Trastuzumab Plus Tamoxifen: Anti-Proliferative and Molecular Interactions in Breast Carcinoma View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2004-07

AUTHORS

Santiago Ropero, Javier Abel Menéndez, Alejandro Vázquez-Martín, Sagrario Montero, Hernán Cortés-Funes, Ramon Colomer

ABSTRACT

HER2 overexpression has been associated with anti-estrogen resistance in human breast cancer, and it has been suggested that the combined treatment of an anti-HER2 antibody plus tamoxifen has enhanced anti-cancer efficacy in breast cancer. The detailed anti-proliferative interactions between trastuzumab and tamoxifen were analyzed with the isobologram and Chou and Talalay methods, which assess the presence of synergy, addition or antagonism. We used the breast cancer cell lines that are estrogen receptor (ER)-positive and HER2-positive. We also analyzed the molecular changes on the HER2 and (ER) signaling pathways that are induced by trastuzumab plus tamoxifen. In terms of cancer cell proliferation, the simultaneous combination of trastuzumab and tamoxifen on BT-474 cells was more growth inhibitory (44%) than the treatment with trastuzumab (24%) or tamoxifen (31%) alone. Isobologram analysis of simultaneous trastuzumab plus tamoxifen exposure showed, however, that there were antagonistic interactions at an effect level of 30% (IC30). Using Chou and Talalay analysis we also observed antagonistic interactions at lower levels of cell kill, although there were additive effects at highest levels of cell kill. Trastuzumab followed by tamoxifen showed antagonism at all effects levels. Tamoxifen followed by trastuzumab showed antagonism at lower levels of cell kill, and additivity at higher levels of cell kill. Similar interactions were observed using T47D cells. The molecular effects of the combined treatment with trastuzumab plus tamoxifen on the levels of HER2 and ER signaling showed that, with respect to HER2 protein levels, trastuzumab downregulated HER2 by 27%, tamoxifen upregulated HER2 by 40%, and the combination of trastuzumab plus tamoxifen did not induce changes in HER2 respect to control. With respect to HER2 mRNA, trastuzumab upregulated HER2 mRNA to 367%, tamoxifen to 166%, and the combination to 401%. With respect to HER2 phosphorylation, trastuzumab upregulated HER2 phosphorylation to 352%, tamoxifen to 202% and the combination to 633%. Epidermal growth factor receptor levels were not changed by trastuzumab or tamoxifen alone, and were upregulated to 138% by the combination. The protein levels and activity of extracellular recptor kinase were not modified by trastuzumab, tamoxifen or the combination. Finally, estrogen receptor protein and mRNA levels were downregulated to about 50% by trastuzumab, tamoxifen or the combination. Taken together, our results show that in ER-positive breast cancer cells overexpressing HER2, trastuzumab plus tamoxifen have antagonistic interactions when used in combination, and that this antagonism may be related with an increase in HER2 signaling pathways that occurs when tamoxifen is added to trastuzumab. More... »

PAGES

125-137

References to SciGraph publications

  • 1993-07. Differential responses of human tumor cell lines to anti-p185HER2 monoclonal antibodies in CANCER IMMUNOLOGY, IMMUNOTHERAPY
  • 2000-12. Overexpression of ErbB2 in cancer and ErbB2-targeting strategies in ONCOGENE
  • 2000-01. Anti-HER2 antibody enhances the growth inhibitory effect of anti-oestrogen on breast cancer cells expressing both oestrogen receptors and HER2 in BRITISH JOURNAL OF CANCER
  • 1997-01. Enhanced anti-proliferative activity of the combination of tamoxifen plus HER-2-neu antibody in BREAST CANCER RESEARCH AND TREATMENT
  • 1999-04. Inhibitory effects of combinations of HER-2/neu antibody and chemotherapeutic agents used for treatment of human breast cancers in ONCOGENE
  • 1993-01. The role of erbB2 signal transduction pathways in human breast cancer in BREAST CANCER RESEARCH AND TREATMENT
  • 1996-06. In vitro and in vivo anti-tumour effects of a humanised monoclonal antibody against c-erbB-2 product in BRITISH JOURNAL OF CANCER
  • 1999-11. Acquired antiestrogen resistance in MCF-7 human breast cancer sublines is not accomplished by altered expression of receptors in the ErbB-family in BREAST CANCER RESEARCH AND TREATMENT
  • 1999-11. The pure antiestrogen ICI 182780 is more effective in the induction of apoptosis and down regulation of BCL‐2 than tamoxifen in MCF‐7 cells in BREAST CANCER RESEARCH AND TREATMENT
  • 2002-04. Synergistic Interaction Between Vinorelbine and Gamma-Linolenic Acid in Breast Cancer Cells in BREAST CANCER RESEARCH AND TREATMENT
  • 1991. Anti-p185HER2 monoclonal antibodies: Biological properties and potential for immunotherapy in GENES, ONCOGENES, AND HORMONES
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1023/b:brea.0000032981.20384.c6

    DOI

    http://dx.doi.org/10.1023/b:brea.0000032981.20384.c6

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1015046659

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/15319565


    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": "Antibodies, Monoclonal", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Antibodies, Monoclonal, Humanized", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Antineoplastic Agents", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Antineoplastic Agents, Hormonal", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Breast Neoplasms", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cell Division", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Drug Interactions", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Female", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Genes, erbB-2", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Humans", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "RNA, Messenger", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Receptor, ErbB-2", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Receptors, Estrogen", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Signal Transduction", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Tamoxifen", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Trastuzumab", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Tumor Cells, Cultured", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Up-Regulation", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "alternateName": "Hospital Universitario 12 De Octubre", 
              "id": "https://www.grid.ac/institutes/grid.144756.5", 
              "name": [
                "Division of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Ropero", 
            "givenName": "Santiago", 
            "id": "sg:person.01236543376.53", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01236543376.53"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Hospital Universitario 12 De Octubre", 
              "id": "https://www.grid.ac/institutes/grid.144756.5", 
              "name": [
                "Division of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Abel Men\u00e9ndez", 
            "givenName": "Javier", 
            "id": "sg:person.01233311174.22", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01233311174.22"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Hospital Universitario 12 De Octubre", 
              "id": "https://www.grid.ac/institutes/grid.144756.5", 
              "name": [
                "Division of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain"
              ], 
              "type": "Organization"
            }, 
            "familyName": "V\u00e1zquez-Mart\u00edn", 
            "givenName": "Alejandro", 
            "id": "sg:person.01163643102.17", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01163643102.17"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Hospital Universitario 12 De Octubre", 
              "id": "https://www.grid.ac/institutes/grid.144756.5", 
              "name": [
                "Division of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Montero", 
            "givenName": "Sagrario", 
            "id": "sg:person.01305162525.50", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01305162525.50"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Hospital Universitario 12 De Octubre", 
              "id": "https://www.grid.ac/institutes/grid.144756.5", 
              "name": [
                "Division of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Cort\u00e9s-Funes", 
            "givenName": "Hern\u00e1n", 
            "id": "sg:person.01352043071.09", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01352043071.09"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Hospital Universitari de Girona Doctor Josep Trueta", 
              "id": "https://www.grid.ac/institutes/grid.411295.a", 
              "name": [
                "Division of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain", 
                "Division of Medical Oncology, Institut Catala Oncologia, Hospital Josep Trueta, Av. Fran\u00e7a s/n, 17007, Girona, Spain"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Colomer", 
            "givenName": "Ramon", 
            "id": "sg:person.0766655346.71", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0766655346.71"
            ], 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "sg:pub.10.1038/sj.onc.1202526", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1001624052", 
              "https://doi.org/10.1038/sj.onc.1202526"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.onc.1202526", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1001624052", 
              "https://doi.org/10.1038/sj.onc.1202526"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.onc.1203972", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1002227737", 
              "https://doi.org/10.1038/sj.onc.1203972"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.onc.1203972", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1002227737", 
              "https://doi.org/10.1038/sj.onc.1203972"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/s0959-8049(05)80045-0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1010068198"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/(sici)1521-1878(199801)20:1<41::aid-bies7>3.0.co;2-v", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1013765345"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/978-1-4615-3500-3_10", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1014349003", 
              "https://doi.org/10.1007/978-1-4615-3500-3_10"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/978-1-4615-3500-3_10", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1014349003", 
              "https://doi.org/10.1007/978-1-4615-3500-3_10"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/s0304-419x(97)00032-2", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1020171474"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1073/pnas.87.7.2569", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1021476395"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1023/a:1006338123126", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1023207013", 
              "https://doi.org/10.1023/a:1006338123126"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1054/bjoc.1999.0875", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1023454472", 
              "https://doi.org/10.1054/bjoc.1999.0875"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/s0959-8049(00)00408-1", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1024120358"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/stem.160413", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1025582153"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/stem.160413", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1025582153"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/0065-2571(84)90007-4", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1026371633"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/0065-2571(84)90007-4", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1026371633"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1023/a:1006232830161", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1027264489", 
              "https://doi.org/10.1023/a:1006232830161"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1023/a:1005798224288", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1027515923", 
              "https://doi.org/10.1023/a:1005798224288"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/bjc.1996.259", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1032574059", 
              "https://doi.org/10.1038/bjc.1996.259"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/bjc.1996.259", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1032574059", 
              "https://doi.org/10.1038/bjc.1996.259"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1073/pnas.89.10.4285", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1035465241"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/bf01518520", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1039057223", 
              "https://doi.org/10.1007/bf01518520"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1023/a:1014968415759", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1046446473", 
              "https://doi.org/10.1023/a:1014968415759"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/1097-0142(19860315)57:6<1171::aid-cncr2820570618>3.0.co;2-x", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1046468555"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/ijc.2910630417", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1049248116"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/bf00683195", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1049439558", 
              "https://doi.org/10.1007/bf00683195"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/bf00683195", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1049439558", 
              "https://doi.org/10.1007/bf00683195"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1126/science.270.5241.1491", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1062551722"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1126/science.3798106", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1062621480"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1200/jco.20.3.719", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1064202789"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1210/endo.137.10.8828492", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1064280503"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1210/me.15.8.1344", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1064326974"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1210/mend.15.8.0678", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1064332215"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1074519294", 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1074660242", 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1074721466", 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1077262284", 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1079233841", 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1082404273", 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1082588264", 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/j.1460-2075.1996.tb00571.x", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1082890072"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1083290314", 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1083347332", 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1200/jco.2002.20.3.719", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1083941918"
            ], 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "2004-07", 
        "datePublishedReg": "2004-07-01", 
        "description": "HER2 overexpression has been associated with anti-estrogen resistance in human breast cancer, and it has been suggested that the combined treatment of an anti-HER2 antibody plus tamoxifen has enhanced anti-cancer efficacy in breast cancer. The detailed anti-proliferative interactions between trastuzumab and tamoxifen were analyzed with the isobologram and Chou and Talalay methods, which assess the presence of synergy, addition or antagonism. We used the breast cancer cell lines that are estrogen receptor (ER)-positive and HER2-positive. We also analyzed the molecular changes on the HER2 and (ER) signaling pathways that are induced by trastuzumab plus tamoxifen. In terms of cancer cell proliferation, the simultaneous combination of trastuzumab and tamoxifen on BT-474 cells was more growth inhibitory (44%) than the treatment with trastuzumab (24%) or tamoxifen (31%) alone. Isobologram analysis of simultaneous trastuzumab plus tamoxifen exposure showed, however, that there were antagonistic interactions at an effect level of 30% (IC30). Using Chou and Talalay analysis we also observed antagonistic interactions at lower levels of cell kill, although there were additive effects at highest levels of cell kill. Trastuzumab followed by tamoxifen showed antagonism at all effects levels. Tamoxifen followed by trastuzumab showed antagonism at lower levels of cell kill, and additivity at higher levels of cell kill. Similar interactions were observed using T47D cells. The molecular effects of the combined treatment with trastuzumab plus tamoxifen on the levels of HER2 and ER signaling showed that, with respect to HER2 protein levels, trastuzumab downregulated HER2 by 27%, tamoxifen upregulated HER2 by 40%, and the combination of trastuzumab plus tamoxifen did not induce changes in HER2 respect to control. With respect to HER2 mRNA, trastuzumab upregulated HER2 mRNA to 367%, tamoxifen to 166%, and the combination to 401%. With respect to HER2 phosphorylation, trastuzumab upregulated HER2 phosphorylation to 352%, tamoxifen to 202% and the combination to 633%. Epidermal growth factor receptor levels were not changed by trastuzumab or tamoxifen alone, and were upregulated to 138% by the combination. The protein levels and activity of extracellular recptor kinase were not modified by trastuzumab, tamoxifen or the combination. Finally, estrogen receptor protein and mRNA levels were downregulated to about 50% by trastuzumab, tamoxifen or the combination. Taken together, our results show that in ER-positive breast cancer cells overexpressing HER2, trastuzumab plus tamoxifen have antagonistic interactions when used in combination, and that this antagonism may be related with an increase in HER2 signaling pathways that occurs when tamoxifen is added to trastuzumab.", 
        "genre": "research_article", 
        "id": "sg:pub.10.1023/b:brea.0000032981.20384.c6", 
        "inLanguage": [
          "en"
        ], 
        "isAccessibleForFree": false, 
        "isPartOf": [
          {
            "id": "sg:journal.1092777", 
            "issn": [
              "0167-6806", 
              "1573-7217"
            ], 
            "name": "Breast Cancer Research and Treatment", 
            "type": "Periodical"
          }, 
          {
            "issueNumber": "2", 
            "type": "PublicationIssue"
          }, 
          {
            "type": "PublicationVolume", 
            "volumeNumber": "86"
          }
        ], 
        "name": "Trastuzumab Plus Tamoxifen: Anti-Proliferative and Molecular Interactions in Breast Carcinoma", 
        "pagination": "125-137", 
        "productId": [
          {
            "name": "readcube_id", 
            "type": "PropertyValue", 
            "value": [
              "47b00817027fb62c87d08f0a96414ec3f31cf97fc3366e515c7e8c1dab58fb4d"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "15319565"
            ]
          }, 
          {
            "name": "nlm_unique_id", 
            "type": "PropertyValue", 
            "value": [
              "8111104"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1023/b:brea.0000032981.20384.c6"
            ]
          }, 
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1015046659"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1023/b:brea.0000032981.20384.c6", 
          "https://app.dimensions.ai/details/publication/pub.1015046659"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2019-04-11T01:05", 
        "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
        "sdPublisher": {
          "name": "Springer Nature - SN SciGraph project", 
          "type": "Organization"
        }, 
        "sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000001_0000000264/records_8697_00000504.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "http://link.springer.com/10.1023%2FB%3ABREA.0000032981.20384.c6"
      }
    ]
     

    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.10.1023/b:brea.0000032981.20384.c6'

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

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1023/b:brea.0000032981.20384.c6'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1023/b:brea.0000032981.20384.c6'

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

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1023/b:brea.0000032981.20384.c6'


     

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

    296 TRIPLES      21 PREDICATES      85 URIs      39 LITERALS      27 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1023/b:brea.0000032981.20384.c6 schema:about N0c496ef81bb34569858cbf3e4f63a9ac
    2 N1afda5ec8d11471fa02e4be1dcbb77f8
    3 N1cda880b15484ec9aa0dc220eb5a37b5
    4 N3381e3ee156e4e80a5b79c2730833d13
    5 N3c347ff3a20842b2a0dbd532b3f8cb74
    6 N4331e3bd78db44089e12e1c87d11b859
    7 N5568ce7fb0e44eea9bb9a7216b62b331
    8 N5caf5618d15b4f0f95803ddcda9bbcd9
    9 N60b17f0a5f10410ba70a7d7963f6c719
    10 N61eb47a359ac4b69809307f29ceda987
    11 N673191e264b4407d9e430e89ec8588c1
    12 N860770b2e09f4cec8b6322a8a534d019
    13 N8771be48a9f04a7bb8875adb0c702a74
    14 Na19cc608c3dd4600ad48c4d5eeb6d346
    15 Na805cfc7c5784debad951dcfd35b8667
    16 Nb03b52aefe4a4c4892689bde5afe18c8
    17 Nc335963e445c40f6ad3e5c9614bbbf89
    18 Nd8da8fc1d5e44507b64dd676219474d9
    19 anzsrc-for:11
    20 anzsrc-for:1112
    21 schema:author N49b7d6784c4b4ec59b1887db78b96a6e
    22 schema:citation sg:pub.10.1007/978-1-4615-3500-3_10
    23 sg:pub.10.1007/bf00683195
    24 sg:pub.10.1007/bf01518520
    25 sg:pub.10.1023/a:1005798224288
    26 sg:pub.10.1023/a:1006232830161
    27 sg:pub.10.1023/a:1006338123126
    28 sg:pub.10.1023/a:1014968415759
    29 sg:pub.10.1038/bjc.1996.259
    30 sg:pub.10.1038/sj.onc.1202526
    31 sg:pub.10.1038/sj.onc.1203972
    32 sg:pub.10.1054/bjoc.1999.0875
    33 https://app.dimensions.ai/details/publication/pub.1074519294
    34 https://app.dimensions.ai/details/publication/pub.1074660242
    35 https://app.dimensions.ai/details/publication/pub.1074721466
    36 https://app.dimensions.ai/details/publication/pub.1077262284
    37 https://app.dimensions.ai/details/publication/pub.1079233841
    38 https://app.dimensions.ai/details/publication/pub.1082404273
    39 https://app.dimensions.ai/details/publication/pub.1082588264
    40 https://app.dimensions.ai/details/publication/pub.1083290314
    41 https://app.dimensions.ai/details/publication/pub.1083347332
    42 https://doi.org/10.1002/(sici)1521-1878(199801)20:1<41::aid-bies7>3.0.co;2-v
    43 https://doi.org/10.1002/1097-0142(19860315)57:6<1171::aid-cncr2820570618>3.0.co;2-x
    44 https://doi.org/10.1002/ijc.2910630417
    45 https://doi.org/10.1002/j.1460-2075.1996.tb00571.x
    46 https://doi.org/10.1002/stem.160413
    47 https://doi.org/10.1016/0065-2571(84)90007-4
    48 https://doi.org/10.1016/s0304-419x(97)00032-2
    49 https://doi.org/10.1016/s0959-8049(00)00408-1
    50 https://doi.org/10.1016/s0959-8049(05)80045-0
    51 https://doi.org/10.1073/pnas.87.7.2569
    52 https://doi.org/10.1073/pnas.89.10.4285
    53 https://doi.org/10.1126/science.270.5241.1491
    54 https://doi.org/10.1126/science.3798106
    55 https://doi.org/10.1200/jco.20.3.719
    56 https://doi.org/10.1200/jco.2002.20.3.719
    57 https://doi.org/10.1210/endo.137.10.8828492
    58 https://doi.org/10.1210/me.15.8.1344
    59 https://doi.org/10.1210/mend.15.8.0678
    60 schema:datePublished 2004-07
    61 schema:datePublishedReg 2004-07-01
    62 schema:description HER2 overexpression has been associated with anti-estrogen resistance in human breast cancer, and it has been suggested that the combined treatment of an anti-HER2 antibody plus tamoxifen has enhanced anti-cancer efficacy in breast cancer. The detailed anti-proliferative interactions between trastuzumab and tamoxifen were analyzed with the isobologram and Chou and Talalay methods, which assess the presence of synergy, addition or antagonism. We used the breast cancer cell lines that are estrogen receptor (ER)-positive and HER2-positive. We also analyzed the molecular changes on the HER2 and (ER) signaling pathways that are induced by trastuzumab plus tamoxifen. In terms of cancer cell proliferation, the simultaneous combination of trastuzumab and tamoxifen on BT-474 cells was more growth inhibitory (44%) than the treatment with trastuzumab (24%) or tamoxifen (31%) alone. Isobologram analysis of simultaneous trastuzumab plus tamoxifen exposure showed, however, that there were antagonistic interactions at an effect level of 30% (IC30). Using Chou and Talalay analysis we also observed antagonistic interactions at lower levels of cell kill, although there were additive effects at highest levels of cell kill. Trastuzumab followed by tamoxifen showed antagonism at all effects levels. Tamoxifen followed by trastuzumab showed antagonism at lower levels of cell kill, and additivity at higher levels of cell kill. Similar interactions were observed using T47D cells. The molecular effects of the combined treatment with trastuzumab plus tamoxifen on the levels of HER2 and ER signaling showed that, with respect to HER2 protein levels, trastuzumab downregulated HER2 by 27%, tamoxifen upregulated HER2 by 40%, and the combination of trastuzumab plus tamoxifen did not induce changes in HER2 respect to control. With respect to HER2 mRNA, trastuzumab upregulated HER2 mRNA to 367%, tamoxifen to 166%, and the combination to 401%. With respect to HER2 phosphorylation, trastuzumab upregulated HER2 phosphorylation to 352%, tamoxifen to 202% and the combination to 633%. Epidermal growth factor receptor levels were not changed by trastuzumab or tamoxifen alone, and were upregulated to 138% by the combination. The protein levels and activity of extracellular recptor kinase were not modified by trastuzumab, tamoxifen or the combination. Finally, estrogen receptor protein and mRNA levels were downregulated to about 50% by trastuzumab, tamoxifen or the combination. Taken together, our results show that in ER-positive breast cancer cells overexpressing HER2, trastuzumab plus tamoxifen have antagonistic interactions when used in combination, and that this antagonism may be related with an increase in HER2 signaling pathways that occurs when tamoxifen is added to trastuzumab.
    63 schema:genre research_article
    64 schema:inLanguage en
    65 schema:isAccessibleForFree false
    66 schema:isPartOf Nc5ad4b9aaf4548ad9d251ef0bc9c46f8
    67 Nf2e47c988bce4a109ad73a37f5425881
    68 sg:journal.1092777
    69 schema:name Trastuzumab Plus Tamoxifen: Anti-Proliferative and Molecular Interactions in Breast Carcinoma
    70 schema:pagination 125-137
    71 schema:productId N0544553749c846a984315f250e5bce84
    72 N8c024a56139943c6967a5ac1f9aaedc9
    73 N912581510ec644a5ab77983f945eb528
    74 Na677b51cfcc446359232ad35d8ce696f
    75 Ne7486a2dfce7492e9df6585336a10e34
    76 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015046659
    77 https://doi.org/10.1023/b:brea.0000032981.20384.c6
    78 schema:sdDatePublished 2019-04-11T01:05
    79 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    80 schema:sdPublisher N80b693615b114a99ab91736aeeb6d6c4
    81 schema:url http://link.springer.com/10.1023%2FB%3ABREA.0000032981.20384.c6
    82 sgo:license sg:explorer/license/
    83 sgo:sdDataset articles
    84 rdf:type schema:ScholarlyArticle
    85 N0544553749c846a984315f250e5bce84 schema:name nlm_unique_id
    86 schema:value 8111104
    87 rdf:type schema:PropertyValue
    88 N0c496ef81bb34569858cbf3e4f63a9ac schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    89 schema:name Antineoplastic Agents, Hormonal
    90 rdf:type schema:DefinedTerm
    91 N1afda5ec8d11471fa02e4be1dcbb77f8 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    92 schema:name Antineoplastic Agents
    93 rdf:type schema:DefinedTerm
    94 N1cda880b15484ec9aa0dc220eb5a37b5 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    95 schema:name Antibodies, Monoclonal
    96 rdf:type schema:DefinedTerm
    97 N3381e3ee156e4e80a5b79c2730833d13 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    98 schema:name Genes, erbB-2
    99 rdf:type schema:DefinedTerm
    100 N3c347ff3a20842b2a0dbd532b3f8cb74 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    101 schema:name Trastuzumab
    102 rdf:type schema:DefinedTerm
    103 N4331e3bd78db44089e12e1c87d11b859 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    104 schema:name Tamoxifen
    105 rdf:type schema:DefinedTerm
    106 N49b7d6784c4b4ec59b1887db78b96a6e rdf:first sg:person.01236543376.53
    107 rdf:rest N6c1c9d653a1e4793bb62b37361b2400c
    108 N4a98b4767bef491a90a4a66e1311c185 rdf:first sg:person.01305162525.50
    109 rdf:rest N62fd09bb446f4a7c94c4e55512ff6e28
    110 N5568ce7fb0e44eea9bb9a7216b62b331 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    111 schema:name Female
    112 rdf:type schema:DefinedTerm
    113 N5caf5618d15b4f0f95803ddcda9bbcd9 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    114 schema:name Signal Transduction
    115 rdf:type schema:DefinedTerm
    116 N60b17f0a5f10410ba70a7d7963f6c719 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    117 schema:name Tumor Cells, Cultured
    118 rdf:type schema:DefinedTerm
    119 N61eb47a359ac4b69809307f29ceda987 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    120 schema:name Up-Regulation
    121 rdf:type schema:DefinedTerm
    122 N62fd09bb446f4a7c94c4e55512ff6e28 rdf:first sg:person.01352043071.09
    123 rdf:rest Naea02339c1694e6f88582dddc2f8c1b6
    124 N673191e264b4407d9e430e89ec8588c1 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    125 schema:name Drug Interactions
    126 rdf:type schema:DefinedTerm
    127 N6c1c9d653a1e4793bb62b37361b2400c rdf:first sg:person.01233311174.22
    128 rdf:rest Nd5301ecd70864b7294cd5676404b0194
    129 N80b693615b114a99ab91736aeeb6d6c4 schema:name Springer Nature - SN SciGraph project
    130 rdf:type schema:Organization
    131 N860770b2e09f4cec8b6322a8a534d019 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    132 schema:name Receptors, Estrogen
    133 rdf:type schema:DefinedTerm
    134 N8771be48a9f04a7bb8875adb0c702a74 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    135 schema:name RNA, Messenger
    136 rdf:type schema:DefinedTerm
    137 N8c024a56139943c6967a5ac1f9aaedc9 schema:name readcube_id
    138 schema:value 47b00817027fb62c87d08f0a96414ec3f31cf97fc3366e515c7e8c1dab58fb4d
    139 rdf:type schema:PropertyValue
    140 N912581510ec644a5ab77983f945eb528 schema:name doi
    141 schema:value 10.1023/b:brea.0000032981.20384.c6
    142 rdf:type schema:PropertyValue
    143 Na19cc608c3dd4600ad48c4d5eeb6d346 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    144 schema:name Cell Division
    145 rdf:type schema:DefinedTerm
    146 Na677b51cfcc446359232ad35d8ce696f schema:name pubmed_id
    147 schema:value 15319565
    148 rdf:type schema:PropertyValue
    149 Na805cfc7c5784debad951dcfd35b8667 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    150 schema:name Humans
    151 rdf:type schema:DefinedTerm
    152 Naea02339c1694e6f88582dddc2f8c1b6 rdf:first sg:person.0766655346.71
    153 rdf:rest rdf:nil
    154 Nb03b52aefe4a4c4892689bde5afe18c8 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    155 schema:name Breast Neoplasms
    156 rdf:type schema:DefinedTerm
    157 Nc335963e445c40f6ad3e5c9614bbbf89 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    158 schema:name Receptor, ErbB-2
    159 rdf:type schema:DefinedTerm
    160 Nc5ad4b9aaf4548ad9d251ef0bc9c46f8 schema:issueNumber 2
    161 rdf:type schema:PublicationIssue
    162 Nd5301ecd70864b7294cd5676404b0194 rdf:first sg:person.01163643102.17
    163 rdf:rest N4a98b4767bef491a90a4a66e1311c185
    164 Nd8da8fc1d5e44507b64dd676219474d9 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    165 schema:name Antibodies, Monoclonal, Humanized
    166 rdf:type schema:DefinedTerm
    167 Ne7486a2dfce7492e9df6585336a10e34 schema:name dimensions_id
    168 schema:value pub.1015046659
    169 rdf:type schema:PropertyValue
    170 Nf2e47c988bce4a109ad73a37f5425881 schema:volumeNumber 86
    171 rdf:type schema:PublicationVolume
    172 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
    173 schema:name Medical and Health Sciences
    174 rdf:type schema:DefinedTerm
    175 anzsrc-for:1112 schema:inDefinedTermSet anzsrc-for:
    176 schema:name Oncology and Carcinogenesis
    177 rdf:type schema:DefinedTerm
    178 sg:journal.1092777 schema:issn 0167-6806
    179 1573-7217
    180 schema:name Breast Cancer Research and Treatment
    181 rdf:type schema:Periodical
    182 sg:person.01163643102.17 schema:affiliation https://www.grid.ac/institutes/grid.144756.5
    183 schema:familyName Vázquez-Martín
    184 schema:givenName Alejandro
    185 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01163643102.17
    186 rdf:type schema:Person
    187 sg:person.01233311174.22 schema:affiliation https://www.grid.ac/institutes/grid.144756.5
    188 schema:familyName Abel Menéndez
    189 schema:givenName Javier
    190 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01233311174.22
    191 rdf:type schema:Person
    192 sg:person.01236543376.53 schema:affiliation https://www.grid.ac/institutes/grid.144756.5
    193 schema:familyName Ropero
    194 schema:givenName Santiago
    195 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01236543376.53
    196 rdf:type schema:Person
    197 sg:person.01305162525.50 schema:affiliation https://www.grid.ac/institutes/grid.144756.5
    198 schema:familyName Montero
    199 schema:givenName Sagrario
    200 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01305162525.50
    201 rdf:type schema:Person
    202 sg:person.01352043071.09 schema:affiliation https://www.grid.ac/institutes/grid.144756.5
    203 schema:familyName Cortés-Funes
    204 schema:givenName Hernán
    205 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01352043071.09
    206 rdf:type schema:Person
    207 sg:person.0766655346.71 schema:affiliation https://www.grid.ac/institutes/grid.411295.a
    208 schema:familyName Colomer
    209 schema:givenName Ramon
    210 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0766655346.71
    211 rdf:type schema:Person
    212 sg:pub.10.1007/978-1-4615-3500-3_10 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014349003
    213 https://doi.org/10.1007/978-1-4615-3500-3_10
    214 rdf:type schema:CreativeWork
    215 sg:pub.10.1007/bf00683195 schema:sameAs https://app.dimensions.ai/details/publication/pub.1049439558
    216 https://doi.org/10.1007/bf00683195
    217 rdf:type schema:CreativeWork
    218 sg:pub.10.1007/bf01518520 schema:sameAs https://app.dimensions.ai/details/publication/pub.1039057223
    219 https://doi.org/10.1007/bf01518520
    220 rdf:type schema:CreativeWork
    221 sg:pub.10.1023/a:1005798224288 schema:sameAs https://app.dimensions.ai/details/publication/pub.1027515923
    222 https://doi.org/10.1023/a:1005798224288
    223 rdf:type schema:CreativeWork
    224 sg:pub.10.1023/a:1006232830161 schema:sameAs https://app.dimensions.ai/details/publication/pub.1027264489
    225 https://doi.org/10.1023/a:1006232830161
    226 rdf:type schema:CreativeWork
    227 sg:pub.10.1023/a:1006338123126 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023207013
    228 https://doi.org/10.1023/a:1006338123126
    229 rdf:type schema:CreativeWork
    230 sg:pub.10.1023/a:1014968415759 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046446473
    231 https://doi.org/10.1023/a:1014968415759
    232 rdf:type schema:CreativeWork
    233 sg:pub.10.1038/bjc.1996.259 schema:sameAs https://app.dimensions.ai/details/publication/pub.1032574059
    234 https://doi.org/10.1038/bjc.1996.259
    235 rdf:type schema:CreativeWork
    236 sg:pub.10.1038/sj.onc.1202526 schema:sameAs https://app.dimensions.ai/details/publication/pub.1001624052
    237 https://doi.org/10.1038/sj.onc.1202526
    238 rdf:type schema:CreativeWork
    239 sg:pub.10.1038/sj.onc.1203972 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002227737
    240 https://doi.org/10.1038/sj.onc.1203972
    241 rdf:type schema:CreativeWork
    242 sg:pub.10.1054/bjoc.1999.0875 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023454472
    243 https://doi.org/10.1054/bjoc.1999.0875
    244 rdf:type schema:CreativeWork
    245 https://app.dimensions.ai/details/publication/pub.1074519294 schema:CreativeWork
    246 https://app.dimensions.ai/details/publication/pub.1074660242 schema:CreativeWork
    247 https://app.dimensions.ai/details/publication/pub.1074721466 schema:CreativeWork
    248 https://app.dimensions.ai/details/publication/pub.1077262284 schema:CreativeWork
    249 https://app.dimensions.ai/details/publication/pub.1079233841 schema:CreativeWork
    250 https://app.dimensions.ai/details/publication/pub.1082404273 schema:CreativeWork
    251 https://app.dimensions.ai/details/publication/pub.1082588264 schema:CreativeWork
    252 https://app.dimensions.ai/details/publication/pub.1083290314 schema:CreativeWork
    253 https://app.dimensions.ai/details/publication/pub.1083347332 schema:CreativeWork
    254 https://doi.org/10.1002/(sici)1521-1878(199801)20:1<41::aid-bies7>3.0.co;2-v schema:sameAs https://app.dimensions.ai/details/publication/pub.1013765345
    255 rdf:type schema:CreativeWork
    256 https://doi.org/10.1002/1097-0142(19860315)57:6<1171::aid-cncr2820570618>3.0.co;2-x schema:sameAs https://app.dimensions.ai/details/publication/pub.1046468555
    257 rdf:type schema:CreativeWork
    258 https://doi.org/10.1002/ijc.2910630417 schema:sameAs https://app.dimensions.ai/details/publication/pub.1049248116
    259 rdf:type schema:CreativeWork
    260 https://doi.org/10.1002/j.1460-2075.1996.tb00571.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1082890072
    261 rdf:type schema:CreativeWork
    262 https://doi.org/10.1002/stem.160413 schema:sameAs https://app.dimensions.ai/details/publication/pub.1025582153
    263 rdf:type schema:CreativeWork
    264 https://doi.org/10.1016/0065-2571(84)90007-4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026371633
    265 rdf:type schema:CreativeWork
    266 https://doi.org/10.1016/s0304-419x(97)00032-2 schema:sameAs https://app.dimensions.ai/details/publication/pub.1020171474
    267 rdf:type schema:CreativeWork
    268 https://doi.org/10.1016/s0959-8049(00)00408-1 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024120358
    269 rdf:type schema:CreativeWork
    270 https://doi.org/10.1016/s0959-8049(05)80045-0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010068198
    271 rdf:type schema:CreativeWork
    272 https://doi.org/10.1073/pnas.87.7.2569 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021476395
    273 rdf:type schema:CreativeWork
    274 https://doi.org/10.1073/pnas.89.10.4285 schema:sameAs https://app.dimensions.ai/details/publication/pub.1035465241
    275 rdf:type schema:CreativeWork
    276 https://doi.org/10.1126/science.270.5241.1491 schema:sameAs https://app.dimensions.ai/details/publication/pub.1062551722
    277 rdf:type schema:CreativeWork
    278 https://doi.org/10.1126/science.3798106 schema:sameAs https://app.dimensions.ai/details/publication/pub.1062621480
    279 rdf:type schema:CreativeWork
    280 https://doi.org/10.1200/jco.20.3.719 schema:sameAs https://app.dimensions.ai/details/publication/pub.1064202789
    281 rdf:type schema:CreativeWork
    282 https://doi.org/10.1200/jco.2002.20.3.719 schema:sameAs https://app.dimensions.ai/details/publication/pub.1083941918
    283 rdf:type schema:CreativeWork
    284 https://doi.org/10.1210/endo.137.10.8828492 schema:sameAs https://app.dimensions.ai/details/publication/pub.1064280503
    285 rdf:type schema:CreativeWork
    286 https://doi.org/10.1210/me.15.8.1344 schema:sameAs https://app.dimensions.ai/details/publication/pub.1064326974
    287 rdf:type schema:CreativeWork
    288 https://doi.org/10.1210/mend.15.8.0678 schema:sameAs https://app.dimensions.ai/details/publication/pub.1064332215
    289 rdf:type schema:CreativeWork
    290 https://www.grid.ac/institutes/grid.144756.5 schema:alternateName Hospital Universitario 12 De Octubre
    291 schema:name Division of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain
    292 rdf:type schema:Organization
    293 https://www.grid.ac/institutes/grid.411295.a schema:alternateName Hospital Universitari de Girona Doctor Josep Trueta
    294 schema:name Division of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain
    295 Division of Medical Oncology, Institut Catala Oncologia, Hospital Josep Trueta, Av. França s/n, 17007, Girona, Spain
    296 rdf:type schema:Organization
     




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


    ...