Tumor-selective use of DNA base excision repair inhibition in pancreatic cancer using the NQO1 bioactivatable drug, β-lapachone View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-12

AUTHORS

Gaurab Chakrabarti, Molly A Silvers, Mariya Ilcheva, Yuliang Liu, Zachary R Moore, Xiuquan Luo, Jinming Gao, Glenda Anderson, Lili Liu, Venetia Sarode, David E Gerber, Sandeep Burma, Ralph J DeBerardinis, Stanton L Gerson, David A Boothman

ABSTRACT

Base excision repair (BER) is an essential pathway for pancreatic ductal adenocarcinoma (PDA) survival. Attempts to target this repair pathway have failed due to lack of tumor-selectivity and very limited efficacy. The NAD(P)H: Quinone Oxidoreductase 1 (NQO1) bioactivatable drug, ß-lapachone (ARQ761 in clinical form), can provide tumor-selective and enhanced synergy with BER inhibition. ß-Lapachone undergoes NQO1-dependent futile redox cycling, generating massive intracellular hydrogen peroxide levels and oxidative DNA lesions that stimulate poly(ADP-ribose) polymerase 1 (PARP1) hyperactivation. Rapid NAD(+)/ATP depletion and programmed necrosis results. To identify BER modulators essential for repair of ß-lapachone-induced DNA base damage, a focused synthetic lethal RNAi screen demonstrated that silencing the BER scaffolding protein, XRCC1, sensitized PDA cells. In contrast, depleting OGG1 N-glycosylase spared cells from ß-lap-induced lethality and blunted PARP1 hyperactivation. Combining ß-lapachone with XRCC1 knockdown or methoxyamine (MeOX), an apyrimidinic/apurinic (AP)-modifying agent, led to NQO1-dependent synergistic killing in PDA, NSCLC, breast and head and neck cancers. OGG1 knockdown, dicoumarol-treatment or NQO1- cancer cells were spared. MeOX + ß-lapachone exposure resulted in elevated DNA double-strand breaks, PARP1 hyperactivation and TUNEL+ programmed necrosis. Combination treatment caused dramatic antitumor activity, enhanced PARP1-hyperactivation in tumor tissue, and improved survival of mice bearing MiaPaca2-derived xenografts, with 33% apparent cures. SIGNIFICANCE: Targeting base excision repair (BER) alone has limited therapeutic potential for pancreatic or other cancers due to a general lack of tumor-selectivity. Here, we present a treatment strategy that makes BER inhibition tumor-selective and NQO1-dependent for therapy of most solid neoplasms, particularly for pancreatic cancer. More... »

PAGES

17066

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/srep17066

DOI

http://dx.doi.org/10.1038/srep17066

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1004097548

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26602448


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": "Autophagy", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Catalase", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Cell Line, Tumor", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Cell Survival", 
        "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 Glycosylases", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "DNA Repair", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "DNA-Binding Proteins", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Dicumarol", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Female", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Humans", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Hydroxylamines", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Mice", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Mice, Nude", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "NAD(P)H Dehydrogenase (Quinone)", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Naphthoquinones", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Pancreatic Neoplasms", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Poly(ADP-ribose) Polymerases", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Reactive Oxygen Species", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Transplantation, Heterologous", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "X-ray Repair Cross Complementing Protein 1", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "The University of Texas Southwestern Medical Center", 
          "id": "https://www.grid.ac/institutes/grid.267313.2", 
          "name": [
            "Departments of Pharmacology, Dallas, TX 75390-8807.", 
            "Radiation Oncology, Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX 75390-8807."
          ], 
          "type": "Organization"
        }, 
        "familyName": "Chakrabarti", 
        "givenName": "Gaurab", 
        "id": "sg:person.01331641251.32", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01331641251.32"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "The University of Texas Southwestern Medical Center", 
          "id": "https://www.grid.ac/institutes/grid.267313.2", 
          "name": [
            "Departments of Pharmacology, Dallas, TX 75390-8807.", 
            "Radiation Oncology, Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX 75390-8807."
          ], 
          "type": "Organization"
        }, 
        "familyName": "Silvers", 
        "givenName": "Molly A", 
        "id": "sg:person.0654761717.26", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0654761717.26"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "The University of Texas Southwestern Medical Center", 
          "id": "https://www.grid.ac/institutes/grid.267313.2", 
          "name": [
            "Radiation Oncology, Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX 75390-8807."
          ], 
          "type": "Organization"
        }, 
        "familyName": "Ilcheva", 
        "givenName": "Mariya", 
        "id": "sg:person.01110057250.04", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01110057250.04"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "The University of Texas Southwestern Medical Center", 
          "id": "https://www.grid.ac/institutes/grid.267313.2", 
          "name": [
            "Departments of Pharmacology, Dallas, TX 75390-8807.", 
            "Radiation Oncology, Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX 75390-8807."
          ], 
          "type": "Organization"
        }, 
        "familyName": "Liu", 
        "givenName": "Yuliang", 
        "id": "sg:person.0665253447.56", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0665253447.56"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "The University of Texas Southwestern Medical Center", 
          "id": "https://www.grid.ac/institutes/grid.267313.2", 
          "name": [
            "Departments of Pharmacology, Dallas, TX 75390-8807.", 
            "Radiation Oncology, Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX 75390-8807."
          ], 
          "type": "Organization"
        }, 
        "familyName": "Moore", 
        "givenName": "Zachary R", 
        "id": "sg:person.01315132032.72", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01315132032.72"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "The University of Texas Southwestern Medical Center", 
          "id": "https://www.grid.ac/institutes/grid.267313.2", 
          "name": [
            "Departments of Pharmacology, Dallas, TX 75390-8807.", 
            "Radiation Oncology, Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX 75390-8807."
          ], 
          "type": "Organization"
        }, 
        "familyName": "Luo", 
        "givenName": "Xiuquan", 
        "id": "sg:person.01200703432.77", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01200703432.77"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "name": [
            "Departments of Pharmacology, Dallas, TX 75390-8807."
          ], 
          "type": "Organization"
        }, 
        "familyName": "Gao", 
        "givenName": "Jinming", 
        "id": "sg:person.0644124020.21", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0644124020.21"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "name": [
            "5 Degrees Bio, San Jose, CA 95113."
          ], 
          "type": "Organization"
        }, 
        "familyName": "Anderson", 
        "givenName": "Glenda", 
        "id": "sg:person.01076020364.48", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01076020364.48"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "name": [
            "Department of Hematology and Oncology, Case Western Reserve Comprehensive Cancer Center, Cleveland, OH 44106."
          ], 
          "type": "Organization"
        }, 
        "familyName": "Liu", 
        "givenName": "Lili", 
        "id": "sg:person.014065446114.29", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014065446114.29"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "The University of Texas Southwestern Medical Center", 
          "id": "https://www.grid.ac/institutes/grid.267313.2", 
          "name": [
            "Department of Pathology, UT Southwestern Medical Center, Dallas, TX 75390-9234."
          ], 
          "type": "Organization"
        }, 
        "familyName": "Sarode", 
        "givenName": "Venetia", 
        "id": "sg:person.01004563354.90", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01004563354.90"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "The University of Texas Southwestern Medical Center", 
          "id": "https://www.grid.ac/institutes/grid.267313.2", 
          "name": [
            "Radiation Oncology, Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX 75390-8807."
          ], 
          "type": "Organization"
        }, 
        "familyName": "Gerber", 
        "givenName": "David E", 
        "id": "sg:person.01236702542.90", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01236702542.90"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "The University of Texas Southwestern Medical Center", 
          "id": "https://www.grid.ac/institutes/grid.267313.2", 
          "name": [
            "Radiation Oncology, Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX 75390-8807."
          ], 
          "type": "Organization"
        }, 
        "familyName": "Burma", 
        "givenName": "Sandeep", 
        "id": "sg:person.01142321463.18", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01142321463.18"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "The University of Texas Southwestern Medical Center", 
          "id": "https://www.grid.ac/institutes/grid.267313.2", 
          "name": [
            "Children's Medical Center Research Institute, UT Southwestern Medical Center, Dallas, TX 75390-8502."
          ], 
          "type": "Organization"
        }, 
        "familyName": "DeBerardinis", 
        "givenName": "Ralph J", 
        "id": "sg:person.014412221657.71", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014412221657.71"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "name": [
            "Department of Hematology and Oncology, Case Western Reserve Comprehensive Cancer Center, Cleveland, OH 44106."
          ], 
          "type": "Organization"
        }, 
        "familyName": "Gerson", 
        "givenName": "Stanton L", 
        "id": "sg:person.016326304537.78", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016326304537.78"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "The University of Texas Southwestern Medical Center", 
          "id": "https://www.grid.ac/institutes/grid.267313.2", 
          "name": [
            "Departments of Pharmacology, Dallas, TX 75390-8807.", 
            "Radiation Oncology, Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX 75390-8807."
          ], 
          "type": "Organization"
        }, 
        "familyName": "Boothman", 
        "givenName": "David A", 
        "id": "sg:person.01240346011.02", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01240346011.02"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "https://doi.org/10.1074/jbc.m603678200", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1000122071"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s13277-014-1792-5", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1001019568", 
          "https://doi.org/10.1007/s13277-014-1792-5"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s13277-014-1792-5", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1001019568", 
          "https://doi.org/10.1007/s13277-014-1792-5"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1074/jbc.275.8.5416", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1002383137"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/0008-5472.can-10-1418", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1002809819"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.dnarep.2003.10.002", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1002875812"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1074/jbc.m111.255869", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1003809022"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s12032-012-0300-2", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1004067008", 
          "https://doi.org/10.1007/s12032-012-0300-2"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s12032-012-0300-2", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1004067008", 
          "https://doi.org/10.1007/s12032-012-0300-2"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.celrep.2014.08.036", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1004263561"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1089/ars.2013.5462", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1008331743"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1074/jbc.m100730200", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1014951809"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.mrfmmm.2010.01.016", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1015955943"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/nar/gku288", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1016385083"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.mrgentox.2013.08.003", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1016685524"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1371/journal.pone.0031507", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1016914910"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/nar/gkt076", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1019079385"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s0300-483x(03)00289-0", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1020630107"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s0300-483x(03)00289-0", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1020630107"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.jchromb.2008.07.031", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1021392912"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.2147/pgpm.s20317", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1022400850"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/nar/gkt025", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1022694231"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s0959-8049(14)70379-x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1023166900"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s0378-4347(96)00497-5", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1023208552"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1101/gad.1199904", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1023234677"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.dnarep.2007.01.009", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1024346180"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1101/cshperspect.a012583", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1025587944"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/1535-7163.mct-12-0962", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1026660995"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/cddis.2014.564", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1027444714", 
          "https://doi.org/10.1038/cddis.2014.564"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1593/neo.07397", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1028089677"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1038/sj.emboj.7601975", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1028914438"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/1471-2105-8-449", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1031423044", 
          "https://doi.org/10.1186/1471-2105-8-449"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/35002510", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1031442985", 
          "https://doi.org/10.1038/35002510"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/35002510", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1031442985", 
          "https://doi.org/10.1038/35002510"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/nar/gkg761", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1031640040"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/1078-0432.ccr-06-1595", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1032454850"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1101/gad.215533.113", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1032822132"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1074/jbc.m114.624718", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1034729289"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/1078-0432.ccr-06-1920", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1035145279"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.bbcan.2014.04.002", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1035474026"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/0008-5472.can-07-0935", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1037114554"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/biostatistics/4.2.249", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1037543114"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1073/pnas.0702176104", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1039542715"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/1078-0432.ccr-10-1983", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1040369941"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/ppo.0b013e3181d78223", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1043808494"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/ppo.0b013e3181d78223", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1043808494"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/ppo.0b013e3181d78223", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1043808494"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.dnarep.2013.06.004", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1045659147"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1073/pnas.1009182107", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1046072570"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/0008-5472.can-11-3135", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1047454055"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1113/expphysiol.2006.033506", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1047545158"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s10238-012-0201-x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1048653746", 
          "https://doi.org/10.1007/s10238-012-0201-x"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1074/jbc.m601162200", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1048969916"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/0008-5472.can-09-3995", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1050759903"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/0008-5472.can-14-0562", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1051956801"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/0008-5472.can-14-0562", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1051956801"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1073/pnas.1405158111", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1052452630"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/pai.0b013e31802e91d0", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1053392165"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/pai.0b013e31802e91d0", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1053392165"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1126/science.1072221", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1062446588"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1075123990", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1076863870", 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2015-12", 
    "datePublishedReg": "2015-12-01", 
    "description": "Base excision repair (BER) is an essential pathway for pancreatic ductal adenocarcinoma (PDA) survival. Attempts to target this repair pathway have failed due to lack of tumor-selectivity and very limited efficacy. The\nNAD(P)H: Quinone Oxidoreductase 1 (NQO1) bioactivatable drug, \u00df-lapachone (ARQ761 in clinical form), can provide tumor-selective and enhanced synergy with BER inhibition. \u00df-Lapachone undergoes NQO1-dependent futile redox cycling, generating massive intracellular hydrogen peroxide levels and oxidative DNA lesions that stimulate poly(ADP-ribose) polymerase 1 (PARP1) hyperactivation. Rapid NAD(+)/ATP depletion and programmed necrosis results. To identify BER modulators essential for repair of \u00df-lapachone-induced DNA base damage, a focused synthetic lethal RNAi screen demonstrated that silencing the BER scaffolding protein, XRCC1, sensitized PDA cells. In contrast, depleting OGG1 N-glycosylase spared cells from \u00df-lap-induced lethality and blunted PARP1 hyperactivation. Combining \u00df-lapachone with XRCC1 knockdown or methoxyamine (MeOX), an apyrimidinic/apurinic (AP)-modifying agent, led to NQO1-dependent synergistic killing in PDA, NSCLC, breast and head and neck cancers. OGG1 knockdown, dicoumarol-treatment or NQO1- cancer cells were spared. MeOX + \u00df-lapachone exposure resulted in elevated DNA double-strand breaks, PARP1 hyperactivation and TUNEL+ programmed necrosis. Combination treatment caused dramatic antitumor activity, enhanced PARP1-hyperactivation in tumor tissue, and improved survival of mice bearing MiaPaca2-derived xenografts, with 33% apparent cures.\nSIGNIFICANCE: Targeting base excision repair (BER) alone has limited therapeutic potential for pancreatic or other cancers due to a general lack of tumor-selectivity. Here, we present a treatment strategy that makes BER inhibition tumor-selective and NQO1-dependent for therapy of most solid neoplasms, particularly for pancreatic cancer.", 
    "genre": "research_article", 
    "id": "sg:pub.10.1038/srep17066", 
    "inLanguage": [
      "en"
    ], 
    "isAccessibleForFree": true, 
    "isFundedItemOf": [
      {
        "id": "sg:grant.2438881", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2476986", 
        "type": "MonetaryGrant"
      }
    ], 
    "isPartOf": [
      {
        "id": "sg:journal.1045337", 
        "issn": [
          "2045-2322"
        ], 
        "name": "Scientific Reports", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "1", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "5"
      }
    ], 
    "name": "Tumor-selective use of DNA base excision repair inhibition in pancreatic cancer using the NQO1 bioactivatable drug, \u03b2-lapachone", 
    "pagination": "17066", 
    "productId": [
      {
        "name": "readcube_id", 
        "type": "PropertyValue", 
        "value": [
          "138655ca95397a5c5db4ce6a701dcc67ceaed14ab478892efc3a4a3aae5809ed"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "26602448"
        ]
      }, 
      {
        "name": "nlm_unique_id", 
        "type": "PropertyValue", 
        "value": [
          "101563288"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1038/srep17066"
        ]
      }, 
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1004097548"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1038/srep17066", 
      "https://app.dimensions.ai/details/publication/pub.1004097548"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2019-04-11T01:18", 
    "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_8697_00000580.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "http://www.nature.com/srep/2015/151125/srep17066/full/srep17066.html"
  }
]
 

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/srep17066'

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/srep17066'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/srep17066'

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

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/srep17066'


 

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

435 TRIPLES      21 PREDICATES      105 URIs      43 LITERALS      31 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1038/srep17066 schema:about N23e27739274745f79b0fba773ddd374e
2 N26bb58cc1ccc4d19aaefca289417d9e0
3 N27d57f7ca133468f8cceef38171198f1
4 N2ff4d4fee025479a8d53d386e54cc6d6
5 N34b98a92555a4100a7ee7541bcdd2ea4
6 N37df825ce64042b8a147e774d1815282
7 N3ced6628b034495eb83ccc4795d0644e
8 N41eac608d9e84a70ad42b0ebb8fa4eb1
9 N46328df59f144b8793907d2932599148
10 N4e67df470c224cb5897b1f0c023bb7a1
11 N60d877a518e246828859d32535c535a0
12 N6462025c4b14498a8198c3b45be2e020
13 N6861953caf0a4c2fa85b128d405c4d84
14 N723f0a985c10441c85b39b5f35dd4d48
15 N7921283ec9e04e699340948d2b777d2b
16 N84927683863345bb83fd93f9c77a4f73
17 N86391cc209fe4e2a9acde16c038f3e98
18 N9ebeeb2c02794ecd83e3cb308475c511
19 Na5bdba9b70a046b69636842b115559fa
20 Ne4637fbd7cca4200b4c4ede2b6f10b31
21 Nf784795ffd0442ce8f1411abdb17e4ce
22 Nf78faa9d89a7400fa4f26cbd62478c75
23 anzsrc-for:11
24 anzsrc-for:1112
25 schema:author N305a0aafe9774a88b71c5c6f3628acb6
26 schema:citation sg:pub.10.1007/s10238-012-0201-x
27 sg:pub.10.1007/s12032-012-0300-2
28 sg:pub.10.1007/s13277-014-1792-5
29 sg:pub.10.1038/35002510
30 sg:pub.10.1038/cddis.2014.564
31 sg:pub.10.1186/1471-2105-8-449
32 https://app.dimensions.ai/details/publication/pub.1075123990
33 https://app.dimensions.ai/details/publication/pub.1076863870
34 https://doi.org/10.1016/j.bbcan.2014.04.002
35 https://doi.org/10.1016/j.celrep.2014.08.036
36 https://doi.org/10.1016/j.dnarep.2003.10.002
37 https://doi.org/10.1016/j.dnarep.2007.01.009
38 https://doi.org/10.1016/j.dnarep.2013.06.004
39 https://doi.org/10.1016/j.jchromb.2008.07.031
40 https://doi.org/10.1016/j.mrfmmm.2010.01.016
41 https://doi.org/10.1016/j.mrgentox.2013.08.003
42 https://doi.org/10.1016/s0300-483x(03)00289-0
43 https://doi.org/10.1016/s0378-4347(96)00497-5
44 https://doi.org/10.1016/s0959-8049(14)70379-x
45 https://doi.org/10.1038/sj.emboj.7601975
46 https://doi.org/10.1073/pnas.0702176104
47 https://doi.org/10.1073/pnas.1009182107
48 https://doi.org/10.1073/pnas.1405158111
49 https://doi.org/10.1074/jbc.275.8.5416
50 https://doi.org/10.1074/jbc.m100730200
51 https://doi.org/10.1074/jbc.m111.255869
52 https://doi.org/10.1074/jbc.m114.624718
53 https://doi.org/10.1074/jbc.m601162200
54 https://doi.org/10.1074/jbc.m603678200
55 https://doi.org/10.1089/ars.2013.5462
56 https://doi.org/10.1093/biostatistics/4.2.249
57 https://doi.org/10.1093/nar/gkg761
58 https://doi.org/10.1093/nar/gkt025
59 https://doi.org/10.1093/nar/gkt076
60 https://doi.org/10.1093/nar/gku288
61 https://doi.org/10.1097/pai.0b013e31802e91d0
62 https://doi.org/10.1097/ppo.0b013e3181d78223
63 https://doi.org/10.1101/cshperspect.a012583
64 https://doi.org/10.1101/gad.1199904
65 https://doi.org/10.1101/gad.215533.113
66 https://doi.org/10.1113/expphysiol.2006.033506
67 https://doi.org/10.1126/science.1072221
68 https://doi.org/10.1158/0008-5472.can-07-0935
69 https://doi.org/10.1158/0008-5472.can-09-3995
70 https://doi.org/10.1158/0008-5472.can-10-1418
71 https://doi.org/10.1158/0008-5472.can-11-3135
72 https://doi.org/10.1158/0008-5472.can-14-0562
73 https://doi.org/10.1158/1078-0432.ccr-06-1595
74 https://doi.org/10.1158/1078-0432.ccr-06-1920
75 https://doi.org/10.1158/1078-0432.ccr-10-1983
76 https://doi.org/10.1158/1535-7163.mct-12-0962
77 https://doi.org/10.1371/journal.pone.0031507
78 https://doi.org/10.1593/neo.07397
79 https://doi.org/10.2147/pgpm.s20317
80 schema:datePublished 2015-12
81 schema:datePublishedReg 2015-12-01
82 schema:description Base excision repair (BER) is an essential pathway for pancreatic ductal adenocarcinoma (PDA) survival. Attempts to target this repair pathway have failed due to lack of tumor-selectivity and very limited efficacy. The NAD(P)H: Quinone Oxidoreductase 1 (NQO1) bioactivatable drug, ß-lapachone (ARQ761 in clinical form), can provide tumor-selective and enhanced synergy with BER inhibition. ß-Lapachone undergoes NQO1-dependent futile redox cycling, generating massive intracellular hydrogen peroxide levels and oxidative DNA lesions that stimulate poly(ADP-ribose) polymerase 1 (PARP1) hyperactivation. Rapid NAD(+)/ATP depletion and programmed necrosis results. To identify BER modulators essential for repair of ß-lapachone-induced DNA base damage, a focused synthetic lethal RNAi screen demonstrated that silencing the BER scaffolding protein, XRCC1, sensitized PDA cells. In contrast, depleting OGG1 N-glycosylase spared cells from ß-lap-induced lethality and blunted PARP1 hyperactivation. Combining ß-lapachone with XRCC1 knockdown or methoxyamine (MeOX), an apyrimidinic/apurinic (AP)-modifying agent, led to NQO1-dependent synergistic killing in PDA, NSCLC, breast and head and neck cancers. OGG1 knockdown, dicoumarol-treatment or NQO1- cancer cells were spared. MeOX + ß-lapachone exposure resulted in elevated DNA double-strand breaks, PARP1 hyperactivation and TUNEL+ programmed necrosis. Combination treatment caused dramatic antitumor activity, enhanced PARP1-hyperactivation in tumor tissue, and improved survival of mice bearing MiaPaca2-derived xenografts, with 33% apparent cures. SIGNIFICANCE: Targeting base excision repair (BER) alone has limited therapeutic potential for pancreatic or other cancers due to a general lack of tumor-selectivity. Here, we present a treatment strategy that makes BER inhibition tumor-selective and NQO1-dependent for therapy of most solid neoplasms, particularly for pancreatic cancer.
83 schema:genre research_article
84 schema:inLanguage en
85 schema:isAccessibleForFree true
86 schema:isPartOf N40b85dd9cebb4c2ba9d0ae784e12954f
87 N49d59fca407247058d8ae3a5f96f9218
88 sg:journal.1045337
89 schema:name Tumor-selective use of DNA base excision repair inhibition in pancreatic cancer using the NQO1 bioactivatable drug, β-lapachone
90 schema:pagination 17066
91 schema:productId N1d16ca1d85444318a1d364291fa209aa
92 N2e195da2bdf84f0797c7c0bc02d8d330
93 N43da5ec54c544d2a92716fc997c008b3
94 N537ea5135d404c608651b93a3fd850fc
95 Nb3d8a1b729ec42e095bc44913b2f1884
96 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004097548
97 https://doi.org/10.1038/srep17066
98 schema:sdDatePublished 2019-04-11T01:18
99 schema:sdLicense https://scigraph.springernature.com/explorer/license/
100 schema:sdPublisher Na16ad8b02ce44c229c569f5dd5b42de8
101 schema:url http://www.nature.com/srep/2015/151125/srep17066/full/srep17066.html
102 sgo:license sg:explorer/license/
103 sgo:sdDataset articles
104 rdf:type schema:ScholarlyArticle
105 N1d16ca1d85444318a1d364291fa209aa schema:name readcube_id
106 schema:value 138655ca95397a5c5db4ce6a701dcc67ceaed14ab478892efc3a4a3aae5809ed
107 rdf:type schema:PropertyValue
108 N23b997255aaf4e49a7dcf01acee27cb8 schema:name Department of Hematology and Oncology, Case Western Reserve Comprehensive Cancer Center, Cleveland, OH 44106.
109 rdf:type schema:Organization
110 N23e27739274745f79b0fba773ddd374e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
111 schema:name Humans
112 rdf:type schema:DefinedTerm
113 N26bb58cc1ccc4d19aaefca289417d9e0 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
114 schema:name DNA Repair
115 rdf:type schema:DefinedTerm
116 N27193b6da41c4396a8a8b7e77b3d5c4b rdf:first sg:person.01315132032.72
117 rdf:rest N984c5543451f4315a975ab5bacc042af
118 N27d57f7ca133468f8cceef38171198f1 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
119 schema:name Cell Survival
120 rdf:type schema:DefinedTerm
121 N29f7d44a08c84eaba80922e24016693d rdf:first sg:person.01004563354.90
122 rdf:rest N2bf917c31c07411694ede656149b43e4
123 N29fba3b5bd8a4d729943a453e3750acb rdf:first sg:person.01240346011.02
124 rdf:rest rdf:nil
125 N2bf917c31c07411694ede656149b43e4 rdf:first sg:person.01236702542.90
126 rdf:rest Ne5893ff099bb4dc9bfd5b4fea123b137
127 N2e195da2bdf84f0797c7c0bc02d8d330 schema:name dimensions_id
128 schema:value pub.1004097548
129 rdf:type schema:PropertyValue
130 N2ff4d4fee025479a8d53d386e54cc6d6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
131 schema:name Reactive Oxygen Species
132 rdf:type schema:DefinedTerm
133 N305a0aafe9774a88b71c5c6f3628acb6 rdf:first sg:person.01331641251.32
134 rdf:rest Na616cb5d5ac24029acef287b04ee8c0b
135 N34b98a92555a4100a7ee7541bcdd2ea4 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
136 schema:name Mice
137 rdf:type schema:DefinedTerm
138 N37df825ce64042b8a147e774d1815282 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
139 schema:name Dicumarol
140 rdf:type schema:DefinedTerm
141 N39f6281179894c93bdc7c31e635b2e98 rdf:first sg:person.01076020364.48
142 rdf:rest N73be11d3094c4cd382b80ef0ac4b4f8f
143 N3ced6628b034495eb83ccc4795d0644e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
144 schema:name DNA-Binding Proteins
145 rdf:type schema:DefinedTerm
146 N40b85dd9cebb4c2ba9d0ae784e12954f schema:issueNumber 1
147 rdf:type schema:PublicationIssue
148 N41eac608d9e84a70ad42b0ebb8fa4eb1 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
149 schema:name Catalase
150 rdf:type schema:DefinedTerm
151 N42c5d79777054754a34c392b9d68a2d5 schema:name Departments of Pharmacology, Dallas, TX 75390-8807.
152 rdf:type schema:Organization
153 N43da5ec54c544d2a92716fc997c008b3 schema:name nlm_unique_id
154 schema:value 101563288
155 rdf:type schema:PropertyValue
156 N46328df59f144b8793907d2932599148 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
157 schema:name Animals
158 rdf:type schema:DefinedTerm
159 N49d59fca407247058d8ae3a5f96f9218 schema:volumeNumber 5
160 rdf:type schema:PublicationVolume
161 N4e67df470c224cb5897b1f0c023bb7a1 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
162 schema:name Poly(ADP-ribose) Polymerases
163 rdf:type schema:DefinedTerm
164 N537ea5135d404c608651b93a3fd850fc schema:name doi
165 schema:value 10.1038/srep17066
166 rdf:type schema:PropertyValue
167 N6030915cac51475582b1cb55ee93b073 schema:name 5 Degrees Bio, San Jose, CA 95113.
168 rdf:type schema:Organization
169 N60d877a518e246828859d32535c535a0 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
170 schema:name DNA Breaks, Double-Stranded
171 rdf:type schema:DefinedTerm
172 N6462025c4b14498a8198c3b45be2e020 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
173 schema:name Hydroxylamines
174 rdf:type schema:DefinedTerm
175 N6861953caf0a4c2fa85b128d405c4d84 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
176 schema:name NAD(P)H Dehydrogenase (Quinone)
177 rdf:type schema:DefinedTerm
178 N723f0a985c10441c85b39b5f35dd4d48 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
179 schema:name Autophagy
180 rdf:type schema:DefinedTerm
181 N73be11d3094c4cd382b80ef0ac4b4f8f rdf:first sg:person.014065446114.29
182 rdf:rest N29f7d44a08c84eaba80922e24016693d
183 N7921283ec9e04e699340948d2b777d2b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
184 schema:name Mice, Nude
185 rdf:type schema:DefinedTerm
186 N796da959ed7f47d6956af764e1c33e5a rdf:first sg:person.01110057250.04
187 rdf:rest Nfeb355cc3e884ca6bf3fcfc2b9e6c05c
188 N84927683863345bb83fd93f9c77a4f73 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
189 schema:name Female
190 rdf:type schema:DefinedTerm
191 N86391cc209fe4e2a9acde16c038f3e98 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
192 schema:name Transplantation, Heterologous
193 rdf:type schema:DefinedTerm
194 N866240a290bc4420aab7d135ea84e2d1 rdf:first sg:person.016326304537.78
195 rdf:rest N29fba3b5bd8a4d729943a453e3750acb
196 N91baf04bb10a4ce997d03fe5defc6925 schema:name Department of Hematology and Oncology, Case Western Reserve Comprehensive Cancer Center, Cleveland, OH 44106.
197 rdf:type schema:Organization
198 N984c5543451f4315a975ab5bacc042af rdf:first sg:person.01200703432.77
199 rdf:rest Nb68bbaa7b9ce4380b44e409be15e2c27
200 N9ebeeb2c02794ecd83e3cb308475c511 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
201 schema:name Pancreatic Neoplasms
202 rdf:type schema:DefinedTerm
203 Na16ad8b02ce44c229c569f5dd5b42de8 schema:name Springer Nature - SN SciGraph project
204 rdf:type schema:Organization
205 Na5bdba9b70a046b69636842b115559fa schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
206 schema:name DNA Glycosylases
207 rdf:type schema:DefinedTerm
208 Na616cb5d5ac24029acef287b04ee8c0b rdf:first sg:person.0654761717.26
209 rdf:rest N796da959ed7f47d6956af764e1c33e5a
210 Nb3d8a1b729ec42e095bc44913b2f1884 schema:name pubmed_id
211 schema:value 26602448
212 rdf:type schema:PropertyValue
213 Nb68bbaa7b9ce4380b44e409be15e2c27 rdf:first sg:person.0644124020.21
214 rdf:rest N39f6281179894c93bdc7c31e635b2e98
215 Nb7d1f914860f45b0aef2de6014ed131e rdf:first sg:person.014412221657.71
216 rdf:rest N866240a290bc4420aab7d135ea84e2d1
217 Ne4637fbd7cca4200b4c4ede2b6f10b31 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
218 schema:name X-ray Repair Cross Complementing Protein 1
219 rdf:type schema:DefinedTerm
220 Ne5893ff099bb4dc9bfd5b4fea123b137 rdf:first sg:person.01142321463.18
221 rdf:rest Nb7d1f914860f45b0aef2de6014ed131e
222 Nf784795ffd0442ce8f1411abdb17e4ce schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
223 schema:name Cell Line, Tumor
224 rdf:type schema:DefinedTerm
225 Nf78faa9d89a7400fa4f26cbd62478c75 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
226 schema:name Naphthoquinones
227 rdf:type schema:DefinedTerm
228 Nfeb355cc3e884ca6bf3fcfc2b9e6c05c rdf:first sg:person.0665253447.56
229 rdf:rest N27193b6da41c4396a8a8b7e77b3d5c4b
230 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
231 schema:name Medical and Health Sciences
232 rdf:type schema:DefinedTerm
233 anzsrc-for:1112 schema:inDefinedTermSet anzsrc-for:
234 schema:name Oncology and Carcinogenesis
235 rdf:type schema:DefinedTerm
236 sg:grant.2438881 http://pending.schema.org/fundedItem sg:pub.10.1038/srep17066
237 rdf:type schema:MonetaryGrant
238 sg:grant.2476986 http://pending.schema.org/fundedItem sg:pub.10.1038/srep17066
239 rdf:type schema:MonetaryGrant
240 sg:journal.1045337 schema:issn 2045-2322
241 schema:name Scientific Reports
242 rdf:type schema:Periodical
243 sg:person.01004563354.90 schema:affiliation https://www.grid.ac/institutes/grid.267313.2
244 schema:familyName Sarode
245 schema:givenName Venetia
246 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01004563354.90
247 rdf:type schema:Person
248 sg:person.01076020364.48 schema:affiliation N6030915cac51475582b1cb55ee93b073
249 schema:familyName Anderson
250 schema:givenName Glenda
251 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01076020364.48
252 rdf:type schema:Person
253 sg:person.01110057250.04 schema:affiliation https://www.grid.ac/institutes/grid.267313.2
254 schema:familyName Ilcheva
255 schema:givenName Mariya
256 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01110057250.04
257 rdf:type schema:Person
258 sg:person.01142321463.18 schema:affiliation https://www.grid.ac/institutes/grid.267313.2
259 schema:familyName Burma
260 schema:givenName Sandeep
261 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01142321463.18
262 rdf:type schema:Person
263 sg:person.01200703432.77 schema:affiliation https://www.grid.ac/institutes/grid.267313.2
264 schema:familyName Luo
265 schema:givenName Xiuquan
266 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01200703432.77
267 rdf:type schema:Person
268 sg:person.01236702542.90 schema:affiliation https://www.grid.ac/institutes/grid.267313.2
269 schema:familyName Gerber
270 schema:givenName David E
271 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01236702542.90
272 rdf:type schema:Person
273 sg:person.01240346011.02 schema:affiliation https://www.grid.ac/institutes/grid.267313.2
274 schema:familyName Boothman
275 schema:givenName David A
276 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01240346011.02
277 rdf:type schema:Person
278 sg:person.01315132032.72 schema:affiliation https://www.grid.ac/institutes/grid.267313.2
279 schema:familyName Moore
280 schema:givenName Zachary R
281 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01315132032.72
282 rdf:type schema:Person
283 sg:person.01331641251.32 schema:affiliation https://www.grid.ac/institutes/grid.267313.2
284 schema:familyName Chakrabarti
285 schema:givenName Gaurab
286 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01331641251.32
287 rdf:type schema:Person
288 sg:person.014065446114.29 schema:affiliation N91baf04bb10a4ce997d03fe5defc6925
289 schema:familyName Liu
290 schema:givenName Lili
291 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014065446114.29
292 rdf:type schema:Person
293 sg:person.014412221657.71 schema:affiliation https://www.grid.ac/institutes/grid.267313.2
294 schema:familyName DeBerardinis
295 schema:givenName Ralph J
296 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014412221657.71
297 rdf:type schema:Person
298 sg:person.016326304537.78 schema:affiliation N23b997255aaf4e49a7dcf01acee27cb8
299 schema:familyName Gerson
300 schema:givenName Stanton L
301 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016326304537.78
302 rdf:type schema:Person
303 sg:person.0644124020.21 schema:affiliation N42c5d79777054754a34c392b9d68a2d5
304 schema:familyName Gao
305 schema:givenName Jinming
306 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0644124020.21
307 rdf:type schema:Person
308 sg:person.0654761717.26 schema:affiliation https://www.grid.ac/institutes/grid.267313.2
309 schema:familyName Silvers
310 schema:givenName Molly A
311 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0654761717.26
312 rdf:type schema:Person
313 sg:person.0665253447.56 schema:affiliation https://www.grid.ac/institutes/grid.267313.2
314 schema:familyName Liu
315 schema:givenName Yuliang
316 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0665253447.56
317 rdf:type schema:Person
318 sg:pub.10.1007/s10238-012-0201-x schema:sameAs https://app.dimensions.ai/details/publication/pub.1048653746
319 https://doi.org/10.1007/s10238-012-0201-x
320 rdf:type schema:CreativeWork
321 sg:pub.10.1007/s12032-012-0300-2 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004067008
322 https://doi.org/10.1007/s12032-012-0300-2
323 rdf:type schema:CreativeWork
324 sg:pub.10.1007/s13277-014-1792-5 schema:sameAs https://app.dimensions.ai/details/publication/pub.1001019568
325 https://doi.org/10.1007/s13277-014-1792-5
326 rdf:type schema:CreativeWork
327 sg:pub.10.1038/35002510 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031442985
328 https://doi.org/10.1038/35002510
329 rdf:type schema:CreativeWork
330 sg:pub.10.1038/cddis.2014.564 schema:sameAs https://app.dimensions.ai/details/publication/pub.1027444714
331 https://doi.org/10.1038/cddis.2014.564
332 rdf:type schema:CreativeWork
333 sg:pub.10.1186/1471-2105-8-449 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031423044
334 https://doi.org/10.1186/1471-2105-8-449
335 rdf:type schema:CreativeWork
336 https://app.dimensions.ai/details/publication/pub.1075123990 schema:CreativeWork
337 https://app.dimensions.ai/details/publication/pub.1076863870 schema:CreativeWork
338 https://doi.org/10.1016/j.bbcan.2014.04.002 schema:sameAs https://app.dimensions.ai/details/publication/pub.1035474026
339 rdf:type schema:CreativeWork
340 https://doi.org/10.1016/j.celrep.2014.08.036 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004263561
341 rdf:type schema:CreativeWork
342 https://doi.org/10.1016/j.dnarep.2003.10.002 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002875812
343 rdf:type schema:CreativeWork
344 https://doi.org/10.1016/j.dnarep.2007.01.009 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024346180
345 rdf:type schema:CreativeWork
346 https://doi.org/10.1016/j.dnarep.2013.06.004 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045659147
347 rdf:type schema:CreativeWork
348 https://doi.org/10.1016/j.jchromb.2008.07.031 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021392912
349 rdf:type schema:CreativeWork
350 https://doi.org/10.1016/j.mrfmmm.2010.01.016 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015955943
351 rdf:type schema:CreativeWork
352 https://doi.org/10.1016/j.mrgentox.2013.08.003 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016685524
353 rdf:type schema:CreativeWork
354 https://doi.org/10.1016/s0300-483x(03)00289-0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1020630107
355 rdf:type schema:CreativeWork
356 https://doi.org/10.1016/s0378-4347(96)00497-5 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023208552
357 rdf:type schema:CreativeWork
358 https://doi.org/10.1016/s0959-8049(14)70379-x schema:sameAs https://app.dimensions.ai/details/publication/pub.1023166900
359 rdf:type schema:CreativeWork
360 https://doi.org/10.1038/sj.emboj.7601975 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028914438
361 rdf:type schema:CreativeWork
362 https://doi.org/10.1073/pnas.0702176104 schema:sameAs https://app.dimensions.ai/details/publication/pub.1039542715
363 rdf:type schema:CreativeWork
364 https://doi.org/10.1073/pnas.1009182107 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046072570
365 rdf:type schema:CreativeWork
366 https://doi.org/10.1073/pnas.1405158111 schema:sameAs https://app.dimensions.ai/details/publication/pub.1052452630
367 rdf:type schema:CreativeWork
368 https://doi.org/10.1074/jbc.275.8.5416 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002383137
369 rdf:type schema:CreativeWork
370 https://doi.org/10.1074/jbc.m100730200 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014951809
371 rdf:type schema:CreativeWork
372 https://doi.org/10.1074/jbc.m111.255869 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003809022
373 rdf:type schema:CreativeWork
374 https://doi.org/10.1074/jbc.m114.624718 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034729289
375 rdf:type schema:CreativeWork
376 https://doi.org/10.1074/jbc.m601162200 schema:sameAs https://app.dimensions.ai/details/publication/pub.1048969916
377 rdf:type schema:CreativeWork
378 https://doi.org/10.1074/jbc.m603678200 schema:sameAs https://app.dimensions.ai/details/publication/pub.1000122071
379 rdf:type schema:CreativeWork
380 https://doi.org/10.1089/ars.2013.5462 schema:sameAs https://app.dimensions.ai/details/publication/pub.1008331743
381 rdf:type schema:CreativeWork
382 https://doi.org/10.1093/biostatistics/4.2.249 schema:sameAs https://app.dimensions.ai/details/publication/pub.1037543114
383 rdf:type schema:CreativeWork
384 https://doi.org/10.1093/nar/gkg761 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031640040
385 rdf:type schema:CreativeWork
386 https://doi.org/10.1093/nar/gkt025 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022694231
387 rdf:type schema:CreativeWork
388 https://doi.org/10.1093/nar/gkt076 schema:sameAs https://app.dimensions.ai/details/publication/pub.1019079385
389 rdf:type schema:CreativeWork
390 https://doi.org/10.1093/nar/gku288 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016385083
391 rdf:type schema:CreativeWork
392 https://doi.org/10.1097/pai.0b013e31802e91d0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1053392165
393 rdf:type schema:CreativeWork
394 https://doi.org/10.1097/ppo.0b013e3181d78223 schema:sameAs https://app.dimensions.ai/details/publication/pub.1043808494
395 rdf:type schema:CreativeWork
396 https://doi.org/10.1101/cshperspect.a012583 schema:sameAs https://app.dimensions.ai/details/publication/pub.1025587944
397 rdf:type schema:CreativeWork
398 https://doi.org/10.1101/gad.1199904 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023234677
399 rdf:type schema:CreativeWork
400 https://doi.org/10.1101/gad.215533.113 schema:sameAs https://app.dimensions.ai/details/publication/pub.1032822132
401 rdf:type schema:CreativeWork
402 https://doi.org/10.1113/expphysiol.2006.033506 schema:sameAs https://app.dimensions.ai/details/publication/pub.1047545158
403 rdf:type schema:CreativeWork
404 https://doi.org/10.1126/science.1072221 schema:sameAs https://app.dimensions.ai/details/publication/pub.1062446588
405 rdf:type schema:CreativeWork
406 https://doi.org/10.1158/0008-5472.can-07-0935 schema:sameAs https://app.dimensions.ai/details/publication/pub.1037114554
407 rdf:type schema:CreativeWork
408 https://doi.org/10.1158/0008-5472.can-09-3995 schema:sameAs https://app.dimensions.ai/details/publication/pub.1050759903
409 rdf:type schema:CreativeWork
410 https://doi.org/10.1158/0008-5472.can-10-1418 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002809819
411 rdf:type schema:CreativeWork
412 https://doi.org/10.1158/0008-5472.can-11-3135 schema:sameAs https://app.dimensions.ai/details/publication/pub.1047454055
413 rdf:type schema:CreativeWork
414 https://doi.org/10.1158/0008-5472.can-14-0562 schema:sameAs https://app.dimensions.ai/details/publication/pub.1051956801
415 rdf:type schema:CreativeWork
416 https://doi.org/10.1158/1078-0432.ccr-06-1595 schema:sameAs https://app.dimensions.ai/details/publication/pub.1032454850
417 rdf:type schema:CreativeWork
418 https://doi.org/10.1158/1078-0432.ccr-06-1920 schema:sameAs https://app.dimensions.ai/details/publication/pub.1035145279
419 rdf:type schema:CreativeWork
420 https://doi.org/10.1158/1078-0432.ccr-10-1983 schema:sameAs https://app.dimensions.ai/details/publication/pub.1040369941
421 rdf:type schema:CreativeWork
422 https://doi.org/10.1158/1535-7163.mct-12-0962 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026660995
423 rdf:type schema:CreativeWork
424 https://doi.org/10.1371/journal.pone.0031507 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016914910
425 rdf:type schema:CreativeWork
426 https://doi.org/10.1593/neo.07397 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028089677
427 rdf:type schema:CreativeWork
428 https://doi.org/10.2147/pgpm.s20317 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022400850
429 rdf:type schema:CreativeWork
430 https://www.grid.ac/institutes/grid.267313.2 schema:alternateName The University of Texas Southwestern Medical Center
431 schema:name Children's Medical Center Research Institute, UT Southwestern Medical Center, Dallas, TX 75390-8502.
432 Department of Pathology, UT Southwestern Medical Center, Dallas, TX 75390-9234.
433 Departments of Pharmacology, Dallas, TX 75390-8807.
434 Radiation Oncology, Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX 75390-8807.
435 rdf:type schema:Organization
 




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


...