Treatment of a chemoresistant neuroblastoma cell line with the antimalarial ozonide OZ513 View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-12

AUTHORS

Don W. Coulter, Timothy R. McGuire, John G. Sharp, Erin M. McIntyre, Yuxiang Dong, Xiaofang Wang, Shawn Gray, Gracey R. Alexander, Nagendra K. Chatuverdi, Shantaram S. Joshi, Xiaoyu Chen, Jonathan L. Vennerstrom

ABSTRACT

BACKGROUND: Evaluate the anti-tumor activity of ozonide antimalarials using a chemoresistant neuroblastoma cell line, BE (2)-c. METHODS: The activity of 12 ozonides, artemisinin, and two semisynthetic artemisinins were tested for activity against two neuroblastoma cell-lines (BE (2)-c and IMR-32) and the Ewing's Sarcoma cell line A673 in an MTT viability assay. Time course data indicated that peak effect was seen 18 h after the start of treatment thus 18 h pre-treatment was used for all subsequent experiments. The most active ozonide (OZ513) was assessed in a propidium iodide cell cycle flow cytometry analysis which measured cell cycle transit and apoptosis. Metabolic effects of OZ513 in BE (2)-c cells was evaluated. Western blots for the apoptotic proteins cleaved capase-3 and cleaved PARP, the highly amplified oncogene MYCN, and the cell cycle regulator CyclinD1, were performed. These in-vitro experiments were followed by an in-vivo experiment in which NOD-scid gamma immunodeficient mice were injected subcutaneously with 1 × 106 BE (2)-c cells followed by immediate treatment with 50-100 mg/kg/day doses of OZ513 administered IP three times per week out to 23 days after injection of tumor. Incidence of tumor development, time to tumor development, and rate of tumor growth were assessed in DMSO treated controls (N = 6), and OZ513 treated mice (N = 5). RESULTS: It was confirmed that five commonly used chemotherapy drugs had no cytotoxic activity in BE (2)-c cells. Six of 12 ozonides tested were active in-vitro at concentrations achievable in vivo with OZ513 being most active (IC50 = 0.5 mcg/ml). OZ513 activity was confirmed in IMR-32 and A673 cells. The Ao peak on cell-cycle analysis was increased after treatment with OZ513 in a concentration dependent fashion which when coupled with results from western blot analysis which showed an increase in cleaved capase-3 and cleaved PARP supported an increase in apoptosis. There was a concentration dependent decline in the MYCN and a cyclinD1 protein indicative of anti-proliferative activity and cell cycle disruption. OXPHOS metabolism was unaffected by OZ513 treatment while glycolysis was increased. There was a significant delay in time to tumor development in mice treated with OZ513 and a decline in the rate of tumor growth. CONCLUSIONS: The antimalarial ozonide OZ513 has effective in-vitro and in-vivo activity against a pleiotropic drug resistant neuroblastoma cell-line. Treatment with OZ513 increased apoptotic markers and glycolysis with a decline in the MYCN oncogene and the cell cycle regulator cyclinD1. These effects suggest adaptation to cellular stress by mechanism which remain unclear. More... »

PAGES

867

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s12885-016-2872-2

DOI

http://dx.doi.org/10.1186/s12885-016-2872-2

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1043961647

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27821095


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": "Antimalarials", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Antineoplastic Agents", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Apoptosis", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Artemisinins", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Biomarkers", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Caspase 3", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Cell Cycle", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Cell Line, Tumor", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Disease Models, Animal", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Drug Resistance, Neoplasm", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Heterocyclic Compounds", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Humans", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Metabolome", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Metabolomics", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Mice", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Neuroblastoma", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Xenograft Model Antitumor Assays", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "University of Nebraska Medical Center", 
          "id": "https://www.grid.ac/institutes/grid.266813.8", 
          "name": [
            "College of Medicine, Division of Pediatrics, University of Nebraska Medical Center, Omaha, NE, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Coulter", 
        "givenName": "Don W.", 
        "id": "sg:person.01130624227.89", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01130624227.89"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Nebraska Medical Center", 
          "id": "https://www.grid.ac/institutes/grid.266813.8", 
          "name": [
            "Department of Pharmacy Practice and Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "McGuire", 
        "givenName": "Timothy R.", 
        "id": "sg:person.0705231250.86", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0705231250.86"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Nebraska Medical Center", 
          "id": "https://www.grid.ac/institutes/grid.266813.8", 
          "name": [
            "Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Sharp", 
        "givenName": "John G.", 
        "id": "sg:person.013023463232.19", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013023463232.19"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Nebraska Medical Center", 
          "id": "https://www.grid.ac/institutes/grid.266813.8", 
          "name": [
            "Department of Pharmacy Practice and Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "McIntyre", 
        "givenName": "Erin M.", 
        "id": "sg:person.01245052627.66", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01245052627.66"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Nebraska Medical Center", 
          "id": "https://www.grid.ac/institutes/grid.266813.8", 
          "name": [
            "Department of Pharmacy Practice and Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Dong", 
        "givenName": "Yuxiang", 
        "id": "sg:person.01264602676.08", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01264602676.08"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Nebraska Medical Center", 
          "id": "https://www.grid.ac/institutes/grid.266813.8", 
          "name": [
            "Department of Pharmacy Practice and Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Wang", 
        "givenName": "Xiaofang", 
        "id": "sg:person.01046175313.93", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01046175313.93"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Nebraska Medical Center", 
          "id": "https://www.grid.ac/institutes/grid.266813.8", 
          "name": [
            "Department of Pharmacy Practice and Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Gray", 
        "givenName": "Shawn", 
        "id": "sg:person.013630535065.89", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013630535065.89"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Nebraska Medical Center", 
          "id": "https://www.grid.ac/institutes/grid.266813.8", 
          "name": [
            "Department of Pharmacy Practice and Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Alexander", 
        "givenName": "Gracey R.", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Nebraska Medical Center", 
          "id": "https://www.grid.ac/institutes/grid.266813.8", 
          "name": [
            "College of Medicine, Division of Pediatrics, University of Nebraska Medical Center, Omaha, NE, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Chatuverdi", 
        "givenName": "Nagendra K.", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Nebraska Medical Center", 
          "id": "https://www.grid.ac/institutes/grid.266813.8", 
          "name": [
            "Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Joshi", 
        "givenName": "Shantaram S.", 
        "id": "sg:person.07355130657.98", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.07355130657.98"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Nebraska Medical Center", 
          "id": "https://www.grid.ac/institutes/grid.266813.8", 
          "name": [
            "Department of Pharmacy Practice and Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Chen", 
        "givenName": "Xiaoyu", 
        "id": "sg:person.016616437065.43", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016616437065.43"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Nebraska Medical Center", 
          "id": "https://www.grid.ac/institutes/grid.266813.8", 
          "name": [
            "Department of Pharmacy Practice and Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Vennerstrom", 
        "givenName": "Jonathan L.", 
        "id": "sg:person.01056254747.41", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01056254747.41"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "https://doi.org/10.18632/oncotarget.7714", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1001460120"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.3109/00498254.2012.713530", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1004321499"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1172/jci69741", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1004645926"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.3322/caac.21219", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1011762576"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1073/pnas.1015762108", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1013241775"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1111/j.1365-2125.2012.04368.x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1013702742"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/s40170-015-0130-8", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1016220143", 
          "https://doi.org/10.1186/s40170-015-0130-8"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/s40170-015-0130-8", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1016220143", 
          "https://doi.org/10.1186/s40170-015-0130-8"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/0008-5472.can-10-0740", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1017443824"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/0-306-46872-7_2", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1019559995", 
          "https://doi.org/10.1007/0-306-46872-7_2"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.bmt.1705809", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1023536051", 
          "https://doi.org/10.1038/sj.bmt.1705809"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/14651858.cd010685.pub2", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1024757082"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1371/journal.pone.0082962", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1025146004"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/aac.01033-07", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1025909460"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s1473-3099(15)00343-6", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1026034984"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.4103/2141-9248.153609", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1027724299"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1371/journal.pone.0007472", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1028520469"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1155/2012/247597", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1030690857"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1056/nejmoa0911123", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1031306714"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature02779", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1033258838", 
          "https://doi.org/10.1038/nature02779"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature02779", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1033258838", 
          "https://doi.org/10.1038/nature02779"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.bmcl.2006.12.007", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1034411225"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1056/nejmra0804577", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1034486634"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1080/15384047.2015.1070987", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1038300722"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.bcp.2009.08.013", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1039215469"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1089/ars.2011.4243", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1039855435"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/0008-5472.can-14-3817", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1040337987"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1124/mol.64.2.382", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1040699455"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1074/jbc.m410450200", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1041201207"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1124/jpet.112.199216", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1041283626"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1073/pnas.1222404110", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1043760822"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ncomms10111", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1045601085", 
          "https://doi.org/10.1038/ncomms10111"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1371/journal.pone.0062771", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1045843419"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.onc.1209608", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1046914764", 
          "https://doi.org/10.1038/sj.onc.1209608"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.onc.1209608", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1046914764", 
          "https://doi.org/10.1038/sj.onc.1209608"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.4155/fmc.12.190", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1047502034"
        ], 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2016-12", 
    "datePublishedReg": "2016-12-01", 
    "description": "BACKGROUND: Evaluate the anti-tumor activity of ozonide antimalarials using a chemoresistant neuroblastoma cell line, BE (2)-c.\nMETHODS: The activity of 12 ozonides, artemisinin, and two semisynthetic artemisinins were tested for activity against two neuroblastoma cell-lines (BE (2)-c and IMR-32) and the Ewing's Sarcoma cell line A673 in an MTT viability assay. Time course data indicated that peak effect was seen 18\u00a0h after the start of treatment thus 18\u00a0h pre-treatment was used for all subsequent experiments. The most active ozonide (OZ513) was assessed in a propidium iodide cell cycle flow cytometry analysis which measured cell cycle transit and apoptosis. Metabolic effects of OZ513 in BE (2)-c cells was evaluated. Western blots for the apoptotic proteins cleaved capase-3 and cleaved PARP, the highly amplified oncogene MYCN, and the cell cycle regulator CyclinD1, were performed. These in-vitro experiments were followed by an in-vivo experiment in which NOD-scid gamma immunodeficient mice were injected subcutaneously with 1\u2009\u00d7\u2009106 BE (2)-c cells followed by immediate treatment with 50-100\u00a0mg/kg/day doses of OZ513 administered IP three times per week out to 23\u00a0days after injection of tumor. Incidence of tumor development, time to tumor development, and rate of tumor growth were assessed in DMSO treated controls (N\u2009=\u20096), and OZ513 treated mice (N\u2009=\u20095).\nRESULTS: It was confirmed that five commonly used chemotherapy drugs had no cytotoxic activity in BE (2)-c cells. Six of 12 ozonides tested were active in-vitro at concentrations achievable in vivo with OZ513 being most active (IC50\u2009=\u20090.5 mcg/ml). OZ513 activity was confirmed in IMR-32 and A673 cells. The Ao peak on cell-cycle analysis was increased after treatment with OZ513 in a concentration dependent fashion which when coupled with results from western blot analysis which showed an increase in cleaved capase-3 and cleaved PARP supported an increase in apoptosis. There was a concentration dependent decline in the MYCN and a cyclinD1 protein indicative of anti-proliferative activity and cell cycle disruption. OXPHOS metabolism was unaffected by OZ513 treatment while glycolysis was increased. There was a significant delay in time to tumor development in mice treated with OZ513 and a decline in the rate of tumor growth.\nCONCLUSIONS: The antimalarial ozonide OZ513 has effective in-vitro and in-vivo activity against a pleiotropic drug resistant neuroblastoma cell-line. Treatment with OZ513 increased apoptotic markers and glycolysis with a decline in the MYCN oncogene and the cell cycle regulator cyclinD1. These effects suggest adaptation to cellular stress by mechanism which remain unclear.", 
    "genre": "research_article", 
    "id": "sg:pub.10.1186/s12885-016-2872-2", 
    "inLanguage": [
      "en"
    ], 
    "isAccessibleForFree": true, 
    "isFundedItemOf": [
      {
        "id": "sg:grant.2439225", 
        "type": "MonetaryGrant"
      }
    ], 
    "isPartOf": [
      {
        "id": "sg:journal.1024632", 
        "issn": [
          "1471-2407"
        ], 
        "name": "BMC Cancer", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "1", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "16"
      }
    ], 
    "name": "Treatment of a chemoresistant neuroblastoma cell line with the antimalarial ozonide OZ513", 
    "pagination": "867", 
    "productId": [
      {
        "name": "readcube_id", 
        "type": "PropertyValue", 
        "value": [
          "d16791e27286e7d5eb88014e959058c8765383d72bde26f06cb50c7fd2225419"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "27821095"
        ]
      }, 
      {
        "name": "nlm_unique_id", 
        "type": "PropertyValue", 
        "value": [
          "100967800"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1186/s12885-016-2872-2"
        ]
      }, 
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1043961647"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1186/s12885-016-2872-2", 
      "https://app.dimensions.ai/details/publication/pub.1043961647"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2019-04-11T12:41", 
    "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/v90/0000000363_0000000363/records_70056_00000001.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://link.springer.com/10.1186%2Fs12885-016-2872-2"
  }
]
 

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

HOW TO GET THIS DATA PROGRAMMATICALLY:

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

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1186/s12885-016-2872-2'

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

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1186/s12885-016-2872-2'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1186/s12885-016-2872-2'

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

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1186/s12885-016-2872-2'


 

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

324 TRIPLES      21 PREDICATES      80 URIs      39 LITERALS      27 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1186/s12885-016-2872-2 schema:about N01007a1545bb47318065d90e8a9ea002
2 N087b7895282348158c7d435b3526efda
3 N1c485dfb57944a379cd5f44e99ae4536
4 N1cf7fa9a34594d998094c3370405860b
5 N23bf83f1739a4f20a3544c71d6f11644
6 N4714c3f158e345e8ae8db35355f3e663
7 N5b632c6ccee844308bd992f0763d7d2d
8 N637e1a538970420ba1919edbe923aac6
9 N871f3a8e43624f689b25407d5ec306ea
10 N89604712c75f4dc4b94357f2844cffa6
11 N8e59051c55a642cc8a0198952810207f
12 N9655a1cb8e1f4b77be4afb39b9b76e42
13 N9ee60ceef83c43e7a6acb5e3612ee4e4
14 Na95133e3a7924a3098c8ac21bee9256a
15 Nbb253bdd541f4baca191610a886b7a7f
16 Nbb467e8aed244affabd52b775b7089ff
17 Nbd79fcf6fc544e579153655d8ebb82d4
18 Nfde5106904dd4abea0a293012e94a2c1
19 anzsrc-for:11
20 anzsrc-for:1112
21 schema:author N48cd7434740140318863b45d17d4a134
22 schema:citation sg:pub.10.1007/0-306-46872-7_2
23 sg:pub.10.1038/nature02779
24 sg:pub.10.1038/ncomms10111
25 sg:pub.10.1038/sj.bmt.1705809
26 sg:pub.10.1038/sj.onc.1209608
27 sg:pub.10.1186/s40170-015-0130-8
28 https://doi.org/10.1002/14651858.cd010685.pub2
29 https://doi.org/10.1016/j.bcp.2009.08.013
30 https://doi.org/10.1016/j.bmcl.2006.12.007
31 https://doi.org/10.1016/s1473-3099(15)00343-6
32 https://doi.org/10.1056/nejmoa0911123
33 https://doi.org/10.1056/nejmra0804577
34 https://doi.org/10.1073/pnas.1015762108
35 https://doi.org/10.1073/pnas.1222404110
36 https://doi.org/10.1074/jbc.m410450200
37 https://doi.org/10.1080/15384047.2015.1070987
38 https://doi.org/10.1089/ars.2011.4243
39 https://doi.org/10.1111/j.1365-2125.2012.04368.x
40 https://doi.org/10.1124/jpet.112.199216
41 https://doi.org/10.1124/mol.64.2.382
42 https://doi.org/10.1128/aac.01033-07
43 https://doi.org/10.1155/2012/247597
44 https://doi.org/10.1158/0008-5472.can-10-0740
45 https://doi.org/10.1158/0008-5472.can-14-3817
46 https://doi.org/10.1172/jci69741
47 https://doi.org/10.1371/journal.pone.0007472
48 https://doi.org/10.1371/journal.pone.0062771
49 https://doi.org/10.1371/journal.pone.0082962
50 https://doi.org/10.18632/oncotarget.7714
51 https://doi.org/10.3109/00498254.2012.713530
52 https://doi.org/10.3322/caac.21219
53 https://doi.org/10.4103/2141-9248.153609
54 https://doi.org/10.4155/fmc.12.190
55 schema:datePublished 2016-12
56 schema:datePublishedReg 2016-12-01
57 schema:description BACKGROUND: Evaluate the anti-tumor activity of ozonide antimalarials using a chemoresistant neuroblastoma cell line, BE (2)-c. METHODS: The activity of 12 ozonides, artemisinin, and two semisynthetic artemisinins were tested for activity against two neuroblastoma cell-lines (BE (2)-c and IMR-32) and the Ewing's Sarcoma cell line A673 in an MTT viability assay. Time course data indicated that peak effect was seen 18 h after the start of treatment thus 18 h pre-treatment was used for all subsequent experiments. The most active ozonide (OZ513) was assessed in a propidium iodide cell cycle flow cytometry analysis which measured cell cycle transit and apoptosis. Metabolic effects of OZ513 in BE (2)-c cells was evaluated. Western blots for the apoptotic proteins cleaved capase-3 and cleaved PARP, the highly amplified oncogene MYCN, and the cell cycle regulator CyclinD1, were performed. These in-vitro experiments were followed by an in-vivo experiment in which NOD-scid gamma immunodeficient mice were injected subcutaneously with 1 × 106 BE (2)-c cells followed by immediate treatment with 50-100 mg/kg/day doses of OZ513 administered IP three times per week out to 23 days after injection of tumor. Incidence of tumor development, time to tumor development, and rate of tumor growth were assessed in DMSO treated controls (N = 6), and OZ513 treated mice (N = 5). RESULTS: It was confirmed that five commonly used chemotherapy drugs had no cytotoxic activity in BE (2)-c cells. Six of 12 ozonides tested were active in-vitro at concentrations achievable in vivo with OZ513 being most active (IC50 = 0.5 mcg/ml). OZ513 activity was confirmed in IMR-32 and A673 cells. The Ao peak on cell-cycle analysis was increased after treatment with OZ513 in a concentration dependent fashion which when coupled with results from western blot analysis which showed an increase in cleaved capase-3 and cleaved PARP supported an increase in apoptosis. There was a concentration dependent decline in the MYCN and a cyclinD1 protein indicative of anti-proliferative activity and cell cycle disruption. OXPHOS metabolism was unaffected by OZ513 treatment while glycolysis was increased. There was a significant delay in time to tumor development in mice treated with OZ513 and a decline in the rate of tumor growth. CONCLUSIONS: The antimalarial ozonide OZ513 has effective in-vitro and in-vivo activity against a pleiotropic drug resistant neuroblastoma cell-line. Treatment with OZ513 increased apoptotic markers and glycolysis with a decline in the MYCN oncogene and the cell cycle regulator cyclinD1. These effects suggest adaptation to cellular stress by mechanism which remain unclear.
58 schema:genre research_article
59 schema:inLanguage en
60 schema:isAccessibleForFree true
61 schema:isPartOf N08f39b7a5c37477aa84d18a1868e21de
62 Ne43029e2dba044ed8db30ed312e240bd
63 sg:journal.1024632
64 schema:name Treatment of a chemoresistant neuroblastoma cell line with the antimalarial ozonide OZ513
65 schema:pagination 867
66 schema:productId N135a6cafb9d34467b27ba1b37fb9ea07
67 N4c381d59998e4c37835c365698577b2f
68 N856380ea2d3541fe9ce10e96f40a1deb
69 Nf3b4961a62c34dea842214a2db92d028
70 Nf94f0e3309be4360a9ec811d83a66d93
71 schema:sameAs https://app.dimensions.ai/details/publication/pub.1043961647
72 https://doi.org/10.1186/s12885-016-2872-2
73 schema:sdDatePublished 2019-04-11T12:41
74 schema:sdLicense https://scigraph.springernature.com/explorer/license/
75 schema:sdPublisher N12ec56d3efa34b4e997970621b59d00d
76 schema:url https://link.springer.com/10.1186%2Fs12885-016-2872-2
77 sgo:license sg:explorer/license/
78 sgo:sdDataset articles
79 rdf:type schema:ScholarlyArticle
80 N01007a1545bb47318065d90e8a9ea002 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
81 schema:name Neuroblastoma
82 rdf:type schema:DefinedTerm
83 N087b7895282348158c7d435b3526efda schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
84 schema:name Antineoplastic Agents
85 rdf:type schema:DefinedTerm
86 N08f39b7a5c37477aa84d18a1868e21de schema:volumeNumber 16
87 rdf:type schema:PublicationVolume
88 N092bc420ff514e86978e3f0624fc72de rdf:first sg:person.013630535065.89
89 rdf:rest Ne13acffb156f457992513e9f44bd9823
90 N0f930d7bd32d450999bfe79c9deb508b rdf:first sg:person.01046175313.93
91 rdf:rest N092bc420ff514e86978e3f0624fc72de
92 N12ec56d3efa34b4e997970621b59d00d schema:name Springer Nature - SN SciGraph project
93 rdf:type schema:Organization
94 N135a6cafb9d34467b27ba1b37fb9ea07 schema:name doi
95 schema:value 10.1186/s12885-016-2872-2
96 rdf:type schema:PropertyValue
97 N1c485dfb57944a379cd5f44e99ae4536 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
98 schema:name Animals
99 rdf:type schema:DefinedTerm
100 N1cf7fa9a34594d998094c3370405860b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
101 schema:name Antimalarials
102 rdf:type schema:DefinedTerm
103 N23bf83f1739a4f20a3544c71d6f11644 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
104 schema:name Artemisinins
105 rdf:type schema:DefinedTerm
106 N338109528aaa4c6e867c49fe221d3a26 rdf:first sg:person.013023463232.19
107 rdf:rest Nc6c2f406101e4f8395f5823e001f6428
108 N37f84b1199304890a160095e8a4de44f schema:affiliation https://www.grid.ac/institutes/grid.266813.8
109 schema:familyName Chatuverdi
110 schema:givenName Nagendra K.
111 rdf:type schema:Person
112 N470de77772294ce0a0d6a683bdb37db3 rdf:first sg:person.01264602676.08
113 rdf:rest N0f930d7bd32d450999bfe79c9deb508b
114 N4714c3f158e345e8ae8db35355f3e663 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
115 schema:name Cell Cycle
116 rdf:type schema:DefinedTerm
117 N48cd7434740140318863b45d17d4a134 rdf:first sg:person.01130624227.89
118 rdf:rest Nefb6da7fec7d4d0ab1fe6c9377db30fc
119 N4c381d59998e4c37835c365698577b2f schema:name pubmed_id
120 schema:value 27821095
121 rdf:type schema:PropertyValue
122 N5b632c6ccee844308bd992f0763d7d2d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
123 schema:name Disease Models, Animal
124 rdf:type schema:DefinedTerm
125 N637e1a538970420ba1919edbe923aac6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
126 schema:name Xenograft Model Antitumor Assays
127 rdf:type schema:DefinedTerm
128 N7877fba127b04114aaa3409291c973cd rdf:first sg:person.016616437065.43
129 rdf:rest Nad5717e9086f43329261ea6e9f225a9a
130 N856380ea2d3541fe9ce10e96f40a1deb schema:name nlm_unique_id
131 schema:value 100967800
132 rdf:type schema:PropertyValue
133 N871f3a8e43624f689b25407d5ec306ea schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
134 schema:name Metabolomics
135 rdf:type schema:DefinedTerm
136 N89604712c75f4dc4b94357f2844cffa6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
137 schema:name Biomarkers
138 rdf:type schema:DefinedTerm
139 N8e59051c55a642cc8a0198952810207f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
140 schema:name Metabolome
141 rdf:type schema:DefinedTerm
142 N9655a1cb8e1f4b77be4afb39b9b76e42 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
143 schema:name Heterocyclic Compounds
144 rdf:type schema:DefinedTerm
145 N9ee60ceef83c43e7a6acb5e3612ee4e4 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
146 schema:name Caspase 3
147 rdf:type schema:DefinedTerm
148 Na95133e3a7924a3098c8ac21bee9256a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
149 schema:name Mice
150 rdf:type schema:DefinedTerm
151 Nad5717e9086f43329261ea6e9f225a9a rdf:first sg:person.01056254747.41
152 rdf:rest rdf:nil
153 Nbb253bdd541f4baca191610a886b7a7f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
154 schema:name Drug Resistance, Neoplasm
155 rdf:type schema:DefinedTerm
156 Nbb467e8aed244affabd52b775b7089ff schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
157 schema:name Apoptosis
158 rdf:type schema:DefinedTerm
159 Nbd13198018564b2ca55d990489f64d62 rdf:first sg:person.07355130657.98
160 rdf:rest N7877fba127b04114aaa3409291c973cd
161 Nbd79fcf6fc544e579153655d8ebb82d4 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
162 schema:name Cell Line, Tumor
163 rdf:type schema:DefinedTerm
164 Nc6c2f406101e4f8395f5823e001f6428 rdf:first sg:person.01245052627.66
165 rdf:rest N470de77772294ce0a0d6a683bdb37db3
166 Ncd1e5904df3743c5a3e4392b92972b60 schema:affiliation https://www.grid.ac/institutes/grid.266813.8
167 schema:familyName Alexander
168 schema:givenName Gracey R.
169 rdf:type schema:Person
170 Nd9c7d6a394bc496b9c67b4bee9c9161f rdf:first N37f84b1199304890a160095e8a4de44f
171 rdf:rest Nbd13198018564b2ca55d990489f64d62
172 Ne13acffb156f457992513e9f44bd9823 rdf:first Ncd1e5904df3743c5a3e4392b92972b60
173 rdf:rest Nd9c7d6a394bc496b9c67b4bee9c9161f
174 Ne43029e2dba044ed8db30ed312e240bd schema:issueNumber 1
175 rdf:type schema:PublicationIssue
176 Nefb6da7fec7d4d0ab1fe6c9377db30fc rdf:first sg:person.0705231250.86
177 rdf:rest N338109528aaa4c6e867c49fe221d3a26
178 Nf3b4961a62c34dea842214a2db92d028 schema:name dimensions_id
179 schema:value pub.1043961647
180 rdf:type schema:PropertyValue
181 Nf94f0e3309be4360a9ec811d83a66d93 schema:name readcube_id
182 schema:value d16791e27286e7d5eb88014e959058c8765383d72bde26f06cb50c7fd2225419
183 rdf:type schema:PropertyValue
184 Nfde5106904dd4abea0a293012e94a2c1 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
185 schema:name Humans
186 rdf:type schema:DefinedTerm
187 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
188 schema:name Medical and Health Sciences
189 rdf:type schema:DefinedTerm
190 anzsrc-for:1112 schema:inDefinedTermSet anzsrc-for:
191 schema:name Oncology and Carcinogenesis
192 rdf:type schema:DefinedTerm
193 sg:grant.2439225 http://pending.schema.org/fundedItem sg:pub.10.1186/s12885-016-2872-2
194 rdf:type schema:MonetaryGrant
195 sg:journal.1024632 schema:issn 1471-2407
196 schema:name BMC Cancer
197 rdf:type schema:Periodical
198 sg:person.01046175313.93 schema:affiliation https://www.grid.ac/institutes/grid.266813.8
199 schema:familyName Wang
200 schema:givenName Xiaofang
201 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01046175313.93
202 rdf:type schema:Person
203 sg:person.01056254747.41 schema:affiliation https://www.grid.ac/institutes/grid.266813.8
204 schema:familyName Vennerstrom
205 schema:givenName Jonathan L.
206 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01056254747.41
207 rdf:type schema:Person
208 sg:person.01130624227.89 schema:affiliation https://www.grid.ac/institutes/grid.266813.8
209 schema:familyName Coulter
210 schema:givenName Don W.
211 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01130624227.89
212 rdf:type schema:Person
213 sg:person.01245052627.66 schema:affiliation https://www.grid.ac/institutes/grid.266813.8
214 schema:familyName McIntyre
215 schema:givenName Erin M.
216 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01245052627.66
217 rdf:type schema:Person
218 sg:person.01264602676.08 schema:affiliation https://www.grid.ac/institutes/grid.266813.8
219 schema:familyName Dong
220 schema:givenName Yuxiang
221 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01264602676.08
222 rdf:type schema:Person
223 sg:person.013023463232.19 schema:affiliation https://www.grid.ac/institutes/grid.266813.8
224 schema:familyName Sharp
225 schema:givenName John G.
226 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013023463232.19
227 rdf:type schema:Person
228 sg:person.013630535065.89 schema:affiliation https://www.grid.ac/institutes/grid.266813.8
229 schema:familyName Gray
230 schema:givenName Shawn
231 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013630535065.89
232 rdf:type schema:Person
233 sg:person.016616437065.43 schema:affiliation https://www.grid.ac/institutes/grid.266813.8
234 schema:familyName Chen
235 schema:givenName Xiaoyu
236 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016616437065.43
237 rdf:type schema:Person
238 sg:person.0705231250.86 schema:affiliation https://www.grid.ac/institutes/grid.266813.8
239 schema:familyName McGuire
240 schema:givenName Timothy R.
241 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0705231250.86
242 rdf:type schema:Person
243 sg:person.07355130657.98 schema:affiliation https://www.grid.ac/institutes/grid.266813.8
244 schema:familyName Joshi
245 schema:givenName Shantaram S.
246 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.07355130657.98
247 rdf:type schema:Person
248 sg:pub.10.1007/0-306-46872-7_2 schema:sameAs https://app.dimensions.ai/details/publication/pub.1019559995
249 https://doi.org/10.1007/0-306-46872-7_2
250 rdf:type schema:CreativeWork
251 sg:pub.10.1038/nature02779 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033258838
252 https://doi.org/10.1038/nature02779
253 rdf:type schema:CreativeWork
254 sg:pub.10.1038/ncomms10111 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045601085
255 https://doi.org/10.1038/ncomms10111
256 rdf:type schema:CreativeWork
257 sg:pub.10.1038/sj.bmt.1705809 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023536051
258 https://doi.org/10.1038/sj.bmt.1705809
259 rdf:type schema:CreativeWork
260 sg:pub.10.1038/sj.onc.1209608 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046914764
261 https://doi.org/10.1038/sj.onc.1209608
262 rdf:type schema:CreativeWork
263 sg:pub.10.1186/s40170-015-0130-8 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016220143
264 https://doi.org/10.1186/s40170-015-0130-8
265 rdf:type schema:CreativeWork
266 https://doi.org/10.1002/14651858.cd010685.pub2 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024757082
267 rdf:type schema:CreativeWork
268 https://doi.org/10.1016/j.bcp.2009.08.013 schema:sameAs https://app.dimensions.ai/details/publication/pub.1039215469
269 rdf:type schema:CreativeWork
270 https://doi.org/10.1016/j.bmcl.2006.12.007 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034411225
271 rdf:type schema:CreativeWork
272 https://doi.org/10.1016/s1473-3099(15)00343-6 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026034984
273 rdf:type schema:CreativeWork
274 https://doi.org/10.1056/nejmoa0911123 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031306714
275 rdf:type schema:CreativeWork
276 https://doi.org/10.1056/nejmra0804577 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034486634
277 rdf:type schema:CreativeWork
278 https://doi.org/10.1073/pnas.1015762108 schema:sameAs https://app.dimensions.ai/details/publication/pub.1013241775
279 rdf:type schema:CreativeWork
280 https://doi.org/10.1073/pnas.1222404110 schema:sameAs https://app.dimensions.ai/details/publication/pub.1043760822
281 rdf:type schema:CreativeWork
282 https://doi.org/10.1074/jbc.m410450200 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041201207
283 rdf:type schema:CreativeWork
284 https://doi.org/10.1080/15384047.2015.1070987 schema:sameAs https://app.dimensions.ai/details/publication/pub.1038300722
285 rdf:type schema:CreativeWork
286 https://doi.org/10.1089/ars.2011.4243 schema:sameAs https://app.dimensions.ai/details/publication/pub.1039855435
287 rdf:type schema:CreativeWork
288 https://doi.org/10.1111/j.1365-2125.2012.04368.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1013702742
289 rdf:type schema:CreativeWork
290 https://doi.org/10.1124/jpet.112.199216 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041283626
291 rdf:type schema:CreativeWork
292 https://doi.org/10.1124/mol.64.2.382 schema:sameAs https://app.dimensions.ai/details/publication/pub.1040699455
293 rdf:type schema:CreativeWork
294 https://doi.org/10.1128/aac.01033-07 schema:sameAs https://app.dimensions.ai/details/publication/pub.1025909460
295 rdf:type schema:CreativeWork
296 https://doi.org/10.1155/2012/247597 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030690857
297 rdf:type schema:CreativeWork
298 https://doi.org/10.1158/0008-5472.can-10-0740 schema:sameAs https://app.dimensions.ai/details/publication/pub.1017443824
299 rdf:type schema:CreativeWork
300 https://doi.org/10.1158/0008-5472.can-14-3817 schema:sameAs https://app.dimensions.ai/details/publication/pub.1040337987
301 rdf:type schema:CreativeWork
302 https://doi.org/10.1172/jci69741 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004645926
303 rdf:type schema:CreativeWork
304 https://doi.org/10.1371/journal.pone.0007472 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028520469
305 rdf:type schema:CreativeWork
306 https://doi.org/10.1371/journal.pone.0062771 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045843419
307 rdf:type schema:CreativeWork
308 https://doi.org/10.1371/journal.pone.0082962 schema:sameAs https://app.dimensions.ai/details/publication/pub.1025146004
309 rdf:type schema:CreativeWork
310 https://doi.org/10.18632/oncotarget.7714 schema:sameAs https://app.dimensions.ai/details/publication/pub.1001460120
311 rdf:type schema:CreativeWork
312 https://doi.org/10.3109/00498254.2012.713530 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004321499
313 rdf:type schema:CreativeWork
314 https://doi.org/10.3322/caac.21219 schema:sameAs https://app.dimensions.ai/details/publication/pub.1011762576
315 rdf:type schema:CreativeWork
316 https://doi.org/10.4103/2141-9248.153609 schema:sameAs https://app.dimensions.ai/details/publication/pub.1027724299
317 rdf:type schema:CreativeWork
318 https://doi.org/10.4155/fmc.12.190 schema:sameAs https://app.dimensions.ai/details/publication/pub.1047502034
319 rdf:type schema:CreativeWork
320 https://www.grid.ac/institutes/grid.266813.8 schema:alternateName University of Nebraska Medical Center
321 schema:name College of Medicine, Division of Pediatrics, University of Nebraska Medical Center, Omaha, NE, USA
322 Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE, USA
323 Department of Pharmacy Practice and Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA
324 rdf:type schema:Organization
 




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


...