The X-linked inhibitor of apoptosis protein (XIAP) is up-regulated in metastatic melanoma, and XIAP cleavage by Phenoxodiol is associated with ... View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2007-01-26

AUTHORS

Harriet M Kluger, Mary M McCarthy, Ayesha B Alvero, Mario Sznol, Stephan Ariyan, Robert L Camp, David L Rimm, Gil Mor

ABSTRACT

XIAP up-regulation is associated with chemotherapy resistance. Phenoxodiol causes XIAP degradation and chemotherapy sensitization in ovarian cancer. Here we assessed XIAP expression in melanomas, using tissue microarrays containing 436 melanomas and 336 nevi by a novel method of automated, quantitative analysis (AQUA). We used S100 to define pixels as melanoma (tumor mask) within the array spot, and measured XIAP expression using Cy5-conjugated antibodies within the mask. XIAP expression was significantly higher in melanomas than nevi (P < 0.0001), and higher in metastatic than primary lesions (P < 0.0001). We then assessed a panel of melanoma cell lines for XIAP expression, and found high expression in all cell lines. Three of the cell lines were assessed for Phenoxodiol and Carboplatin sensitivity; all were resistant to Carboplatin and showed variable sensitivity to Phenoxodiol. Pre-treating Phenoxodiol sensitive cells with Phenoxodiol prior to Carboplatin resulted in XIAP degradation, associated with Carboplatin sensitization and apoptosis, whereas exposing Phenoxodiol resistant cells to Phenoxodiol resulted in less XIAP degradation and minimal Carboplatin sensitization. We conclude that XIAP levels in clinical specimens are significantly higher in melanomas than their benign counterparts, and higher in metastatic than in primary specimens, suggesting an association with malignant progression and disease aggression. Melanoma resistance to Carboplatin is possibly due to XIAP over-expression. Phenoxodiol can sensitize melanoma cells to Carboplatin in vitro with corresponding XIAP degradation, although the precise target and mechanism of action of Phenoxodiol are subject to further assessment. Targeting XIAP warrants additional investigation as a therapeutic approach for metastatic melanoma. More... »

PAGES

6

References to SciGraph publications

  • 2004-04-30. Downregulation of Bcl-2, FLIP or IAPs (XIAP and survivin) by siRNAs sensitizes resistant melanoma cells to Apo2L/TRAIL-induced apoptosis in CELL DEATH & DIFFERENTIATION
  • 2000-08-24. Translational upregulation of X-linked inhibitor of apoptosis (XIAP) increases resistance to radiation induced cell death in ONCOGENE
  • 2002-10-21. Automated subcellular localization and quantification of protein expression in tissue microarrays in NATURE MEDICINE
  • 2003-05-01. Phenoxodiol – an isoflavone analog – induces apoptosis in chemoresistant ovarian cancer cells in ONCOGENE
  • 2005-12-02. Targeting XIAP for the treatment of malignancy in CELL DEATH & DIFFERENTIATION
  • 2002-09-05. Expression of inhibitors of apoptosis (IAP) proteins in non-small cell human lung cancer in JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
  • 1990-05. Phase II trial of carboplatin in patients with advanced melanoma in INVESTIGATIONAL NEW DRUGS
  • 2005-02-11. Downregulation of XIAP expression induces apoptosis and enhances chemotherapeutic sensitivity in human gastric cancer cells in CANCER GENE THERAPY
  • 2005-02-01. Validation of pharmacodynamic assays to evaluate the clinical efficacy of an antisense compound (AEG 35156) targeted to the X-linked inhibitor of apoptosis protein XIAP in BRITISH JOURNAL OF CANCER
  • 2001-11-07. Apoptosis and chemoresistance in transgenic cancer models in JOURNAL OF MOLECULAR MEDICINE
  • 2004-07-19. XIAP and survivin as therapeutic targets for radiation sensitization in preclinical models of lung cancer in ONCOGENE
  • 2003-05-19. Apoptosis and melanoma chemoresistance in ONCOGENE
  • 2000-10. The biochemistry of apoptosis in NATURE
  • 2003-05-19. Death receptors and melanoma resistance to apoptosis in ONCOGENE
  • 2005-07-05. Combined effects of GSTP1 and MRP1 in melanoma drug resistance in BRITISH JOURNAL OF CANCER
  • 2005-07. Integrative genomic analyses identify MITF as a lineage survival oncogene amplified in malignant melanoma in NATURE
  • 2004-01-19. cDNA microarray analysis of invasive and tumorigenic phenotypes in a breast cancer model in LABORATORY INVESTIGATION
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/1479-5876-5-6

    DOI

    http://dx.doi.org/10.1186/1479-5876-5-6

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1046017100

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/17257402


    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/2008/1112", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Oncology and Carcinogenesis", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Adolescent", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Adult", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Aged", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Aged, 80 and over", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Apoptosis", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Carboplatin", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cell Line, Tumor", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cell Survival", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Drug Screening Assays, Antitumor", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Drug Synergism", 
            "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": "Isoflavones", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Male", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Melanoma", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Middle Aged", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Neoplasm Metastasis", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Prognosis", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Up-Regulation", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "X-Linked Inhibitor of Apoptosis Protein", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "alternateName": "Department of Medicine, Yale University School of Medicine, 333 Cedar St, 06520, New Haven, CT, USA", 
              "id": "http://www.grid.ac/institutes/grid.47100.32", 
              "name": [
                "Department of Medicine, Yale University School of Medicine, 333 Cedar St, 06520, New Haven, CT, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Kluger", 
            "givenName": "Harriet M", 
            "id": "sg:person.01336750727.45", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01336750727.45"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Medicine, Yale University School of Medicine, 333 Cedar St, 06520, New Haven, CT, USA", 
              "id": "http://www.grid.ac/institutes/grid.47100.32", 
              "name": [
                "Department of Medicine, Yale University School of Medicine, 333 Cedar St, 06520, New Haven, CT, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "McCarthy", 
            "givenName": "Mary M", 
            "id": "sg:person.0621443240.14", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0621443240.14"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Obstetrics & Gynecology, Yale University School of Medicine, 333 Cedar St, 06520, New Haven, CT, USA", 
              "id": "http://www.grid.ac/institutes/grid.47100.32", 
              "name": [
                "Department of Obstetrics & Gynecology, Yale University School of Medicine, 333 Cedar St, 06520, New Haven, CT, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Alvero", 
            "givenName": "Ayesha B", 
            "id": "sg:person.01320742654.32", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01320742654.32"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Medicine, Yale University School of Medicine, 333 Cedar St, 06520, New Haven, CT, USA", 
              "id": "http://www.grid.ac/institutes/grid.47100.32", 
              "name": [
                "Department of Medicine, Yale University School of Medicine, 333 Cedar St, 06520, New Haven, CT, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Sznol", 
            "givenName": "Mario", 
            "id": "sg:person.0706626451.72", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0706626451.72"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Surgery, Yale University School of Medicine, 333 Cedar St, 06520, New Haven, CT, USA", 
              "id": "http://www.grid.ac/institutes/grid.47100.32", 
              "name": [
                "Department of Surgery, Yale University School of Medicine, 333 Cedar St, 06520, New Haven, CT, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Ariyan", 
            "givenName": "Stephan", 
            "id": "sg:person.014265505777.28", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014265505777.28"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Pathology, Yale University School of Medicine, 333 Cedar St, 06520, New Haven, CT, USA", 
              "id": "http://www.grid.ac/institutes/grid.47100.32", 
              "name": [
                "Department of Pathology, Yale University School of Medicine, 333 Cedar St, 06520, New Haven, CT, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Camp", 
            "givenName": "Robert L", 
            "id": "sg:person.012367147604.10", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012367147604.10"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Pathology, Yale University School of Medicine, 333 Cedar St, 06520, New Haven, CT, USA", 
              "id": "http://www.grid.ac/institutes/grid.47100.32", 
              "name": [
                "Department of Pathology, Yale University School of Medicine, 333 Cedar St, 06520, New Haven, CT, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Rimm", 
            "givenName": "David L", 
            "id": "sg:person.0754207153.13", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0754207153.13"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Medicine, Yale University School of Medicine, 333 Cedar St, 06520, New Haven, CT, USA", 
              "id": "http://www.grid.ac/institutes/grid.47100.32", 
              "name": [
                "Department of Medicine, Yale University School of Medicine, 333 Cedar St, 06520, New Haven, CT, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Mor", 
            "givenName": "Gil", 
            "id": "sg:person.010561742344.27", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010561742344.27"
            ], 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "sg:pub.10.1038/35037710", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1003551467", 
              "https://doi.org/10.1038/35037710"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nm791", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1030132345", 
              "https://doi.org/10.1038/nm791"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.cdd.4401826", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1037715622", 
              "https://doi.org/10.1038/sj.cdd.4401826"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.onc.1203765", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1032871082", 
              "https://doi.org/10.1038/sj.onc.1203765"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.onc.1207929", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1011261851", 
              "https://doi.org/10.1038/sj.onc.1207929"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/labinvest.3700044", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1018479971", 
              "https://doi.org/10.1038/labinvest.3700044"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.bjc.6602363", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1048363663", 
              "https://doi.org/10.1038/sj.bjc.6602363"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.cdd.4401416", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1038685270", 
              "https://doi.org/10.1038/sj.cdd.4401416"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s00109-001-0293-3", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1053454068", 
              "https://doi.org/10.1007/s00109-001-0293-3"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.cgt.7700813", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1021323231", 
              "https://doi.org/10.1038/sj.cgt.7700813"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/bf00177256", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1034353954", 
              "https://doi.org/10.1007/bf00177256"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.onc.1206456", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1035173994", 
              "https://doi.org/10.1038/sj.onc.1206456"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.onc.1206422", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1013762965", 
              "https://doi.org/10.1038/sj.onc.1206422"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s00432-002-0364-z", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1010790395", 
              "https://doi.org/10.1007/s00432-002-0364-z"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature03664", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1016552205", 
              "https://doi.org/10.1038/nature03664"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.onc.1206454", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1051330539", 
              "https://doi.org/10.1038/sj.onc.1206454"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.bjc.6602681", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1038093871", 
              "https://doi.org/10.1038/sj.bjc.6602681"
            ], 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "2007-01-26", 
        "datePublishedReg": "2007-01-26", 
        "description": "XIAP up-regulation is associated with chemotherapy resistance. Phenoxodiol causes XIAP degradation and chemotherapy sensitization in ovarian cancer. Here we assessed XIAP expression in melanomas, using tissue microarrays containing 436 melanomas and 336 nevi by a novel method of automated, quantitative analysis (AQUA). We used S100 to define pixels as melanoma (tumor mask) within the array spot, and measured XIAP expression using Cy5-conjugated antibodies within the mask. XIAP expression was significantly higher in melanomas than nevi (P < 0.0001), and higher in metastatic than primary lesions (P < 0.0001). We then assessed a panel of melanoma cell lines for XIAP expression, and found high expression in all cell lines. Three of the cell lines were assessed for Phenoxodiol and Carboplatin sensitivity; all were resistant to Carboplatin and showed variable sensitivity to Phenoxodiol. Pre-treating Phenoxodiol sensitive cells with Phenoxodiol prior to Carboplatin resulted in XIAP degradation, associated with Carboplatin sensitization and apoptosis, whereas exposing Phenoxodiol resistant cells to Phenoxodiol resulted in less XIAP degradation and minimal Carboplatin sensitization. We conclude that XIAP levels in clinical specimens are significantly higher in melanomas than their benign counterparts, and higher in metastatic than in primary specimens, suggesting an association with malignant progression and disease aggression. Melanoma resistance to Carboplatin is possibly due to XIAP over-expression. Phenoxodiol can sensitize melanoma cells to Carboplatin in vitro with corresponding XIAP degradation, although the precise target and mechanism of action of Phenoxodiol are subject to further assessment. Targeting XIAP warrants additional investigation as a therapeutic approach for metastatic melanoma.", 
        "genre": "article", 
        "id": "sg:pub.10.1186/1479-5876-5-6", 
        "isAccessibleForFree": true, 
        "isFundedItemOf": [
          {
            "id": "sg:grant.2412545", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.2475698", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.2478248", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.2478108", 
            "type": "MonetaryGrant"
          }, 
          {
            "id": "sg:grant.2438746", 
            "type": "MonetaryGrant"
          }
        ], 
        "isPartOf": [
          {
            "id": "sg:journal.1032886", 
            "issn": [
              "1479-5876"
            ], 
            "name": "Journal of Translational Medicine", 
            "publisher": "Springer Nature", 
            "type": "Periodical"
          }, 
          {
            "issueNumber": "1", 
            "type": "PublicationIssue"
          }, 
          {
            "type": "PublicationVolume", 
            "volumeNumber": "5"
          }
        ], 
        "keywords": [
          "metastatic melanoma", 
          "XIAP expression", 
          "cell lines", 
          "Cy5-conjugated antibodies", 
          "mechanism of action", 
          "melanoma cell lines", 
          "primary lesion", 
          "ovarian cancer", 
          "therapeutic approaches", 
          "tissue microarray", 
          "disease aggression", 
          "carboplatin sensitivity", 
          "chemotherapy resistance", 
          "malignant progression", 
          "clinical specimens", 
          "melanoma", 
          "carboplatin", 
          "benign counterparts", 
          "chemotherapy sensitization", 
          "primary specimens", 
          "phenoxodiol", 
          "resistant cells", 
          "melanoma cells", 
          "high expression", 
          "melanoma resistance", 
          "sensitization", 
          "further assessment", 
          "metastatic", 
          "sensitive cells", 
          "additional investigation", 
          "XIAP degradation", 
          "variable sensitivity", 
          "XIAP levels", 
          "XIAP", 
          "apoptosis protein", 
          "precise targets", 
          "expression", 
          "cells", 
          "lesions", 
          "cancer", 
          "nevi", 
          "S100", 
          "progression", 
          "antibodies", 
          "apoptosis", 
          "inhibitors", 
          "association", 
          "specimens", 
          "sensitivity", 
          "resistance", 
          "microarray", 
          "lines", 
          "assessment", 
          "target", 
          "levels", 
          "protein", 
          "quantitative analysis", 
          "action", 
          "regulation", 
          "panel", 
          "aggression", 
          "mechanism", 
          "array spots", 
          "investigation", 
          "analysis", 
          "mask", 
          "counterparts", 
          "degradation", 
          "spots", 
          "method", 
          "approach", 
          "novel method", 
          "pixels"
        ], 
        "name": "The X-linked inhibitor of apoptosis protein (XIAP) is up-regulated in metastatic melanoma, and XIAP cleavage by Phenoxodiol is associated with Carboplatin sensitization", 
        "pagination": "6", 
        "productId": [
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1046017100"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1186/1479-5876-5-6"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "17257402"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1186/1479-5876-5-6", 
          "https://app.dimensions.ai/details/publication/pub.1046017100"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2022-09-02T15:52", 
        "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
        "sdPublisher": {
          "name": "Springer Nature - SN SciGraph project", 
          "type": "Organization"
        }, 
        "sdSource": "s3://com-springernature-scigraph/baseset/20220902/entities/gbq_results/article/article_454.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "https://doi.org/10.1186/1479-5876-5-6"
      }
    ]
     

    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.10.1186/1479-5876-5-6'

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

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1186/1479-5876-5-6'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1186/1479-5876-5-6'

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

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1186/1479-5876-5-6'


     

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

    346 TRIPLES      21 PREDICATES      135 URIs      110 LITERALS      27 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1186/1479-5876-5-6 schema:about N23cf758e144744a7b59819f45fddca55
    2 N26bb4663d6614895a7ea1506f9cc9699
    3 N3d67f1c3a9474c32b44fbd6827b18a2d
    4 N432c018125db44a19d00973a551a0d85
    5 N45a1cc238d544d4b9c929b674fcb6e61
    6 N4fbd8f0d98ae463e80d1c54e59fa52df
    7 N661735916a834ce6a5f2cf8d2781680b
    8 N6f2f512dddeb43b48d0d6e2c1fc3a11a
    9 N7a864fb43b12408bb0ce8b065967417a
    10 N88e83d5bce3a4eca8d857dacd5132ea9
    11 N89c155978e8243778e1a78d475f4c28d
    12 N987cb7a6f3c44f829deb0e9109aceffa
    13 N9f9b0b0838f24e85b7544708f45746f2
    14 Nb2e0f9793b424e6898e047b6a48633db
    15 Nb66f942236fa481380bcb26acfb55bc6
    16 Ndb186ed997264d888cc711da3331beea
    17 Neab800e343e049dbaa7a2d0f1a53fa85
    18 Nef49deab8f204f5a9c05ef4d4142ea73
    19 Nf1c6d90c867d469397510b7599a5a3f7
    20 Nf8e9ee2c81854a70a272323d9513512b
    21 anzsrc-for:11
    22 anzsrc-for:1112
    23 schema:author Nfa70ce1f979f4f098f65fa69ff723497
    24 schema:citation sg:pub.10.1007/bf00177256
    25 sg:pub.10.1007/s00109-001-0293-3
    26 sg:pub.10.1007/s00432-002-0364-z
    27 sg:pub.10.1038/35037710
    28 sg:pub.10.1038/labinvest.3700044
    29 sg:pub.10.1038/nature03664
    30 sg:pub.10.1038/nm791
    31 sg:pub.10.1038/sj.bjc.6602363
    32 sg:pub.10.1038/sj.bjc.6602681
    33 sg:pub.10.1038/sj.cdd.4401416
    34 sg:pub.10.1038/sj.cdd.4401826
    35 sg:pub.10.1038/sj.cgt.7700813
    36 sg:pub.10.1038/sj.onc.1203765
    37 sg:pub.10.1038/sj.onc.1206422
    38 sg:pub.10.1038/sj.onc.1206454
    39 sg:pub.10.1038/sj.onc.1206456
    40 sg:pub.10.1038/sj.onc.1207929
    41 schema:datePublished 2007-01-26
    42 schema:datePublishedReg 2007-01-26
    43 schema:description XIAP up-regulation is associated with chemotherapy resistance. Phenoxodiol causes XIAP degradation and chemotherapy sensitization in ovarian cancer. Here we assessed XIAP expression in melanomas, using tissue microarrays containing 436 melanomas and 336 nevi by a novel method of automated, quantitative analysis (AQUA). We used S100 to define pixels as melanoma (tumor mask) within the array spot, and measured XIAP expression using Cy5-conjugated antibodies within the mask. XIAP expression was significantly higher in melanomas than nevi (P < 0.0001), and higher in metastatic than primary lesions (P < 0.0001). We then assessed a panel of melanoma cell lines for XIAP expression, and found high expression in all cell lines. Three of the cell lines were assessed for Phenoxodiol and Carboplatin sensitivity; all were resistant to Carboplatin and showed variable sensitivity to Phenoxodiol. Pre-treating Phenoxodiol sensitive cells with Phenoxodiol prior to Carboplatin resulted in XIAP degradation, associated with Carboplatin sensitization and apoptosis, whereas exposing Phenoxodiol resistant cells to Phenoxodiol resulted in less XIAP degradation and minimal Carboplatin sensitization. We conclude that XIAP levels in clinical specimens are significantly higher in melanomas than their benign counterparts, and higher in metastatic than in primary specimens, suggesting an association with malignant progression and disease aggression. Melanoma resistance to Carboplatin is possibly due to XIAP over-expression. Phenoxodiol can sensitize melanoma cells to Carboplatin in vitro with corresponding XIAP degradation, although the precise target and mechanism of action of Phenoxodiol are subject to further assessment. Targeting XIAP warrants additional investigation as a therapeutic approach for metastatic melanoma.
    44 schema:genre article
    45 schema:isAccessibleForFree true
    46 schema:isPartOf N4104a30cf14245c5810a1b7f62cf75c1
    47 Nda14626e1dba4f72a6baff001eed2b9b
    48 sg:journal.1032886
    49 schema:keywords Cy5-conjugated antibodies
    50 S100
    51 XIAP
    52 XIAP degradation
    53 XIAP expression
    54 XIAP levels
    55 action
    56 additional investigation
    57 aggression
    58 analysis
    59 antibodies
    60 apoptosis
    61 apoptosis protein
    62 approach
    63 array spots
    64 assessment
    65 association
    66 benign counterparts
    67 cancer
    68 carboplatin
    69 carboplatin sensitivity
    70 cell lines
    71 cells
    72 chemotherapy resistance
    73 chemotherapy sensitization
    74 clinical specimens
    75 counterparts
    76 degradation
    77 disease aggression
    78 expression
    79 further assessment
    80 high expression
    81 inhibitors
    82 investigation
    83 lesions
    84 levels
    85 lines
    86 malignant progression
    87 mask
    88 mechanism
    89 mechanism of action
    90 melanoma
    91 melanoma cell lines
    92 melanoma cells
    93 melanoma resistance
    94 metastatic
    95 metastatic melanoma
    96 method
    97 microarray
    98 nevi
    99 novel method
    100 ovarian cancer
    101 panel
    102 phenoxodiol
    103 pixels
    104 precise targets
    105 primary lesion
    106 primary specimens
    107 progression
    108 protein
    109 quantitative analysis
    110 regulation
    111 resistance
    112 resistant cells
    113 sensitive cells
    114 sensitivity
    115 sensitization
    116 specimens
    117 spots
    118 target
    119 therapeutic approaches
    120 tissue microarray
    121 variable sensitivity
    122 schema:name The X-linked inhibitor of apoptosis protein (XIAP) is up-regulated in metastatic melanoma, and XIAP cleavage by Phenoxodiol is associated with Carboplatin sensitization
    123 schema:pagination 6
    124 schema:productId N8fa11e7e133348d68f423c4066701aab
    125 Nd16d512775ab4f9ca013c8c1199313c1
    126 Nf5e713acd66d40dfb459bd7e286963e8
    127 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046017100
    128 https://doi.org/10.1186/1479-5876-5-6
    129 schema:sdDatePublished 2022-09-02T15:52
    130 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    131 schema:sdPublisher N09e8764abeec4573ba304c5cec15c7e4
    132 schema:url https://doi.org/10.1186/1479-5876-5-6
    133 sgo:license sg:explorer/license/
    134 sgo:sdDataset articles
    135 rdf:type schema:ScholarlyArticle
    136 N09e8764abeec4573ba304c5cec15c7e4 schema:name Springer Nature - SN SciGraph project
    137 rdf:type schema:Organization
    138 N23cf758e144744a7b59819f45fddca55 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    139 schema:name Cell Line, Tumor
    140 rdf:type schema:DefinedTerm
    141 N26bb4663d6614895a7ea1506f9cc9699 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    142 schema:name Isoflavones
    143 rdf:type schema:DefinedTerm
    144 N34979a5d998a4c78b497240e3bfdfd38 rdf:first sg:person.01320742654.32
    145 rdf:rest Nfefa3f1a2aee489b8d29cf1f9455741c
    146 N355c6cac502f49018d4881e922563dee rdf:first sg:person.010561742344.27
    147 rdf:rest rdf:nil
    148 N3d67f1c3a9474c32b44fbd6827b18a2d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    149 schema:name Adult
    150 rdf:type schema:DefinedTerm
    151 N4104a30cf14245c5810a1b7f62cf75c1 schema:issueNumber 1
    152 rdf:type schema:PublicationIssue
    153 N432c018125db44a19d00973a551a0d85 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    154 schema:name Melanoma
    155 rdf:type schema:DefinedTerm
    156 N45a1cc238d544d4b9c929b674fcb6e61 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    157 schema:name Up-Regulation
    158 rdf:type schema:DefinedTerm
    159 N46e40c21bb3a4f7198ab9e8ac5993aea rdf:first sg:person.0621443240.14
    160 rdf:rest N34979a5d998a4c78b497240e3bfdfd38
    161 N4fbd8f0d98ae463e80d1c54e59fa52df schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    162 schema:name X-Linked Inhibitor of Apoptosis Protein
    163 rdf:type schema:DefinedTerm
    164 N661735916a834ce6a5f2cf8d2781680b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    165 schema:name Middle Aged
    166 rdf:type schema:DefinedTerm
    167 N6f2f512dddeb43b48d0d6e2c1fc3a11a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    168 schema:name Carboplatin
    169 rdf:type schema:DefinedTerm
    170 N7a864fb43b12408bb0ce8b065967417a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    171 schema:name Apoptosis
    172 rdf:type schema:DefinedTerm
    173 N88e83d5bce3a4eca8d857dacd5132ea9 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    174 schema:name Female
    175 rdf:type schema:DefinedTerm
    176 N89c155978e8243778e1a78d475f4c28d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    177 schema:name Drug Screening Assays, Antitumor
    178 rdf:type schema:DefinedTerm
    179 N8fa11e7e133348d68f423c4066701aab schema:name dimensions_id
    180 schema:value pub.1046017100
    181 rdf:type schema:PropertyValue
    182 N987cb7a6f3c44f829deb0e9109aceffa schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    183 schema:name Aged, 80 and over
    184 rdf:type schema:DefinedTerm
    185 N9f9b0b0838f24e85b7544708f45746f2 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    186 schema:name Neoplasm Metastasis
    187 rdf:type schema:DefinedTerm
    188 Nb2e0f9793b424e6898e047b6a48633db schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    189 schema:name Humans
    190 rdf:type schema:DefinedTerm
    191 Nb66f942236fa481380bcb26acfb55bc6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    192 schema:name Adolescent
    193 rdf:type schema:DefinedTerm
    194 Nc910fbf959e640d88b903d8900a746d7 rdf:first sg:person.014265505777.28
    195 rdf:rest Ne39f1fce091a4bbe8730dcb62504f4b9
    196 Nd16d512775ab4f9ca013c8c1199313c1 schema:name pubmed_id
    197 schema:value 17257402
    198 rdf:type schema:PropertyValue
    199 Nda14626e1dba4f72a6baff001eed2b9b schema:volumeNumber 5
    200 rdf:type schema:PublicationVolume
    201 Ndb186ed997264d888cc711da3331beea schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    202 schema:name Male
    203 rdf:type schema:DefinedTerm
    204 Ne39f1fce091a4bbe8730dcb62504f4b9 rdf:first sg:person.012367147604.10
    205 rdf:rest Nf0d8627b1aa74df3a66c675b878c0f6a
    206 Neab800e343e049dbaa7a2d0f1a53fa85 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    207 schema:name Cell Survival
    208 rdf:type schema:DefinedTerm
    209 Nef49deab8f204f5a9c05ef4d4142ea73 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    210 schema:name Drug Synergism
    211 rdf:type schema:DefinedTerm
    212 Nf0d8627b1aa74df3a66c675b878c0f6a rdf:first sg:person.0754207153.13
    213 rdf:rest N355c6cac502f49018d4881e922563dee
    214 Nf1c6d90c867d469397510b7599a5a3f7 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    215 schema:name Aged
    216 rdf:type schema:DefinedTerm
    217 Nf5e713acd66d40dfb459bd7e286963e8 schema:name doi
    218 schema:value 10.1186/1479-5876-5-6
    219 rdf:type schema:PropertyValue
    220 Nf8e9ee2c81854a70a272323d9513512b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    221 schema:name Prognosis
    222 rdf:type schema:DefinedTerm
    223 Nfa70ce1f979f4f098f65fa69ff723497 rdf:first sg:person.01336750727.45
    224 rdf:rest N46e40c21bb3a4f7198ab9e8ac5993aea
    225 Nfefa3f1a2aee489b8d29cf1f9455741c rdf:first sg:person.0706626451.72
    226 rdf:rest Nc910fbf959e640d88b903d8900a746d7
    227 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
    228 schema:name Medical and Health Sciences
    229 rdf:type schema:DefinedTerm
    230 anzsrc-for:1112 schema:inDefinedTermSet anzsrc-for:
    231 schema:name Oncology and Carcinogenesis
    232 rdf:type schema:DefinedTerm
    233 sg:grant.2412545 http://pending.schema.org/fundedItem sg:pub.10.1186/1479-5876-5-6
    234 rdf:type schema:MonetaryGrant
    235 sg:grant.2438746 http://pending.schema.org/fundedItem sg:pub.10.1186/1479-5876-5-6
    236 rdf:type schema:MonetaryGrant
    237 sg:grant.2475698 http://pending.schema.org/fundedItem sg:pub.10.1186/1479-5876-5-6
    238 rdf:type schema:MonetaryGrant
    239 sg:grant.2478108 http://pending.schema.org/fundedItem sg:pub.10.1186/1479-5876-5-6
    240 rdf:type schema:MonetaryGrant
    241 sg:grant.2478248 http://pending.schema.org/fundedItem sg:pub.10.1186/1479-5876-5-6
    242 rdf:type schema:MonetaryGrant
    243 sg:journal.1032886 schema:issn 1479-5876
    244 schema:name Journal of Translational Medicine
    245 schema:publisher Springer Nature
    246 rdf:type schema:Periodical
    247 sg:person.010561742344.27 schema:affiliation grid-institutes:grid.47100.32
    248 schema:familyName Mor
    249 schema:givenName Gil
    250 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010561742344.27
    251 rdf:type schema:Person
    252 sg:person.012367147604.10 schema:affiliation grid-institutes:grid.47100.32
    253 schema:familyName Camp
    254 schema:givenName Robert L
    255 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012367147604.10
    256 rdf:type schema:Person
    257 sg:person.01320742654.32 schema:affiliation grid-institutes:grid.47100.32
    258 schema:familyName Alvero
    259 schema:givenName Ayesha B
    260 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01320742654.32
    261 rdf:type schema:Person
    262 sg:person.01336750727.45 schema:affiliation grid-institutes:grid.47100.32
    263 schema:familyName Kluger
    264 schema:givenName Harriet M
    265 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01336750727.45
    266 rdf:type schema:Person
    267 sg:person.014265505777.28 schema:affiliation grid-institutes:grid.47100.32
    268 schema:familyName Ariyan
    269 schema:givenName Stephan
    270 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014265505777.28
    271 rdf:type schema:Person
    272 sg:person.0621443240.14 schema:affiliation grid-institutes:grid.47100.32
    273 schema:familyName McCarthy
    274 schema:givenName Mary M
    275 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0621443240.14
    276 rdf:type schema:Person
    277 sg:person.0706626451.72 schema:affiliation grid-institutes:grid.47100.32
    278 schema:familyName Sznol
    279 schema:givenName Mario
    280 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0706626451.72
    281 rdf:type schema:Person
    282 sg:person.0754207153.13 schema:affiliation grid-institutes:grid.47100.32
    283 schema:familyName Rimm
    284 schema:givenName David L
    285 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0754207153.13
    286 rdf:type schema:Person
    287 sg:pub.10.1007/bf00177256 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034353954
    288 https://doi.org/10.1007/bf00177256
    289 rdf:type schema:CreativeWork
    290 sg:pub.10.1007/s00109-001-0293-3 schema:sameAs https://app.dimensions.ai/details/publication/pub.1053454068
    291 https://doi.org/10.1007/s00109-001-0293-3
    292 rdf:type schema:CreativeWork
    293 sg:pub.10.1007/s00432-002-0364-z schema:sameAs https://app.dimensions.ai/details/publication/pub.1010790395
    294 https://doi.org/10.1007/s00432-002-0364-z
    295 rdf:type schema:CreativeWork
    296 sg:pub.10.1038/35037710 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003551467
    297 https://doi.org/10.1038/35037710
    298 rdf:type schema:CreativeWork
    299 sg:pub.10.1038/labinvest.3700044 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018479971
    300 https://doi.org/10.1038/labinvest.3700044
    301 rdf:type schema:CreativeWork
    302 sg:pub.10.1038/nature03664 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016552205
    303 https://doi.org/10.1038/nature03664
    304 rdf:type schema:CreativeWork
    305 sg:pub.10.1038/nm791 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030132345
    306 https://doi.org/10.1038/nm791
    307 rdf:type schema:CreativeWork
    308 sg:pub.10.1038/sj.bjc.6602363 schema:sameAs https://app.dimensions.ai/details/publication/pub.1048363663
    309 https://doi.org/10.1038/sj.bjc.6602363
    310 rdf:type schema:CreativeWork
    311 sg:pub.10.1038/sj.bjc.6602681 schema:sameAs https://app.dimensions.ai/details/publication/pub.1038093871
    312 https://doi.org/10.1038/sj.bjc.6602681
    313 rdf:type schema:CreativeWork
    314 sg:pub.10.1038/sj.cdd.4401416 schema:sameAs https://app.dimensions.ai/details/publication/pub.1038685270
    315 https://doi.org/10.1038/sj.cdd.4401416
    316 rdf:type schema:CreativeWork
    317 sg:pub.10.1038/sj.cdd.4401826 schema:sameAs https://app.dimensions.ai/details/publication/pub.1037715622
    318 https://doi.org/10.1038/sj.cdd.4401826
    319 rdf:type schema:CreativeWork
    320 sg:pub.10.1038/sj.cgt.7700813 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021323231
    321 https://doi.org/10.1038/sj.cgt.7700813
    322 rdf:type schema:CreativeWork
    323 sg:pub.10.1038/sj.onc.1203765 schema:sameAs https://app.dimensions.ai/details/publication/pub.1032871082
    324 https://doi.org/10.1038/sj.onc.1203765
    325 rdf:type schema:CreativeWork
    326 sg:pub.10.1038/sj.onc.1206422 schema:sameAs https://app.dimensions.ai/details/publication/pub.1013762965
    327 https://doi.org/10.1038/sj.onc.1206422
    328 rdf:type schema:CreativeWork
    329 sg:pub.10.1038/sj.onc.1206454 schema:sameAs https://app.dimensions.ai/details/publication/pub.1051330539
    330 https://doi.org/10.1038/sj.onc.1206454
    331 rdf:type schema:CreativeWork
    332 sg:pub.10.1038/sj.onc.1206456 schema:sameAs https://app.dimensions.ai/details/publication/pub.1035173994
    333 https://doi.org/10.1038/sj.onc.1206456
    334 rdf:type schema:CreativeWork
    335 sg:pub.10.1038/sj.onc.1207929 schema:sameAs https://app.dimensions.ai/details/publication/pub.1011261851
    336 https://doi.org/10.1038/sj.onc.1207929
    337 rdf:type schema:CreativeWork
    338 grid-institutes:grid.47100.32 schema:alternateName Department of Medicine, Yale University School of Medicine, 333 Cedar St, 06520, New Haven, CT, USA
    339 Department of Obstetrics & Gynecology, Yale University School of Medicine, 333 Cedar St, 06520, New Haven, CT, USA
    340 Department of Pathology, Yale University School of Medicine, 333 Cedar St, 06520, New Haven, CT, USA
    341 Department of Surgery, Yale University School of Medicine, 333 Cedar St, 06520, New Haven, CT, USA
    342 schema:name Department of Medicine, Yale University School of Medicine, 333 Cedar St, 06520, New Haven, CT, USA
    343 Department of Obstetrics & Gynecology, Yale University School of Medicine, 333 Cedar St, 06520, New Haven, CT, USA
    344 Department of Pathology, Yale University School of Medicine, 333 Cedar St, 06520, New Haven, CT, USA
    345 Department of Surgery, Yale University School of Medicine, 333 Cedar St, 06520, New Haven, CT, USA
    346 rdf:type schema:Organization
     




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


    ...