Synergistic induction of tumor cell apoptosis by death receptor antibody and chemotherapy agent through JNK/p38 and mitochondrial death pathway View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2003-04-03

AUTHORS

Toshiaki Ohtsuka, Donald Buchsbaum, Patsy Oliver, Sharmila Makhija, Robert Kimberly, Tong Zhou

ABSTRACT

Using two agonistic monoclonal antibodies specific for each death receptor of TRAIL, 2E12 (anti-human DR4) and TRA-8 (anti-human DR5), we examined the signal transduction of the death receptors in combination with or without Q1chemotherapy agents such as Adriamycin (doxorubicin hydrochloride) and Cisplatin. Our results demonstrated that chemotherapy agents were able to enhance apoptosis-inducing activity of these antibodies against several different types of tumor cell lines through enhanced caspase activation. The combination of the antibodies and chemotherapy agents led to a synergistical activation of the JNK/p38 MAP kinase, which was mediated by MKK4. The combination also caused an increased release of cytochrome c and Smac/DIABLO from mitochondria in parallel with the profound loss of mitochondrial membrane potential. These results suggest that the enhanced activation of the JNK/p38 kinase and the mitochondrial apoptosis pathways play a crucial role in synergistic induction of the death receptor-mediated apoptosis by chemotherapy agents. Thus, the simultaneous targeting of cell surface death receptors with agonistic antibodies and the intracellular JNK/p38 and the mitochondrial death pathways with chemotherapy agents would enhance the efficacy and selectivity of both agents in cancer therapy. More... »

PAGES

2034-2044

Journal

TITLE

Oncogene

ISSUE

13

VOLUME

22

Related Patents

  • Pharmaceutical Compositions Containing Sc(Fv)2
  • Ligand Having Agonistic Activity To Mutated Receptor
  • Degraded Tpo Agonist Antibody
  • Antibody Selective For A Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Receptor And Uses Thereof
  • Agents And Methods Related To Screening For Resistance To Dr5 And Reducing Resistance To Dr5 Agonists
  • Treating Basal-Like Genotype Cancers
  • Antibody Selective For A Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Receptor And Uses Thereof
  • Structural Isomers Of Sc(Fv)2
  • Antibody Selective For A Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Receptor And Uses Thereof
  • Anti-Mpl Antibodies
  • Combinations Of Antibodies Selective For Dr5 And Other Therapeutic Agents
  • Agents And Methods Related To Reducing Resistance To Apoptosis-Inducing Death Receptor Agonists
  • Treating Basal-Like Genotype Cancers
  • Targeting Cancer Stem Cells With Dr5 Agonists
  • Polypeptide Inducing Apoptosis
  • Pharmaceutical Compositions Containing Sc(Fv)2
  • Degraded Tpo Agonist Antibody
  • Agents And Methods Related To Reducing Resistance To Apoptosis-Inducing Death Receptor Agonists
  • Anti-Mpl Antibodies
  • Antibody Selective For A Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Receptor Dr5 And Uses Thereof
  • Directed Differentiation Of Stem Cells
  • Cell Death-Inducing Agent
  • Antibody Selective For A Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Receptor And Uses Thereof
  • Antibody Specifically Binding To Dr5 And Composition For Preventing Or Treating Cancers Comprising The Same
  • Combinations Of Antibodies Selective For Dr5 And Other Therapeutic Agents
  • Antibody Selective For Dr4 And Uses Thereof
  • Stabilizer For Protein Preparation Comprising Meglumine And Use Thereof
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/sj.onc.1206290

    DOI

    http://dx.doi.org/10.1038/sj.onc.1206290

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1047996205

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/12673208


    Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
    Incoming Citations Browse incoming citations for this publication using opencitations.net

    JSON-LD is the canonical representation for SciGraph data.

    TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

    [
      {
        "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
        "about": [
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Medical and Health Sciences", 
            "type": "DefinedTerm"
          }, 
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1103", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Clinical Sciences", 
            "type": "DefinedTerm"
          }, 
          {
            "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"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Acetylcysteine", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Adenocarcinoma", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Antibodies, Monoclonal", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Antibody Specificity", 
            "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": "Apoptosis Regulatory Proteins", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Breast Neoplasms", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Carrier Proteins", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Caspases", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cisplatin", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cytochrome c Group", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "DNA Fragmentation", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Doxorubicin", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Drug Synergism", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Enzyme Activation", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Enzyme Inhibitors", 
            "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": "Intracellular Membranes", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Intracellular Signaling Peptides and Proteins", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "JNK Mitogen-Activated Protein Kinases", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "MAP Kinase Kinase 4", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "MAP Kinase Signaling System", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Membrane Potentials", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Mitochondria", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Mitochondrial Proteins", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Mitogen-Activated Protein Kinase Kinases", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Mitogen-Activated Protein Kinases", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Paclitaxel", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Receptors, TNF-Related Apoptosis-Inducing Ligand", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Receptors, Tumor Necrosis Factor", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Tumor Cells, Cultured", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "p38 Mitogen-Activated Protein Kinases", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "alternateName": "Biomedical Research Laboratories, Sankyo Co., Ltd, 140\u20138710, Tokyo, Japan", 
              "id": "http://www.grid.ac/institutes/grid.410844.d", 
              "name": [
                "Biomedical Research Laboratories, Sankyo Co., Ltd, 140\u20138710, Tokyo, Japan"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Ohtsuka", 
            "givenName": "Toshiaki", 
            "id": "sg:person.01217265717.13", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01217265717.13"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Radiation Biology, University of Alabama at Birmingham, 35294, Birmingham, AL, USA", 
              "id": "http://www.grid.ac/institutes/grid.265892.2", 
              "name": [
                "Department of Radiation Biology, University of Alabama at Birmingham, 35294, Birmingham, AL, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Buchsbaum", 
            "givenName": "Donald", 
            "id": "sg:person.01137705050.57", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01137705050.57"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Radiation Biology, University of Alabama at Birmingham, 35294, Birmingham, AL, USA", 
              "id": "http://www.grid.ac/institutes/grid.265892.2", 
              "name": [
                "Department of Radiation Biology, University of Alabama at Birmingham, 35294, Birmingham, AL, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Oliver", 
            "givenName": "Patsy", 
            "id": "sg:person.0725160173.26", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0725160173.26"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Division of Gynecologic Oncology, University of Alabama at Birmingham, 35294, Birmingham, AL, USA", 
              "id": "http://www.grid.ac/institutes/grid.265892.2", 
              "name": [
                "Division of Gynecologic Oncology, University of Alabama at Birmingham, 35294, Birmingham, AL, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Makhija", 
            "givenName": "Sharmila", 
            "id": "sg:person.0755422217.45", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0755422217.45"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Medicine, University of Alabama at Birmingham, 35294, Birmingham, AL, USA", 
              "id": "http://www.grid.ac/institutes/grid.265892.2", 
              "name": [
                "Department of Medicine, University of Alabama at Birmingham, 35294, Birmingham, AL, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Kimberly", 
            "givenName": "Robert", 
            "id": "sg:person.01304356355.83", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01304356355.83"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Medicine, University of Alabama at Birmingham, 35294, Birmingham, AL, USA", 
              "id": "http://www.grid.ac/institutes/grid.265892.2", 
              "name": [
                "Department of Medicine, University of Alabama at Birmingham, 35294, Birmingham, AL, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Zhou", 
            "givenName": "Tong", 
            "id": "sg:person.0664616100.38", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0664616100.38"
            ], 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "sg:pub.10.1038/35008667", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1012881410", 
              "https://doi.org/10.1038/35008667"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/74994", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1019830643", 
              "https://doi.org/10.1038/74994"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/5505", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1038229847", 
              "https://doi.org/10.1038/5505"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1023/a:1011336726649", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1006241578", 
              "https://doi.org/10.1023/a:1011336726649"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/5517", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1010598958", 
              "https://doi.org/10.1038/5517"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/4723", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1001523482", 
              "https://doi.org/10.1038/4723"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/91000", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1047281881", 
              "https://doi.org/10.1038/91000"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/75045", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1044338034", 
              "https://doi.org/10.1038/75045"
            ], 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "2003-04-03", 
        "datePublishedReg": "2003-04-03", 
        "description": "Using two agonistic monoclonal antibodies specific for each death receptor of TRAIL, 2E12 (anti-human DR4) and TRA-8 (anti-human DR5), we examined the signal transduction of the death receptors in combination with or without Q1chemotherapy agents such as Adriamycin (doxorubicin hydrochloride) and Cisplatin. Our results demonstrated that chemotherapy agents were able to enhance apoptosis-inducing activity of these antibodies against several different types of tumor cell lines through enhanced caspase activation. The combination of the antibodies and chemotherapy agents led to a synergistical activation of the JNK/p38 MAP kinase, which was mediated by MKK4. The combination also caused an increased release of cytochrome c and Smac/DIABLO from mitochondria in parallel with the profound loss of mitochondrial membrane potential. These results suggest that the enhanced activation of the JNK/p38 kinase and the mitochondrial apoptosis pathways play a crucial role in synergistic induction of the death receptor-mediated apoptosis by chemotherapy agents. Thus, the simultaneous targeting of cell surface death receptors with agonistic antibodies and the intracellular JNK/p38 and the mitochondrial death pathways with chemotherapy agents would enhance the efficacy and selectivity of both agents in cancer therapy.", 
        "genre": "article", 
        "id": "sg:pub.10.1038/sj.onc.1206290", 
        "inLanguage": "en", 
        "isAccessibleForFree": true, 
        "isFundedItemOf": [
          {
            "id": "sg:grant.2440147", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.2440161", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.2567549", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.7133716", 
            "type": "MonetaryGrant"
          }
        ], 
        "isPartOf": [
          {
            "id": "sg:journal.1097543", 
            "issn": [
              "0950-9232", 
              "1476-5594"
            ], 
            "name": "Oncogene", 
            "publisher": "Springer Nature", 
            "type": "Periodical"
          }, 
          {
            "issueNumber": "13", 
            "type": "PublicationIssue"
          }, 
          {
            "type": "PublicationVolume", 
            "volumeNumber": "22"
          }
        ], 
        "keywords": [
          "mitochondrial death pathway", 
          "JNK/p38", 
          "death receptors", 
          "death pathways", 
          "JNK/p38 kinases", 
          "JNK/p38 MAP kinase", 
          "cell surface death receptor", 
          "death receptor-mediated apoptosis", 
          "Smac/DIABLO", 
          "synergistic induction", 
          "surface death receptor", 
          "receptor-mediated apoptosis", 
          "mitochondrial apoptosis pathway", 
          "p38 MAP kinase", 
          "mitochondrial membrane potential", 
          "apoptosis-inducing activity", 
          "signal transduction", 
          "caspase activation", 
          "MAP kinase", 
          "p38 kinase", 
          "apoptosis pathway", 
          "cytochrome c", 
          "tumor cell apoptosis", 
          "tumor cell lines", 
          "agonistic monoclonal antibody", 
          "cell apoptosis", 
          "cell lines", 
          "membrane potential", 
          "kinase", 
          "pathway", 
          "p38", 
          "simultaneous targeting", 
          "enhanced activation", 
          "apoptosis", 
          "agonistic antibodies", 
          "activation", 
          "crucial role", 
          "cancer therapy", 
          "receptors", 
          "MKK4", 
          "induction", 
          "transduction", 
          "TRA-8", 
          "monoclonal antibodies", 
          "DIABLO", 
          "mitochondria", 
          "profound loss", 
          "targeting", 
          "antibodies", 
          "chemotherapy agents", 
          "role", 
          "agents", 
          "lines", 
          "activity", 
          "combination", 
          "receptor antibodies", 
          "trails", 
          "release", 
          "loss", 
          "cisplatin", 
          "potential", 
          "different types", 
          "types", 
          "results", 
          "adriamycin", 
          "parallel", 
          "selectivity", 
          "therapy", 
          "efficacy"
        ], 
        "name": "Synergistic induction of tumor cell apoptosis by death receptor antibody and chemotherapy agent through JNK/p38 and mitochondrial death pathway", 
        "pagination": "2034-2044", 
        "productId": [
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1047996205"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1038/sj.onc.1206290"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "12673208"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1038/sj.onc.1206290", 
          "https://app.dimensions.ai/details/publication/pub.1047996205"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2022-05-10T09:54", 
        "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
        "sdPublisher": {
          "name": "Springer Nature - SN SciGraph project", 
          "type": "Organization"
        }, 
        "sdSource": "s3://com-springernature-scigraph/baseset/20220509/entities/gbq_results/article/article_377.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "https://doi.org/10.1038/sj.onc.1206290"
      }
    ]
     

    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/sj.onc.1206290'

    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/sj.onc.1206290'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/sj.onc.1206290'

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

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/sj.onc.1206290'


     

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

    353 TRIPLES      22 PREDICATES      138 URIs      121 LITERALS      41 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1038/sj.onc.1206290 schema:about N0b2454d8661b498181e88591cad7b469
    2 N0e0641be6e314298b96c93ea264bead6
    3 N0f2acf93ef35425b83e4656b9d7b73c6
    4 N0ff6bb7589f8498fa58f63bf382194dd
    5 N128ef3b8dc594dd789a7f9c57c0fe5f9
    6 N180408d84806403eae0c79363eb55c47
    7 N1898e87a97d24bb8abbdd28e266ab96b
    8 N20f7448386514fe884b036dc717f1528
    9 N249c04c4d8af40a58f2c5b9b350934e0
    10 N302e53af571b4aea9067d91191ffc777
    11 N37b3b943b2304a79a3844e99a398253b
    12 N41a05698af774e3a987aa56d3c94636d
    13 N420395ab49354621aa8375f3d4606e50
    14 N49576387beeb4fcabe1e763b9bc58268
    15 N4ee6c149c8d24447ac5bf9e1406435cf
    16 N542361397b8346f0a06692f136cb4812
    17 N5ce89244c09f45b1a7ed3283b39a16bc
    18 N6a871cf9527e406680a5f6676c608667
    19 N6dfbe7b6645d4bed907b4d3487ffbbde
    20 N7f2530ee2db64796b557e02c956b3ed7
    21 N8065e279fd0a4e6688dc22bf50d23b55
    22 N94b1de68afae4b3dbc6b54511be7e95e
    23 N96781d76113b4a339c3e56d0eeb5f0fa
    24 N979c95f5604d43de9e5153758293c8d1
    25 N9a9a2c3724c44ce3ab6b907da0c22aa3
    26 Nb8b9729d5566423ba47913e68def4c1f
    27 Nb965b11534d443ec99a94d7d05ae3a6f
    28 Nbb54a8f311ae4e8483f6d60648c471ec
    29 Nc26f47c09e6246bd9240b587a893c104
    30 Nc95fb52af6ec437fb4cb5f2606796d86
    31 Ncfa04f56d068459795aa1795d7633ce9
    32 Nd40e657ffcd34c22b09d0dd399765f14
    33 Ne0bec7359edc4106bf1e173940eb29ee
    34 Ned2d10004b4d48bfa13092faa8a4964e
    35 anzsrc-for:11
    36 anzsrc-for:1103
    37 anzsrc-for:1112
    38 schema:author N52234d04836b4d76bf642dbd37c4c9a1
    39 schema:citation sg:pub.10.1023/a:1011336726649
    40 sg:pub.10.1038/35008667
    41 sg:pub.10.1038/4723
    42 sg:pub.10.1038/5505
    43 sg:pub.10.1038/5517
    44 sg:pub.10.1038/74994
    45 sg:pub.10.1038/75045
    46 sg:pub.10.1038/91000
    47 schema:datePublished 2003-04-03
    48 schema:datePublishedReg 2003-04-03
    49 schema:description Using two agonistic monoclonal antibodies specific for each death receptor of TRAIL, 2E12 (anti-human DR4) and TRA-8 (anti-human DR5), we examined the signal transduction of the death receptors in combination with or without Q1chemotherapy agents such as Adriamycin (doxorubicin hydrochloride) and Cisplatin. Our results demonstrated that chemotherapy agents were able to enhance apoptosis-inducing activity of these antibodies against several different types of tumor cell lines through enhanced caspase activation. The combination of the antibodies and chemotherapy agents led to a synergistical activation of the JNK/p38 MAP kinase, which was mediated by MKK4. The combination also caused an increased release of cytochrome c and Smac/DIABLO from mitochondria in parallel with the profound loss of mitochondrial membrane potential. These results suggest that the enhanced activation of the JNK/p38 kinase and the mitochondrial apoptosis pathways play a crucial role in synergistic induction of the death receptor-mediated apoptosis by chemotherapy agents. Thus, the simultaneous targeting of cell surface death receptors with agonistic antibodies and the intracellular JNK/p38 and the mitochondrial death pathways with chemotherapy agents would enhance the efficacy and selectivity of both agents in cancer therapy.
    50 schema:genre article
    51 schema:inLanguage en
    52 schema:isAccessibleForFree true
    53 schema:isPartOf N1c865608b29f4e749d387b95c03e3d5b
    54 N22f6157581c8445faf2fa70ee88384fc
    55 sg:journal.1097543
    56 schema:keywords DIABLO
    57 JNK/p38
    58 JNK/p38 MAP kinase
    59 JNK/p38 kinases
    60 MAP kinase
    61 MKK4
    62 Smac/DIABLO
    63 TRA-8
    64 activation
    65 activity
    66 adriamycin
    67 agents
    68 agonistic antibodies
    69 agonistic monoclonal antibody
    70 antibodies
    71 apoptosis
    72 apoptosis pathway
    73 apoptosis-inducing activity
    74 cancer therapy
    75 caspase activation
    76 cell apoptosis
    77 cell lines
    78 cell surface death receptor
    79 chemotherapy agents
    80 cisplatin
    81 combination
    82 crucial role
    83 cytochrome c
    84 death pathways
    85 death receptor-mediated apoptosis
    86 death receptors
    87 different types
    88 efficacy
    89 enhanced activation
    90 induction
    91 kinase
    92 lines
    93 loss
    94 membrane potential
    95 mitochondria
    96 mitochondrial apoptosis pathway
    97 mitochondrial death pathway
    98 mitochondrial membrane potential
    99 monoclonal antibodies
    100 p38
    101 p38 MAP kinase
    102 p38 kinase
    103 parallel
    104 pathway
    105 potential
    106 profound loss
    107 receptor antibodies
    108 receptor-mediated apoptosis
    109 receptors
    110 release
    111 results
    112 role
    113 selectivity
    114 signal transduction
    115 simultaneous targeting
    116 surface death receptor
    117 synergistic induction
    118 targeting
    119 therapy
    120 trails
    121 transduction
    122 tumor cell apoptosis
    123 tumor cell lines
    124 types
    125 schema:name Synergistic induction of tumor cell apoptosis by death receptor antibody and chemotherapy agent through JNK/p38 and mitochondrial death pathway
    126 schema:pagination 2034-2044
    127 schema:productId Na2a4ac5d0dec45bd9cc1c73f619148d9
    128 Naf88aa910a1241d7bfbe7e9180e63405
    129 Ne5e963531eee45e7910db9474d360c3b
    130 schema:sameAs https://app.dimensions.ai/details/publication/pub.1047996205
    131 https://doi.org/10.1038/sj.onc.1206290
    132 schema:sdDatePublished 2022-05-10T09:54
    133 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    134 schema:sdPublisher N25417521490c4fe0b83f82bdee7540ea
    135 schema:url https://doi.org/10.1038/sj.onc.1206290
    136 sgo:license sg:explorer/license/
    137 sgo:sdDataset articles
    138 rdf:type schema:ScholarlyArticle
    139 N0b2454d8661b498181e88591cad7b469 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    140 schema:name Antibodies, Monoclonal
    141 rdf:type schema:DefinedTerm
    142 N0e0641be6e314298b96c93ea264bead6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    143 schema:name Drug Synergism
    144 rdf:type schema:DefinedTerm
    145 N0f2acf93ef35425b83e4656b9d7b73c6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    146 schema:name Intracellular Membranes
    147 rdf:type schema:DefinedTerm
    148 N0ff6bb7589f8498fa58f63bf382194dd schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    149 schema:name Paclitaxel
    150 rdf:type schema:DefinedTerm
    151 N128ef3b8dc594dd789a7f9c57c0fe5f9 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    152 schema:name Mitochondrial Proteins
    153 rdf:type schema:DefinedTerm
    154 N16eeed03891b4973ae41693ec277504c rdf:first sg:person.01137705050.57
    155 rdf:rest N6195cf36b500403f90435259a6bb9f9a
    156 N175d2856f12a4da9b4ba3f5966e40b7e rdf:first sg:person.0755422217.45
    157 rdf:rest N90dda40970264d7f9974f462593baa73
    158 N180408d84806403eae0c79363eb55c47 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    159 schema:name Tumor Cells, Cultured
    160 rdf:type schema:DefinedTerm
    161 N1898e87a97d24bb8abbdd28e266ab96b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    162 schema:name Female
    163 rdf:type schema:DefinedTerm
    164 N1c865608b29f4e749d387b95c03e3d5b schema:volumeNumber 22
    165 rdf:type schema:PublicationVolume
    166 N20f7448386514fe884b036dc717f1528 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    167 schema:name Cisplatin
    168 rdf:type schema:DefinedTerm
    169 N22f6157581c8445faf2fa70ee88384fc schema:issueNumber 13
    170 rdf:type schema:PublicationIssue
    171 N249c04c4d8af40a58f2c5b9b350934e0 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    172 schema:name Receptors, Tumor Necrosis Factor
    173 rdf:type schema:DefinedTerm
    174 N25417521490c4fe0b83f82bdee7540ea schema:name Springer Nature - SN SciGraph project
    175 rdf:type schema:Organization
    176 N302e53af571b4aea9067d91191ffc777 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    177 schema:name Antibody Specificity
    178 rdf:type schema:DefinedTerm
    179 N37b3b943b2304a79a3844e99a398253b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    180 schema:name Membrane Potentials
    181 rdf:type schema:DefinedTerm
    182 N41a05698af774e3a987aa56d3c94636d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    183 schema:name Mitogen-Activated Protein Kinases
    184 rdf:type schema:DefinedTerm
    185 N420395ab49354621aa8375f3d4606e50 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    186 schema:name Humans
    187 rdf:type schema:DefinedTerm
    188 N49576387beeb4fcabe1e763b9bc58268 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    189 schema:name Carrier Proteins
    190 rdf:type schema:DefinedTerm
    191 N4ee6c149c8d24447ac5bf9e1406435cf schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    192 schema:name Adenocarcinoma
    193 rdf:type schema:DefinedTerm
    194 N52234d04836b4d76bf642dbd37c4c9a1 rdf:first sg:person.01217265717.13
    195 rdf:rest N16eeed03891b4973ae41693ec277504c
    196 N542361397b8346f0a06692f136cb4812 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    197 schema:name JNK Mitogen-Activated Protein Kinases
    198 rdf:type schema:DefinedTerm
    199 N5ce89244c09f45b1a7ed3283b39a16bc schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    200 schema:name Enzyme Activation
    201 rdf:type schema:DefinedTerm
    202 N6195cf36b500403f90435259a6bb9f9a rdf:first sg:person.0725160173.26
    203 rdf:rest N175d2856f12a4da9b4ba3f5966e40b7e
    204 N6a871cf9527e406680a5f6676c608667 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    205 schema:name DNA Fragmentation
    206 rdf:type schema:DefinedTerm
    207 N6dfbe7b6645d4bed907b4d3487ffbbde schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    208 schema:name Enzyme Inhibitors
    209 rdf:type schema:DefinedTerm
    210 N7f2530ee2db64796b557e02c956b3ed7 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    211 schema:name MAP Kinase Kinase 4
    212 rdf:type schema:DefinedTerm
    213 N8065e279fd0a4e6688dc22bf50d23b55 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    214 schema:name Breast Neoplasms
    215 rdf:type schema:DefinedTerm
    216 N90dda40970264d7f9974f462593baa73 rdf:first sg:person.01304356355.83
    217 rdf:rest Nee94533bb2b94f1691aea409aeed714b
    218 N94b1de68afae4b3dbc6b54511be7e95e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    219 schema:name Caspases
    220 rdf:type schema:DefinedTerm
    221 N96781d76113b4a339c3e56d0eeb5f0fa schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    222 schema:name Antineoplastic Agents
    223 rdf:type schema:DefinedTerm
    224 N979c95f5604d43de9e5153758293c8d1 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    225 schema:name Mitogen-Activated Protein Kinase Kinases
    226 rdf:type schema:DefinedTerm
    227 N9a9a2c3724c44ce3ab6b907da0c22aa3 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    228 schema:name Mitochondria
    229 rdf:type schema:DefinedTerm
    230 Na2a4ac5d0dec45bd9cc1c73f619148d9 schema:name pubmed_id
    231 schema:value 12673208
    232 rdf:type schema:PropertyValue
    233 Naf88aa910a1241d7bfbe7e9180e63405 schema:name doi
    234 schema:value 10.1038/sj.onc.1206290
    235 rdf:type schema:PropertyValue
    236 Nb8b9729d5566423ba47913e68def4c1f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    237 schema:name MAP Kinase Signaling System
    238 rdf:type schema:DefinedTerm
    239 Nb965b11534d443ec99a94d7d05ae3a6f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    240 schema:name Acetylcysteine
    241 rdf:type schema:DefinedTerm
    242 Nbb54a8f311ae4e8483f6d60648c471ec schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    243 schema:name Cytochrome c Group
    244 rdf:type schema:DefinedTerm
    245 Nc26f47c09e6246bd9240b587a893c104 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    246 schema:name p38 Mitogen-Activated Protein Kinases
    247 rdf:type schema:DefinedTerm
    248 Nc95fb52af6ec437fb4cb5f2606796d86 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    249 schema:name Apoptosis Regulatory Proteins
    250 rdf:type schema:DefinedTerm
    251 Ncfa04f56d068459795aa1795d7633ce9 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    252 schema:name Intracellular Signaling Peptides and Proteins
    253 rdf:type schema:DefinedTerm
    254 Nd40e657ffcd34c22b09d0dd399765f14 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    255 schema:name Apoptosis
    256 rdf:type schema:DefinedTerm
    257 Ne0bec7359edc4106bf1e173940eb29ee schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    258 schema:name Receptors, TNF-Related Apoptosis-Inducing Ligand
    259 rdf:type schema:DefinedTerm
    260 Ne5e963531eee45e7910db9474d360c3b schema:name dimensions_id
    261 schema:value pub.1047996205
    262 rdf:type schema:PropertyValue
    263 Ned2d10004b4d48bfa13092faa8a4964e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    264 schema:name Doxorubicin
    265 rdf:type schema:DefinedTerm
    266 Nee94533bb2b94f1691aea409aeed714b rdf:first sg:person.0664616100.38
    267 rdf:rest rdf:nil
    268 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
    269 schema:name Medical and Health Sciences
    270 rdf:type schema:DefinedTerm
    271 anzsrc-for:1103 schema:inDefinedTermSet anzsrc-for:
    272 schema:name Clinical Sciences
    273 rdf:type schema:DefinedTerm
    274 anzsrc-for:1112 schema:inDefinedTermSet anzsrc-for:
    275 schema:name Oncology and Carcinogenesis
    276 rdf:type schema:DefinedTerm
    277 sg:grant.2440147 http://pending.schema.org/fundedItem sg:pub.10.1038/sj.onc.1206290
    278 rdf:type schema:MonetaryGrant
    279 sg:grant.2440161 http://pending.schema.org/fundedItem sg:pub.10.1038/sj.onc.1206290
    280 rdf:type schema:MonetaryGrant
    281 sg:grant.2567549 http://pending.schema.org/fundedItem sg:pub.10.1038/sj.onc.1206290
    282 rdf:type schema:MonetaryGrant
    283 sg:grant.7133716 http://pending.schema.org/fundedItem sg:pub.10.1038/sj.onc.1206290
    284 rdf:type schema:MonetaryGrant
    285 sg:journal.1097543 schema:issn 0950-9232
    286 1476-5594
    287 schema:name Oncogene
    288 schema:publisher Springer Nature
    289 rdf:type schema:Periodical
    290 sg:person.01137705050.57 schema:affiliation grid-institutes:grid.265892.2
    291 schema:familyName Buchsbaum
    292 schema:givenName Donald
    293 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01137705050.57
    294 rdf:type schema:Person
    295 sg:person.01217265717.13 schema:affiliation grid-institutes:grid.410844.d
    296 schema:familyName Ohtsuka
    297 schema:givenName Toshiaki
    298 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01217265717.13
    299 rdf:type schema:Person
    300 sg:person.01304356355.83 schema:affiliation grid-institutes:grid.265892.2
    301 schema:familyName Kimberly
    302 schema:givenName Robert
    303 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01304356355.83
    304 rdf:type schema:Person
    305 sg:person.0664616100.38 schema:affiliation grid-institutes:grid.265892.2
    306 schema:familyName Zhou
    307 schema:givenName Tong
    308 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0664616100.38
    309 rdf:type schema:Person
    310 sg:person.0725160173.26 schema:affiliation grid-institutes:grid.265892.2
    311 schema:familyName Oliver
    312 schema:givenName Patsy
    313 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0725160173.26
    314 rdf:type schema:Person
    315 sg:person.0755422217.45 schema:affiliation grid-institutes:grid.265892.2
    316 schema:familyName Makhija
    317 schema:givenName Sharmila
    318 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0755422217.45
    319 rdf:type schema:Person
    320 sg:pub.10.1023/a:1011336726649 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006241578
    321 https://doi.org/10.1023/a:1011336726649
    322 rdf:type schema:CreativeWork
    323 sg:pub.10.1038/35008667 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012881410
    324 https://doi.org/10.1038/35008667
    325 rdf:type schema:CreativeWork
    326 sg:pub.10.1038/4723 schema:sameAs https://app.dimensions.ai/details/publication/pub.1001523482
    327 https://doi.org/10.1038/4723
    328 rdf:type schema:CreativeWork
    329 sg:pub.10.1038/5505 schema:sameAs https://app.dimensions.ai/details/publication/pub.1038229847
    330 https://doi.org/10.1038/5505
    331 rdf:type schema:CreativeWork
    332 sg:pub.10.1038/5517 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010598958
    333 https://doi.org/10.1038/5517
    334 rdf:type schema:CreativeWork
    335 sg:pub.10.1038/74994 schema:sameAs https://app.dimensions.ai/details/publication/pub.1019830643
    336 https://doi.org/10.1038/74994
    337 rdf:type schema:CreativeWork
    338 sg:pub.10.1038/75045 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044338034
    339 https://doi.org/10.1038/75045
    340 rdf:type schema:CreativeWork
    341 sg:pub.10.1038/91000 schema:sameAs https://app.dimensions.ai/details/publication/pub.1047281881
    342 https://doi.org/10.1038/91000
    343 rdf:type schema:CreativeWork
    344 grid-institutes:grid.265892.2 schema:alternateName Department of Medicine, University of Alabama at Birmingham, 35294, Birmingham, AL, USA
    345 Department of Radiation Biology, University of Alabama at Birmingham, 35294, Birmingham, AL, USA
    346 Division of Gynecologic Oncology, University of Alabama at Birmingham, 35294, Birmingham, AL, USA
    347 schema:name Department of Medicine, University of Alabama at Birmingham, 35294, Birmingham, AL, USA
    348 Department of Radiation Biology, University of Alabama at Birmingham, 35294, Birmingham, AL, USA
    349 Division of Gynecologic Oncology, University of Alabama at Birmingham, 35294, Birmingham, AL, USA
    350 rdf:type schema:Organization
    351 grid-institutes:grid.410844.d schema:alternateName Biomedical Research Laboratories, Sankyo Co., Ltd, 140–8710, Tokyo, Japan
    352 schema:name Biomedical Research Laboratories, Sankyo Co., Ltd, 140–8710, Tokyo, Japan
    353 rdf:type schema:Organization
     




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


    ...