23 schema:name pubmed_id
116 schema:value 28358361
117 rdf:type schema:PropertyValue
118 N88371a8e994d41daa2bc04fa70718cba schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
119 schema:name Down-Regulation
120 rdf:type schema:DefinedTerm
121 N8b26f98d0d5d4306a924e8aab15860f0 rdf:first sg:person.01073537512.86
122 rdf:rest rdf:nil
123 N8c5a3d9a269a446c9d5a37b6e96c67a9 schema:name nlm_unique_id
124 schema:value 101524092
125 rdf:type schema:PropertyValue
126 N91e39509fbed4cf29987d2d7da97cde5 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
127 schema:name A549 Cells
128 rdf:type schema:DefinedTerm
129 N95df23b2373548c5993cab5066579882 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
130 schema:name Signal Transduction
131 rdf:type schema:DefinedTerm
132 Na4bc7577e3944e0b9706e1030c283ac9 schema:issueNumber 3
133 rdf:type schema:PublicationIssue
134 Naf2ceb43409c43749ab321048dc93430 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
135 schema:name Gene Expression Regulation, Neoplastic
136 rdf:type schema:DefinedTerm
137 Nc132e588e8ed4316ae281b55390095e5 rdf:first sg:person.016167177547.40
138 rdf:rest N2c677f4128e240acaac7d3e5ae689fe5
139 Nce932ef993fd48feabcca4cde1b7d84c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
140 schema:name Humans
141 rdf:type schema:DefinedTerm
142 Nd3cb581ab18548d8bb25f06c62874a28 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
143 schema:name BRCA1 Protein
144 rdf:type schema:DefinedTerm
145 Ne126bb13bd054bda8a439c30a915a5da schema:volumeNumber 8
146 rdf:type schema:PublicationVolume
147 Ne6f5f62274664617ae22455a989f0c35 rdf:first sg:person.010066141677.08
148 rdf:rest N8b26f98d0d5d4306a924e8aab15860f0
149 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
150 schema:name Medical and Health Sciences
151 rdf:type schema:DefinedTerm
152 anzsrc-for:1112 schema:inDefinedTermSet anzsrc-for:
153 schema:name Oncology and Carcinogenesis
154 rdf:type schema:DefinedTerm
155 sg:journal.1042939 schema:issn 2041-4889
156 schema:name Cell Death & Disease
157 rdf:type schema:Periodical
158 sg:person.010066141677.08 schema:affiliation https://www.grid.ac/institutes/grid.267313.2
159 schema:familyName Saha
160 schema:givenName Debabrata
161 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010066141677.08
162 rdf:type schema:Person
163 sg:person.01026760347.01 schema:affiliation https://www.grid.ac/institutes/grid.267313.2
164 schema:familyName Srinivasan
165 schema:givenName Kalayarasan
166 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01026760347.01
167 rdf:type schema:Person
168 sg:person.01073537512.86 schema:affiliation https://www.grid.ac/institutes/grid.267313.2
169 schema:familyName Story
170 schema:givenName Michael D
171 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01073537512.86
172 rdf:type schema:Person
173 sg:person.01242441073.25 schema:affiliation https://www.grid.ac/institutes/grid.267313.2
174 schema:familyName Karanam
175 schema:givenName Narasimha Kumar
176 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01242441073.25
177 rdf:type schema:Person
178 sg:person.01272142221.76 schema:affiliation https://www.grid.ac/institutes/grid.267313.2
179 schema:familyName Sishc
180 schema:givenName Brock
181 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01272142221.76
182 rdf:type schema:Person
183 sg:person.016167177547.40 schema:affiliation https://www.grid.ac/institutes/grid.267313.2
184 schema:familyName Ding
185 schema:givenName Lianghao
186 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016167177547.40
187 rdf:type schema:Person
188 sg:pub.10.1007/s10585-009-9262-y schema:sameAs https://app.dimensions.ai/details/publication/pub.1002765672
189 https://doi.org/10.1007/s10585-009-9262-y
190 rdf:type schema:CreativeWork
191 sg:pub.10.1038/nature03114 schema:sameAs https://app.dimensions.ai/details/publication/pub.1000698068
192 https://doi.org/10.1038/nature03114
193 rdf:type schema:CreativeWork
194 sg:pub.10.1038/ncb1882 schema:sameAs https://app.dimensions.ai/details/publication/pub.1037394989
195 https://doi.org/10.1038/ncb1882
196 rdf:type schema:CreativeWork
197 sg:pub.10.1038/nrc1457 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042257134
198 https://doi.org/10.1038/nrc1457
199 rdf:type schema:CreativeWork
200 sg:pub.10.1038/nrc1691 schema:sameAs https://app.dimensions.ai/details/publication/pub.1052792626
201 https://doi.org/10.1038/nrc1691
202 rdf:type schema:CreativeWork
203 sg:pub.10.1038/nrc3181 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016615579
204 https://doi.org/10.1038/nrc3181
205 rdf:type schema:CreativeWork
206 sg:pub.10.1038/srep18046 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044985306
207 https://doi.org/10.1038/srep18046
208 rdf:type schema:CreativeWork
209 sg:pub.10.1186/1471-2407-10-229 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030456365
210 https://doi.org/10.1186/1471-2407-10-229
211 rdf:type schema:CreativeWork
212 sg:pub.10.1186/1756-6649-9-1 schema:sameAs https://app.dimensions.ai/details/publication/pub.1051028910
213 https://doi.org/10.1186/1756-6649-9-1
214 rdf:type schema:CreativeWork
215 sg:pub.10.1186/s13053-015-0038-x schema:sameAs https://app.dimensions.ai/details/publication/pub.1015885733
216 https://doi.org/10.1186/s13053-015-0038-x
217 rdf:type schema:CreativeWork
218 https://app.dimensions.ai/details/publication/pub.1079293467 schema:CreativeWork
219 https://doi.org/10.1001/jama.2015.16669 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024093685
220 rdf:type schema:CreativeWork
221 https://doi.org/10.1002/cam4.210 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012332812
222 rdf:type schema:CreativeWork
223 https://doi.org/10.1002/ijc.30406 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024554742
224 rdf:type schema:CreativeWork
225 https://doi.org/10.1002/prp2.149 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018270796
226 rdf:type schema:CreativeWork
227 https://doi.org/10.1016/j.chroma.2005.03.070 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016380180
228 rdf:type schema:CreativeWork
229 https://doi.org/10.1016/j.ijrobp.2015.05.037 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021153459
230 rdf:type schema:CreativeWork
231 https://doi.org/10.1016/j.pan.2013.11.009 schema:sameAs https://app.dimensions.ai/details/publication/pub.1000383508
232 rdf:type schema:CreativeWork
233 https://doi.org/10.1016/s1097-2765(00)80035-0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045196719
234 rdf:type schema:CreativeWork
235 https://doi.org/10.1038/emboj.2010.238 schema:sameAs https://app.dimensions.ai/details/publication/pub.1043596363
236 rdf:type schema:CreativeWork
237 https://doi.org/10.1038/msb4100116 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006097382
238 rdf:type schema:CreativeWork
239 https://doi.org/10.1053/j.seminoncol.2014.09.006 schema:sameAs https://app.dimensions.ai/details/publication/pub.1040012676
240 rdf:type schema:CreativeWork
241 https://doi.org/10.1053/j.seminoncol.2014.09.009 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015713508
242 rdf:type schema:CreativeWork
243 https://doi.org/10.1073/pnas.0702916104 schema:sameAs https://app.dimensions.ai/details/publication/pub.1039241372
244 rdf:type schema:CreativeWork
245 https://doi.org/10.1074/jbc.m500963200 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033465522
246 rdf:type schema:CreativeWork
247 https://doi.org/10.1083/jcb.151.7.1381 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002675122
248 rdf:type schema:CreativeWork
249 https://doi.org/10.1093/hmg/ddl002 schema:sameAs https://app.dimensions.ai/details/publication/pub.1037307111
250 rdf:type schema:CreativeWork
251 https://doi.org/10.1093/nar/gkn234 schema:sameAs https://app.dimensions.ai/details/publication/pub.1027599014
252 rdf:type schema:CreativeWork
253 https://doi.org/10.1097/01.jto.0000391367.63882.79 schema:sameAs https://app.dimensions.ai/details/publication/pub.1013764548
254 rdf:type schema:CreativeWork
255 https://doi.org/10.1097/jto.0b013e3181ec809b schema:sameAs https://app.dimensions.ai/details/publication/pub.1014594271
256 rdf:type schema:CreativeWork
257 https://doi.org/10.1101/gad.2053211 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014251409
258 rdf:type schema:CreativeWork
259 https://doi.org/10.1111/nyas.12112 schema:sameAs https://app.dimensions.ai/details/publication/pub.1007050840
260 rdf:type schema:CreativeWork
261 https://doi.org/10.1152/ajpendo.00308.2012 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012620834
262 rdf:type schema:CreativeWork
263 https://doi.org/10.1158/0008-5472.can-04-0083 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010702956
264 rdf:type schema:CreativeWork
265 https://doi.org/10.1158/0008-5472.can-06-2627 schema:sameAs https://app.dimensions.ai/details/publication/pub.1051995727
266 rdf:type schema:CreativeWork
267 https://doi.org/10.1158/0008-5472.can-07-0369 schema:sameAs https://app.dimensions.ai/details/publication/pub.1019813566
268 rdf:type schema:CreativeWork
269 https://doi.org/10.1200/jco.2013.53.1228 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026492122
270 rdf:type schema:CreativeWork
271 https://doi.org/10.1200/jco.2014.55.1929 schema:sameAs https://app.dimensions.ai/details/publication/pub.1050249529
272 rdf:type schema:CreativeWork
273 https://doi.org/10.1371/journal.pone.0125269 schema:sameAs https://app.dimensions.ai/details/publication/pub.1053720068
274 rdf:type schema:CreativeWork
275 https://doi.org/10.18632/oncotarget.11407 schema:sameAs https://app.dimensions.ai/details/publication/pub.1029447102
276 rdf:type schema:CreativeWork
277 https://doi.org/10.18632/oncotarget.6659 schema:sameAs https://app.dimensions.ai/details/publication/pub.1035778473
278 rdf:type schema:CreativeWork
279 https://doi.org/10.3322/caac.21220 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014250067
280 rdf:type schema:CreativeWork
281 https://doi.org/10.3389/fonc.2015.00257 schema:sameAs https://app.dimensions.ai/details/publication/pub.1049126725
282 rdf:type schema:CreativeWork
283 https://www.grid.ac/institutes/grid.267313.2 schema:alternateName The University of Texas Southwestern Medical Center
284 schema:name Division of Molecular Radiation Biology, Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA
285 Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA
286 rdf:type schema:Organization
 




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


...