Antitumor activity of a phosphorothioate antisense oligodeoxynucleotide targeted against C-raf kinase View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1996-06

AUTHORS

Brett P. Monia, Joseph F. Johnston, Thomas Geiger, Marcel Muller, Doriano Fabbro

ABSTRACT

Substantial evidence exists supporting a direct role for raf kinases in the development and maintenance of certain human malignancies. Here we test the potential of phosphorothioate antisense oligodeoxynucleotides targeted against human C–raf–1 kinase to specifically inhibit C–raf–1 kinase gene expression and tumor progression in cell culture and in vivo, using human tumor xenograft mouse models. Treatment of human tumor cells with appropriate phosphorothioate antisense oligodeoxynucleotides led to specific inhibition of C–raf kinase gene expression in cell culture and in vivo at well–tolerated doses. Moreover, oligodeoxynucleotide treatment resulted in potent antiproliferative effects in cell culture and potent antitumor effects in vivo against a variety of tumor types that were highly consistent with an antisense mechanism of action for these compounds. These studies strongly suggest that antisense inhibitors targeted against C–raf–1 kinase may be of considerable value as antineoplastic agents that display activity against a wide spectrum of tumor types at well–tolerated doses. More... »

PAGES

668-675

Journal

TITLE

Nature Medicine

ISSUE

6

VOLUME

2

Related Patents

  • {1-Methyl-5-[2-(5-Trifluoromethyl-1h-Imidazol-2-Yl)-Pyridin-4-Yloxy]-1h-Benzoimidazol-2-Yl}-(4-Trifluoromethyl-Phenyl)-Amine; Inhibitors Of Kinase/Raf Kinase Activity Associated With Tumorigenesis, Serine/Threonine Kinase Or Receptor Tyrosine Kinase; Cancer; Tumors; Inhibit Mapk Signaling Pathway
  • Cyclic Substituted Fused Pyrrolocarbazoles And Isoindolones
  • Synthesizing Oligonucleotide By Deblocking And Coupling Nucleotides Together, Then Treating With Oxidizing Solution To Convert H-Phosphonate Linkages To Phosphodiester, Phosphorothioate, Phosphoramidate Or Boranophosphate
  • Omega-Carboxyaryl Substituted Diphenyl Ureas As Raf Kinase Inhibitors
  • Raf Kinase Modulator Compounds And Methods Of Use Thereof
  • The Serine/Threonine Kinase Family Includes Members That Regulate Cell Growth, Migration, Differentiation, Gene Expression, Muscle Contraction, Glucose Metabolism, Cellular Protein Synthesis, And Regulation Of The Cell Cycle
  • Nucleotide Sequence That Codes For A Protein That Oxides A Retinoid; For The Treatment Of Cancer; Anticarcinogenic Agents
  • Orally Administering A Chimeric Oligonucleotide That Has Alkylphosphonate , Phosphorodithioate, Alkylphosphonothioate, Phosphoramidite, Phosphate Ester, Carbamate, Carbonate, Phosphate Triester, Acetamidate, And Carboxymethyl Ester Linkages
  • Raf Kinase Modulator Compounds And Methods Of Use Thereof
  • Using Polyamide Nucleic Acid Oligomers To Engender A Biological Response
  • {1-Methyl-5-[2-(5-Trifluoromethyl-1h-Imidazol-2-Yl)-Pyridin-4-Yloxy]-1h-Benzoimidazol-2-Yl}-(4-Trifluoromethyl-Phenyl)-Amine; Inhibitors Of Kinase/ Raf Kinase Activity Associated With Tumorigenesis, Serine/Threonine Kinase Or Receptor Tyrosine Kinase; Cancer; Tumors; Inhibitmapk Signaling Pathway
  • Antibodies To Retinoid Metabolizing Protein
  • Omega-Carboxyaryl Substituted Diphenyl Ureas As Raf Kinase Inhibitors
  • Compositions And Methods For The Modulation Of The Expression Of B7 Protein
  • Ink4c-P18 And Ink4d-P19, Inhibitors Of Cyclin-Dependent Kinases Cdk4 And Cdk6, And Uses Thereof
  • Substituted Benzimidazoles And Methods Of Their Use
  • For Treatment Of Endocrine-Regulated Tumors, For Example, Breast, Prostate, Ovarian And Colon Cancers
  • Methods Of Modulating Serine/Threonine Protein Kinase Function With Azabenzimidazole-Based Compounds
  • Using Polyamide Nucleic Acid Oligomers To Engender A Biological Response
  • Bispecific Oligonucleotide For The Treatment Of Cns Malignancies
  • Compounds, Processes And Intermediates For Synthesis Of Mixed Backbone Oligomeric Compounds
  • Bispecific Antisense Oligonucleotides That Inhibit Igfbp-2 And Igfbp-5 And Methods Of Using Same
  • Chimeric Oligonucleotide Comprising Phosphorothioate Internucleotide Linkage And Complementary To Gene Is Orally Administered
  • Treatment Of Cancer By Inhibition Of Igfbps And Clusterin
  • Aryl Ureas With Angiogenisis Inhibiting Activity
  • Methods Of Modulating Serine/Threonine Protein Kinase Function With Quinazoline-Based Compounds
  • Methods Of Modulating Serine/Thereonine Protein Kinase Function With Quinazoline-Based Compounds
  • Jak/Stat Inhibitors And Mapk/Erk Inhibitors For Rsv Infection
  • Method For Achieving Desired Glial Growth Factor 2 Plasma Levels
  • Kinase Inhibitor; Alzheimer's Disease; Central Nervous System Disorders; Antiinflamamtory Agents; Skin Disorders; Osteoporosis; Atherosclerosis; Restenosis; Thrombosis; Antidiabetic Agents; Viricides; Fungicides
  • Ω-Carboxyl Aryl Substituted Diphenyl Ureas As P38 Kinase Inhibitors
  • Hybrid Oligonucleotides And Uses Thereof
  • Retinoid Metabolizing Protein
  • Modified Protein Kinase A-Specific Oligonucleotides And Methods Of Their Use
  • Method For Achieving Desired Glial Growth Factor 2 Plasma Levels
  • Method For Identifying Accessible Binding Sites On Rna
  • Antisense Nucleic Acids
  • Anticarcinogenic/Antitumor/Antiproliferative Agents And Diagnostic Agents Targeted Against Gene Which Codes For A Protein Kinase Involved In Signal Transduction
  • Antisense Nucleic Acids
  • Bispecific Oligonucleotide For The Treatment Of Cns Malignancies
  • Comprises Nucleotide Sequences Coding Tumor Marker Protein For Treating And Diagnosing Cancer; Gene Expression Inhibition; Antisense Therapy; Antitumor Agents
  • Carbamides Such As N-(3-Tert-Butylphenyl)-N'-(4-(3-(N-Methyl-Carbamoyl)Phenoxy)Phenyl Urea, Used As Enzyme Inhibitors And As Anticarcinogenic Agents
  • Kiaa0175 Inhibitor Is Selected From The Group Consisting Of An Anti-Sense Molecule, A Ribozyme, An Antibody, An Antibody Fragment, A Protein, A Polypeptide And A Small Molecule.
  • Methods Of Modulating Serine/Threonine Protein Kinase Function With Azabenzimidazole-Based Compounds
  • Aryl Urea Compounds In Combination With Other Cytostatic Or Cytotoxic Agents For Treating Human Cancers
  • 3-({4-[1-(2,2-Difluoroethyl)-3-(1h-Pyrrolo[2,3-B]Pyridin-5-Yl)-1h-Pyrazol-4-Yl]Pyrimidin-2-Yl}Amino)Propanenitrile, Used As Serine/Threonine Protein Kinase Inhibitors, For The Treatment Of Disease States Associated With Abnormal Cell Growth Such As Cancer
  • Modulating Apoptosis Or Proliferation Of A Cancer Cell, Comprising Regulating Expression Of Shinc-2
  • Treatment Of Cancer By Inhibition Of Igfbps And Clusterin
  • Methods Of Using Aryl Ureas To Treat Diseases Mediated By The Vegf Induced Signal Transduction Pathway Characterized By Abnormal Angiogenesis Or Hyperpermeability Processes.
  • Antisense Nucleic Acids
  • Antisense Oligonucleotide Modulation Of Raf Gene Expression
  • Method For Achieving Desired Glial Growth Factor 2 Plasma Levels
  • Antisense Nucleic Acids
  • An Oligonucleotide That Encodes A Human Protein Kinases Involved In Signal Transduction Regulating Cell Proliferation; Anticarcinogenic/Antitumor Agents, Diagnosis And Therapy Of Psoriasis, Artherosclerosis, Tissue Grafts
  • Antisense Nucleic Acids
  • Retinoid Metabolizing Protein
  • 2-Indolinone Derivatives As Multi-Target Protein Kinase Inhibitors And Histone Deacetylase Inhibitors
  • Method Of Down-Regulating Gene Expression
  • Chimeric Antisense Oligonucleotides Of Arabinofuranose Analogue And Deoxyribose Nucleotides
  • Oligoribonucleotides And Ribonucleases For Cleaving Rna
  • Antisense Nucleic Acids
  • Bispecific Antisense Oligonucleotides That Inhibit Igfbp-2 And Igfbp-5 And Methods Of Using Same
  • Aryl Ureas With Angiogenesis Inhibiting Activity
  • Method For Identifying Accessible Binding Sites On Rna
  • Antisense Oligonucleotide Modulation Of Raf Gene Expression
  • Naphthamide Derivatives As Multi-Target Protein Kinase Inhibitors And Histone Deacetylase Inhibitors
  • Hybridization And Rnace Activation In A Cell With Oligonucleotides
  • Agents For The Regulation Of Protein Kinase
  • Treatment Of Cancer By Inhibition Of Igfbp's And Clusterin
  • Pyridine, Quinoline, And Isoquinoline N-Oxides As Kinase Inhibitors
  • Treatment Of Cancer By Inhibition Of Igfbps And Clusterin
  • Preventing And Treating Serine/Threonine Protein Kinase-Related Abnormal Conditions In Mammals Associated With An Aberration In A Signal Transduction Pathway Such As Cancer Or A Fibrotic Disorder
  • Retinoid Metabolizing Protein
  • For Therapy Of Autoimmune Disease, Inflammatory Disease, For Inhibiting Allograft Rejection
  • Bispecific Antisense Oligonucleotides That Inhibit Igfbp-2 And Igfbp-5 And Methods Of Using Same
  • Treatment Of Cancer By Inhibition Of Igfbps And Clusterin
  • Methods For The Treatment Of Cancer
  • Substituted Pyrimidine Derivatives Useful In The Treatment Of Cancer And Other Disorders
  • Oligonucleotide Compositions And Methods For The Modulation Of The Expression Of B7 Protein
  • Modulate Nucleic Acid Activation
  • Modified Protein Kinase A-Specific Oligonucleotides And Methods Of Their Use
  • Oligonucleotides Which Contain Region(S) Of 2'-Modified Nucleosides Connected By Alternating Phosphodiester And Phosphorothioate Linkages; Use As Antisense Agents, Assaying A Nucleic Acid; Nuclease Resistant
  • Such As {1-Methyl-5-[2-(5-Trifluoromethyl-1h-Imidazol-2-Yl)-Pyridin-4-Yloxy]-1h-Benzoimidazol-2-Yl}-(4-Trifluoromethyl-Phenyl)-Amine Via Reduction, Desulfurization; For Treating Kinase Mediated Disorders
  • Diaryl Ureas For Diseases Mediated By Pdgfr
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nm0696-668

    DOI

    http://dx.doi.org/10.1038/nm0696-668

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1039646445

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/8640558


    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": "Animals", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Antineoplastic Agents", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Base Sequence", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Carcinoma", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cell Division", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Dose-Response Relationship, Drug", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Gene Expression Regulation, Neoplastic", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Humans", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Lung Neoplasms", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Mice", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Mice, Inbred BALB C", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Molecular Sequence Data", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Neoplasms, Experimental", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Oligodeoxyribonucleotides, Antisense", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Oligonucleotides, Antisense", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Protein Serine-Threonine Kinases", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Proto-Oncogene Proteins", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Proto-Oncogene Proteins c-raf", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "RNA, Messenger", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Thionucleotides", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Transplantation, Heterologous", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Tumor Cells, Cultured", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "alternateName": "Department of Molecular Pharmacology, Isis Pharmaceuticals, 2280 Faraday Avenue, 92008, Carlsbad, California, USA", 
              "id": "http://www.grid.ac/institutes/grid.282569.2", 
              "name": [
                "Department of Molecular Pharmacology, Isis Pharmaceuticals, 2280 Faraday Avenue, 92008, Carlsbad, California, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Monia", 
            "givenName": "Brett P.", 
            "id": "sg:person.01344750652.90", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01344750652.90"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Molecular Pharmacology, Isis Pharmaceuticals, 2280 Faraday Avenue, 92008, Carlsbad, California, USA", 
              "id": "http://www.grid.ac/institutes/grid.282569.2", 
              "name": [
                "Department of Molecular Pharmacology, Isis Pharmaceuticals, 2280 Faraday Avenue, 92008, Carlsbad, California, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Johnston", 
            "givenName": "Joseph F.", 
            "id": "sg:person.01016273314.94", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01016273314.94"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Oncology, Ciba-Geigy Limited, CH-4002, Basel, Switzerland", 
              "id": "http://www.grid.ac/institutes/grid.419481.1", 
              "name": [
                "Department of Oncology, Ciba-Geigy Limited, CH-4002, Basel, Switzerland"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Geiger", 
            "givenName": "Thomas", 
            "id": "sg:person.0676041204.53", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0676041204.53"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Oncology, Ciba-Geigy Limited, CH-4002, Basel, Switzerland", 
              "id": "http://www.grid.ac/institutes/grid.419481.1", 
              "name": [
                "Department of Oncology, Ciba-Geigy Limited, CH-4002, Basel, Switzerland"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Muller", 
            "givenName": "Marcel", 
            "id": "sg:person.012524430742.96", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012524430742.96"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Department of Oncology, Ciba-Geigy Limited, CH-4002, Basel, Switzerland", 
              "id": "http://www.grid.ac/institutes/grid.419481.1", 
              "name": [
                "Department of Oncology, Ciba-Geigy Limited, CH-4002, Basel, Switzerland"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Fabbro", 
            "givenName": "Doriano", 
            "id": "sg:person.01342570171.22", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01342570171.22"
            ], 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "sg:pub.10.1038/nm1195-1119", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1052115793", 
              "https://doi.org/10.1038/nm1195-1119"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nm0695-541", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1012035936", 
              "https://doi.org/10.1038/nm0695-541"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/978-3-642-72624-8_97", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1024254887", 
              "https://doi.org/10.1007/978-3-642-72624-8_97"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nm1195-1116", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1022849626", 
              "https://doi.org/10.1038/nm1195-1116"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/364352a0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1051824867", 
              "https://doi.org/10.1038/364352a0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/364308a0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1021693984", 
              "https://doi.org/10.1038/364308a0"
            ], 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "1996-06", 
        "datePublishedReg": "1996-06-01", 
        "description": "Substantial evidence exists supporting a direct role for raf kinases in the development and maintenance of certain human malignancies. Here we test the potential of phosphorothioate antisense oligodeoxynucleotides targeted against human C\u2013raf\u20131 kinase to specifically inhibit C\u2013raf\u20131 kinase gene expression and tumor progression in cell culture and in vivo, using human tumor xenograft mouse models. Treatment of human tumor cells with appropriate phosphorothioate antisense oligodeoxynucleotides led to specific inhibition of C\u2013raf kinase gene expression in cell culture and in vivo at well\u2013tolerated doses. Moreover, oligodeoxynucleotide treatment resulted in potent antiproliferative effects in cell culture and potent antitumor effects in vivo against a variety of tumor types that were highly consistent with an antisense mechanism of action for these compounds. These studies strongly suggest that antisense inhibitors targeted against C\u2013raf\u20131 kinase may be of considerable value as antineoplastic agents that display activity against a wide spectrum of tumor types at well\u2013tolerated doses.", 
        "genre": "article", 
        "id": "sg:pub.10.1038/nm0696-668", 
        "isAccessibleForFree": false, 
        "isPartOf": [
          {
            "id": "sg:journal.1113716", 
            "issn": [
              "1078-8956", 
              "1546-170X"
            ], 
            "name": "Nature Medicine", 
            "publisher": "Springer Nature", 
            "type": "Periodical"
          }, 
          {
            "issueNumber": "6", 
            "type": "PublicationIssue"
          }, 
          {
            "type": "PublicationVolume", 
            "volumeNumber": "2"
          }
        ], 
        "keywords": [
          "phosphorothioate antisense oligodeoxynucleotides", 
          "tumor types", 
          "antisense oligodeoxynucleotides", 
          "human tumor xenograft mouse model", 
          "tumor xenograft mouse model", 
          "potent antitumor effects", 
          "xenograft mouse model", 
          "potent antiproliferative effects", 
          "cell cultures", 
          "certain human malignancies", 
          "kinase gene expression", 
          "human tumor cells", 
          "mouse model", 
          "antitumor effects", 
          "c-Raf", 
          "tumor progression", 
          "antineoplastic agents", 
          "human malignancies", 
          "antiproliferative effects", 
          "tumor cells", 
          "oligodeoxynucleotide treatment", 
          "gene expression", 
          "antitumor activity", 
          "specific inhibition", 
          "antisense inhibitor", 
          "substantial evidence", 
          "doses", 
          "vivo", 
          "c-Raf kinase", 
          "treatment", 
          "direct role", 
          "wide spectrum", 
          "oligodeoxynucleotides", 
          "kinase", 
          "Raf kinase", 
          "malignancy", 
          "expression", 
          "progression", 
          "antisense mechanism", 
          "inhibitors", 
          "activity", 
          "inhibition", 
          "culture", 
          "effect", 
          "cells", 
          "considerable value", 
          "agents", 
          "evidence", 
          "study", 
          "role", 
          "action", 
          "human c-raf", 
          "types", 
          "maintenance", 
          "mechanism", 
          "development", 
          "potential", 
          "variety", 
          "compounds", 
          "values", 
          "model", 
          "spectra"
        ], 
        "name": "Antitumor activity of a phosphorothioate antisense oligodeoxynucleotide targeted against C-raf kinase", 
        "pagination": "668-675", 
        "productId": [
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1039646445"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1038/nm0696-668"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "8640558"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1038/nm0696-668", 
          "https://app.dimensions.ai/details/publication/pub.1039646445"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2022-11-24T20:48", 
        "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
        "sdPublisher": {
          "name": "Springer Nature - SN SciGraph project", 
          "type": "Organization"
        }, 
        "sdSource": "s3://com-springernature-scigraph/baseset/20221124/entities/gbq_results/article/article_263.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "https://doi.org/10.1038/nm0696-668"
      }
    ]
     

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

    HOW TO GET THIS DATA PROGRAMMATICALLY:

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

    curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/nm0696-668'

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

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/nm0696-668'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/nm0696-668'

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

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/nm0696-668'


     

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

    266 TRIPLES      21 PREDICATES      116 URIs      102 LITERALS      29 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1038/nm0696-668 schema:about N05363305d1d74bcfb28c04b383c480b4
    2 N0a60d6e362844f9e9b18729e2380255d
    3 N16344cecb9b348439ca8a3e614c59167
    4 N18593d46764d41c382e2932de56f8b2f
    5 N1a2f1cd9744b4620bca9a1ce88858a87
    6 N29ccedbc72d3438da522449ceded6542
    7 N4e719aca6f974d53a7830435748e84b7
    8 N4f307d7f4ed34559957a229f8cb0fb15
    9 N5444c45298b44b1fa3c359c6ceae356f
    10 N71bbb1126cb64f12bb9507ead2e691d7
    11 N8e066e11794e4f83b267063763a98868
    12 N9c5bd246a4e44bbc887cfe109268791e
    13 N9ef95822a9064d619b3b1944f074bae2
    14 Nbcd1c658a65d493a90a735719ff26815
    15 Nbcf8c78e137d443e999ec6ea87cb0206
    16 Nd0a8208529fe4d7e8eda4e4aabddcc77
    17 Nd7c8103697c6410fb565f17be655d666
    18 Ne40571d5425f4a99b33c57c12fef8b31
    19 Nf5a1f7a8dd7c45319c819ba708020b1a
    20 Nf5c5cf68161d40e18894ebbdc74ddd2a
    21 Nf67f438c11a541428001951e4ec9341c
    22 Nff13c68e6ee94ccd9f2c139c37681ce0
    23 anzsrc-for:11
    24 anzsrc-for:1112
    25 schema:author N1f3cd51872c444868577ed15ff70c55d
    26 schema:citation sg:pub.10.1007/978-3-642-72624-8_97
    27 sg:pub.10.1038/364308a0
    28 sg:pub.10.1038/364352a0
    29 sg:pub.10.1038/nm0695-541
    30 sg:pub.10.1038/nm1195-1116
    31 sg:pub.10.1038/nm1195-1119
    32 schema:datePublished 1996-06
    33 schema:datePublishedReg 1996-06-01
    34 schema:description Substantial evidence exists supporting a direct role for raf kinases in the development and maintenance of certain human malignancies. Here we test the potential of phosphorothioate antisense oligodeoxynucleotides targeted against human C–raf–1 kinase to specifically inhibit C–raf–1 kinase gene expression and tumor progression in cell culture and in vivo, using human tumor xenograft mouse models. Treatment of human tumor cells with appropriate phosphorothioate antisense oligodeoxynucleotides led to specific inhibition of C–raf kinase gene expression in cell culture and in vivo at well–tolerated doses. Moreover, oligodeoxynucleotide treatment resulted in potent antiproliferative effects in cell culture and potent antitumor effects in vivo against a variety of tumor types that were highly consistent with an antisense mechanism of action for these compounds. These studies strongly suggest that antisense inhibitors targeted against C–raf–1 kinase may be of considerable value as antineoplastic agents that display activity against a wide spectrum of tumor types at well–tolerated doses.
    35 schema:genre article
    36 schema:isAccessibleForFree false
    37 schema:isPartOf N4c7aee7c90424ec08942aacfd9156c84
    38 Nef8dd3218dc344e4b2273396451e6d84
    39 sg:journal.1113716
    40 schema:keywords Raf kinase
    41 action
    42 activity
    43 agents
    44 antineoplastic agents
    45 antiproliferative effects
    46 antisense inhibitor
    47 antisense mechanism
    48 antisense oligodeoxynucleotides
    49 antitumor activity
    50 antitumor effects
    51 c-Raf
    52 c-Raf kinase
    53 cell cultures
    54 cells
    55 certain human malignancies
    56 compounds
    57 considerable value
    58 culture
    59 development
    60 direct role
    61 doses
    62 effect
    63 evidence
    64 expression
    65 gene expression
    66 human c-raf
    67 human malignancies
    68 human tumor cells
    69 human tumor xenograft mouse model
    70 inhibition
    71 inhibitors
    72 kinase
    73 kinase gene expression
    74 maintenance
    75 malignancy
    76 mechanism
    77 model
    78 mouse model
    79 oligodeoxynucleotide treatment
    80 oligodeoxynucleotides
    81 phosphorothioate antisense oligodeoxynucleotides
    82 potent antiproliferative effects
    83 potent antitumor effects
    84 potential
    85 progression
    86 role
    87 specific inhibition
    88 spectra
    89 study
    90 substantial evidence
    91 treatment
    92 tumor cells
    93 tumor progression
    94 tumor types
    95 tumor xenograft mouse model
    96 types
    97 values
    98 variety
    99 vivo
    100 wide spectrum
    101 xenograft mouse model
    102 schema:name Antitumor activity of a phosphorothioate antisense oligodeoxynucleotide targeted against C-raf kinase
    103 schema:pagination 668-675
    104 schema:productId N33b5ee48ae1c4118998f649c700d60f9
    105 Nbb839a52f2264b1bb3ca271e50cff8df
    106 Nd58b5d0636d64fe1bd2ee24e206b6eb2
    107 schema:sameAs https://app.dimensions.ai/details/publication/pub.1039646445
    108 https://doi.org/10.1038/nm0696-668
    109 schema:sdDatePublished 2022-11-24T20:48
    110 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    111 schema:sdPublisher N7c38775d54c24eecb332d834e792535f
    112 schema:url https://doi.org/10.1038/nm0696-668
    113 sgo:license sg:explorer/license/
    114 sgo:sdDataset articles
    115 rdf:type schema:ScholarlyArticle
    116 N05363305d1d74bcfb28c04b383c480b4 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    117 schema:name Lung Neoplasms
    118 rdf:type schema:DefinedTerm
    119 N0a60d6e362844f9e9b18729e2380255d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    120 schema:name Oligonucleotides, Antisense
    121 rdf:type schema:DefinedTerm
    122 N16344cecb9b348439ca8a3e614c59167 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    123 schema:name Antineoplastic Agents
    124 rdf:type schema:DefinedTerm
    125 N18593d46764d41c382e2932de56f8b2f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    126 schema:name Proto-Oncogene Proteins c-raf
    127 rdf:type schema:DefinedTerm
    128 N1a2f1cd9744b4620bca9a1ce88858a87 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    129 schema:name Molecular Sequence Data
    130 rdf:type schema:DefinedTerm
    131 N1f3cd51872c444868577ed15ff70c55d rdf:first sg:person.01344750652.90
    132 rdf:rest N5228c95ba1c74c488915d1ac91022cac
    133 N29ccedbc72d3438da522449ceded6542 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    134 schema:name Humans
    135 rdf:type schema:DefinedTerm
    136 N317bdb004c1f455f8e715a7dd1b1e9bd rdf:first sg:person.0676041204.53
    137 rdf:rest Nc24fcc3aef77461db4074b77d6f9c1c1
    138 N33b5ee48ae1c4118998f649c700d60f9 schema:name doi
    139 schema:value 10.1038/nm0696-668
    140 rdf:type schema:PropertyValue
    141 N4c7aee7c90424ec08942aacfd9156c84 schema:issueNumber 6
    142 rdf:type schema:PublicationIssue
    143 N4e719aca6f974d53a7830435748e84b7 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    144 schema:name Cell Division
    145 rdf:type schema:DefinedTerm
    146 N4f307d7f4ed34559957a229f8cb0fb15 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    147 schema:name Carcinoma
    148 rdf:type schema:DefinedTerm
    149 N5228c95ba1c74c488915d1ac91022cac rdf:first sg:person.01016273314.94
    150 rdf:rest N317bdb004c1f455f8e715a7dd1b1e9bd
    151 N5444c45298b44b1fa3c359c6ceae356f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    152 schema:name Mice, Inbred BALB C
    153 rdf:type schema:DefinedTerm
    154 N71bbb1126cb64f12bb9507ead2e691d7 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    155 schema:name Mice
    156 rdf:type schema:DefinedTerm
    157 N7c38775d54c24eecb332d834e792535f schema:name Springer Nature - SN SciGraph project
    158 rdf:type schema:Organization
    159 N8e066e11794e4f83b267063763a98868 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    160 schema:name Transplantation, Heterologous
    161 rdf:type schema:DefinedTerm
    162 N9c5bd246a4e44bbc887cfe109268791e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    163 schema:name Dose-Response Relationship, Drug
    164 rdf:type schema:DefinedTerm
    165 N9ef95822a9064d619b3b1944f074bae2 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    166 schema:name Neoplasms, Experimental
    167 rdf:type schema:DefinedTerm
    168 Nb2ebfdc4757a451c82ac182d3fb6aebd rdf:first sg:person.01342570171.22
    169 rdf:rest rdf:nil
    170 Nbb839a52f2264b1bb3ca271e50cff8df schema:name dimensions_id
    171 schema:value pub.1039646445
    172 rdf:type schema:PropertyValue
    173 Nbcd1c658a65d493a90a735719ff26815 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    174 schema:name Protein Serine-Threonine Kinases
    175 rdf:type schema:DefinedTerm
    176 Nbcf8c78e137d443e999ec6ea87cb0206 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    177 schema:name Thionucleotides
    178 rdf:type schema:DefinedTerm
    179 Nc24fcc3aef77461db4074b77d6f9c1c1 rdf:first sg:person.012524430742.96
    180 rdf:rest Nb2ebfdc4757a451c82ac182d3fb6aebd
    181 Nd0a8208529fe4d7e8eda4e4aabddcc77 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    182 schema:name Oligodeoxyribonucleotides, Antisense
    183 rdf:type schema:DefinedTerm
    184 Nd58b5d0636d64fe1bd2ee24e206b6eb2 schema:name pubmed_id
    185 schema:value 8640558
    186 rdf:type schema:PropertyValue
    187 Nd7c8103697c6410fb565f17be655d666 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    188 schema:name RNA, Messenger
    189 rdf:type schema:DefinedTerm
    190 Ne40571d5425f4a99b33c57c12fef8b31 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    191 schema:name Animals
    192 rdf:type schema:DefinedTerm
    193 Nef8dd3218dc344e4b2273396451e6d84 schema:volumeNumber 2
    194 rdf:type schema:PublicationVolume
    195 Nf5a1f7a8dd7c45319c819ba708020b1a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    196 schema:name Base Sequence
    197 rdf:type schema:DefinedTerm
    198 Nf5c5cf68161d40e18894ebbdc74ddd2a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    199 schema:name Proto-Oncogene Proteins
    200 rdf:type schema:DefinedTerm
    201 Nf67f438c11a541428001951e4ec9341c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    202 schema:name Gene Expression Regulation, Neoplastic
    203 rdf:type schema:DefinedTerm
    204 Nff13c68e6ee94ccd9f2c139c37681ce0 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    205 schema:name Tumor Cells, Cultured
    206 rdf:type schema:DefinedTerm
    207 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
    208 schema:name Medical and Health Sciences
    209 rdf:type schema:DefinedTerm
    210 anzsrc-for:1112 schema:inDefinedTermSet anzsrc-for:
    211 schema:name Oncology and Carcinogenesis
    212 rdf:type schema:DefinedTerm
    213 sg:journal.1113716 schema:issn 1078-8956
    214 1546-170X
    215 schema:name Nature Medicine
    216 schema:publisher Springer Nature
    217 rdf:type schema:Periodical
    218 sg:person.01016273314.94 schema:affiliation grid-institutes:grid.282569.2
    219 schema:familyName Johnston
    220 schema:givenName Joseph F.
    221 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01016273314.94
    222 rdf:type schema:Person
    223 sg:person.012524430742.96 schema:affiliation grid-institutes:grid.419481.1
    224 schema:familyName Muller
    225 schema:givenName Marcel
    226 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012524430742.96
    227 rdf:type schema:Person
    228 sg:person.01342570171.22 schema:affiliation grid-institutes:grid.419481.1
    229 schema:familyName Fabbro
    230 schema:givenName Doriano
    231 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01342570171.22
    232 rdf:type schema:Person
    233 sg:person.01344750652.90 schema:affiliation grid-institutes:grid.282569.2
    234 schema:familyName Monia
    235 schema:givenName Brett P.
    236 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01344750652.90
    237 rdf:type schema:Person
    238 sg:person.0676041204.53 schema:affiliation grid-institutes:grid.419481.1
    239 schema:familyName Geiger
    240 schema:givenName Thomas
    241 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0676041204.53
    242 rdf:type schema:Person
    243 sg:pub.10.1007/978-3-642-72624-8_97 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024254887
    244 https://doi.org/10.1007/978-3-642-72624-8_97
    245 rdf:type schema:CreativeWork
    246 sg:pub.10.1038/364308a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021693984
    247 https://doi.org/10.1038/364308a0
    248 rdf:type schema:CreativeWork
    249 sg:pub.10.1038/364352a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1051824867
    250 https://doi.org/10.1038/364352a0
    251 rdf:type schema:CreativeWork
    252 sg:pub.10.1038/nm0695-541 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012035936
    253 https://doi.org/10.1038/nm0695-541
    254 rdf:type schema:CreativeWork
    255 sg:pub.10.1038/nm1195-1116 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022849626
    256 https://doi.org/10.1038/nm1195-1116
    257 rdf:type schema:CreativeWork
    258 sg:pub.10.1038/nm1195-1119 schema:sameAs https://app.dimensions.ai/details/publication/pub.1052115793
    259 https://doi.org/10.1038/nm1195-1119
    260 rdf:type schema:CreativeWork
    261 grid-institutes:grid.282569.2 schema:alternateName Department of Molecular Pharmacology, Isis Pharmaceuticals, 2280 Faraday Avenue, 92008, Carlsbad, California, USA
    262 schema:name Department of Molecular Pharmacology, Isis Pharmaceuticals, 2280 Faraday Avenue, 92008, Carlsbad, California, USA
    263 rdf:type schema:Organization
    264 grid-institutes:grid.419481.1 schema:alternateName Department of Oncology, Ciba-Geigy Limited, CH-4002, Basel, Switzerland
    265 schema:name Department of Oncology, Ciba-Geigy Limited, CH-4002, Basel, Switzerland
    266 rdf:type schema:Organization
     




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


    ...