{"id":"https://openalex.org/W2257921150","doi":null,"title":"Combination therapy with AG-490 and interleukin 12 achieves greater antitumor effects than either agent alone.","display_name":"Combination therapy with AG-490 and interleukin 12 achieves greater antitumor effects than either agent alone.","publication_year":2002,"publication_date":"2002-09-01","ids":{"openalex":"https://openalex.org/W2257921150","mag":"2257921150","pmid":"https://pubmed.ncbi.nlm.nih.gov/12481410"},"language":"en","primary_location":{"id":"pmid:12481410","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/12481410","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Molecular cancer therapeutics","raw_type":"Journal Article"},"volume":null,"type":"article","indexed_in":["pubmed"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5087204160","display_name":"Lyudmila G. Burdelya","orcid":"https://orcid.org/0000-0001-8632-9154","observed_orcids":["https://orcid.org/0000-0001-8632-9154"]},"institutions":[{"id":"https://openalex.org/I3019308854","display_name":"Moffitt Cancer Center","ror":"https://ror.org/01xf75524","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I3019308854"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Lyudmila Burdelya","raw_affiliation_strings":["Immunology Program, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Immunology Program, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA","institution_ids":["https://openalex.org/I3019308854"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5065474989","display_name":"Robyn Catlett-Falcone","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Robyn Catlett-Falcone","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5086404962","display_name":"Alexander Levitzki","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Alexander Levitzki","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5043197214","display_name":"Fengdong Cheng","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Fengdong Cheng","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":null,"display_name":"Linda B Mora","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Linda B Mora","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5108222207","display_name":"Eduardo M. Sotomayor","orcid":"https://orcid.org/0009-0009-5081-3855","observed_orcids":["https://orcid.org/0009-0009-5081-3855"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Eduardo Sotomayor","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5076324164","display_name":"Domenico Coppola","orcid":"https://orcid.org/0000-0001-9090-1205","observed_orcids":["https://orcid.org/0000-0001-9090-1205","https://orcid.org/0009-0008-3540-2014"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Domenico Coppola","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5100879188","display_name":"Jiazhi Sun","orcid":"https://orcid.org/0009-0005-1134-548X","observed_orcids":["https://orcid.org/0009-0005-1134-548X"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"JiaZhi Sun","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5103060677","display_name":"Sa\u0131\u0308d M. Sebti","orcid":"https://orcid.org/0000-0001-5163-1038","observed_orcids":["https://orcid.org/0000-0001-5163-1038"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Said Sebti","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5103061547","display_name":"William S. Dalton","orcid":"https://orcid.org/0000-0001-9417-2599","observed_orcids":["https://orcid.org/0000-0001-9417-2599"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"William S Dalton","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5022795218","display_name":"Richard Jove","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Richard Jove","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"last","author":{"id":"https://openalex.org/A5012334511","display_name":"Hua Yu","orcid":"https://orcid.org/0000-0003-0931-1000","observed_orcids":["https://orcid.org/0000-0003-0931-1000"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Hua Yu","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":1.1227,"has_fulltext":false,"cited_by_count":49,"citation_normalized_percentile":{"value":0.77035697,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":88,"max":98},"biblio":{"volume":"1","issue":"11","first_page":"893","last_page":"9"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11503","display_name":"Cytokine Signaling Pathways and Interactions","score":1.0,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T11503","display_name":"Cytokine Signaling Pathways and Interactions","score":1.0,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T11313","display_name":"Immune cells in cancer","score":0.0,"subfield":{"id":"https://openalex.org/subfields/2403","display_name":"Immunology"},"field":{"id":"https://openalex.org/fields/24","display_name":"Immunology and Microbiology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10580","display_name":"Immunotherapy and Immune Responses","score":0.0,"subfield":{"id":"https://openalex.org/subfields/2403","display_name":"Immunology"},"field":{"id":"https://openalex.org/fields/24","display_name":"Immunology and Microbiology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/ag490","display_name":"AG490","score":0.9950000047683716},{"id":"https://openalex.org/keywords/il-12","display_name":"IL-12","score":0.8109999895095825},{"id":"https://openalex.org/keywords/jak-stat-signaling","display_name":"JAK/STAT signaling","score":0.7649999856948853},{"id":"https://openalex.org/keywords/combination-therapy","display_name":"combination therapy","score":0.5910000205039978},{"id":"https://openalex.org/keywords/antitumor-immunity","display_name":"antitumor immunity","score":0.847000002861023},{"id":"https://openalex.org/keywords/macrophage-activation","display_name":"macrophage activation","score":0.878000020980835},{"id":"https://openalex.org/keywords/interferon-gamma","display_name":"interferon-gamma","score":0.9649999737739563},{"id":"https://openalex.org/keywords/multiple-myeloma","display_name":"multiple myeloma","score":0.8420000076293945},{"id":"https://openalex.org/keywords/tumor-cell-apoptosis","display_name":"tumor cell apoptosis","score":0.7789999842643738},{"id":"https://openalex.org/keywords/tyrosine-kinase-inhibitors","display_name":"tyrosine kinase inhibitors","score":0.7390000224113464},{"id":"https://openalex.org/keywords/cytokine-therapy","display_name":"cytokine therapy","score":0.6380000114440918}],"concepts":[{"id":"https://openalex.org/C2778277574","wikidata":"https://www.wikidata.org/wiki/Q665327","display_name":"stat","level":4,"score":0.6725772619247437},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.6399171352386475},{"id":"https://openalex.org/C112392421","wikidata":"https://www.wikidata.org/wiki/Q903451","display_name":"Janus kinase","level":3,"score":0.5853312611579895},{"id":"https://openalex.org/C207001950","wikidata":"https://www.wikidata.org/wiki/Q141124","display_name":"In vivo","level":2,"score":0.5654119253158569},{"id":"https://openalex.org/C2778690821","wikidata":"https://www.wikidata.org/wiki/Q212354","display_name":"Cytokine","level":2,"score":0.5589651465415955},{"id":"https://openalex.org/C157333092","wikidata":"https://www.wikidata.org/wiki/Q902835","display_name":"JAK-STAT signaling pathway","level":4,"score":0.5108889937400818},{"id":"https://openalex.org/C11988809","wikidata":"https://www.wikidata.org/wiki/Q412889","display_name":"Interleukin 6","level":3,"score":0.475035697221756},{"id":"https://openalex.org/C109159458","wikidata":"https://www.wikidata.org/wiki/Q919283","display_name":"Haematopoiesis","level":3,"score":0.4390519857406616},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.42052966356277466},{"id":"https://openalex.org/C171958077","wikidata":"https://www.wikidata.org/wiki/Q419333","display_name":"STAT protein","level":4,"score":0.41544392704963684},{"id":"https://openalex.org/C62478195","wikidata":"https://www.wikidata.org/wiki/Q828130","display_name":"Signal transduction","level":2,"score":0.4052170515060425},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.39269885420799255},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.39029040932655334},{"id":"https://openalex.org/C42362537","wikidata":"https://www.wikidata.org/wiki/Q87099740","display_name":"Tyrosine kinase","level":3,"score":0.38212841749191284},{"id":"https://openalex.org/C2778923194","wikidata":"https://www.wikidata.org/wiki/Q14912019","display_name":"STAT3","level":3,"score":0.380578875541687},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.37480390071868896},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.15782049298286438},{"id":"https://openalex.org/C28328180","wikidata":"https://www.wikidata.org/wiki/Q48196","display_name":"Stem cell","level":2,"score":0.08901411294937134},{"id":"https://openalex.org/C150903083","wikidata":"https://www.wikidata.org/wiki/Q7108","display_name":"Biotechnology","level":1,"score":0.0}],"mesh":[{"descriptor_ui":"D000818","descriptor_name":"Animals","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000970","descriptor_name":"Antineoplastic Agents","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D000971","descriptor_name":"Antineoplastic Combined Chemotherapy Protocols","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D002467","descriptor_name":"Cell Nucleus","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D004268","descriptor_name":"DNA-Binding Proteins","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D005260","descriptor_name":"Female","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D007150","descriptor_name":"Immunohistochemistry","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D007371","descriptor_name":"Interferon-gamma","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D008264","descriptor_name":"Macrophages","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D008807","descriptor_name":"Mice, Inbred BALB C","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D009369","descriptor_name":"Neoplasms","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":true},{"descriptor_ui":"D013154","descriptor_name":"Spleen","qualifier_ui":"Q000166","qualifier_name":"cytology","is_major_topic":false},{"descriptor_ui":"D013997","descriptor_name":"Time Factors","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D014407","descriptor_name":"Tumor Cells, Cultured","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015398","descriptor_name":"Signal Transduction","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015534","descriptor_name":"Trans-Activators","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D016513","descriptor_name":"Mice, SCID","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D017209","descriptor_name":"Apoptosis","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D017737","descriptor_name":"Macrophages, Peritoneal","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D018664","descriptor_name":"Interleukin-12","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D018664","descriptor_name":"Interleukin-12","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D020032","descriptor_name":"Tyrphostins","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D020287","descriptor_name":"In Situ Nick-End Labeling","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D050796","descriptor_name":"STAT3 Transcription Factor","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D051379","descriptor_name":"Mice","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":2,"locations":[{"id":"pmid:12481410","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/12481410","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Molecular cancer therapeutics","raw_type":"Journal Article"},{"id":"mag:2257921150","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/12481410","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":null,"is_accepted":false,"is_published":false,"raw_source_name":"PubMed","raw_type":null}],"best_oa_location":null,"sustainable_development_goals":[{"score":0.9763000011444092,"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being"}],"study_designs":[],"awards":[{"id":"https://openalex.org/G6667071792","display_name":"MOLECULAR ONCOLOGY PROGRAM PROJECT","funder_award_id":"P01CA082533","funder_id":"https://openalex.org/F4320337351","funder_display_name":"National Cancer Institute"},{"id":"https://openalex.org/G7753572251","display_name":"CYTOKINES AS CANCER IMMUNOTHERAPEUTICS","funder_award_id":"R29CA075243","funder_id":"https://openalex.org/F4320337351","funder_display_name":"National Cancer Institute"}],"funders":[{"id":"https://openalex.org/F4320337351","display_name":"National Cancer Institute","ror":"https://ror.org/040gcmg81"}],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":33,"referenced_works":["https://openalex.org/W141701818","https://openalex.org/W159302622","https://openalex.org/W168754456","https://openalex.org/W195552824","https://openalex.org/W1494828357","https://openalex.org/W1530591884","https://openalex.org/W1550156431","https://openalex.org/W1571130313","https://openalex.org/W1777794242","https://openalex.org/W1899668346","https://openalex.org/W1909302889","https://openalex.org/W1982798395","https://openalex.org/W2010925210","https://openalex.org/W2024665305","https://openalex.org/W2027253957","https://openalex.org/W2032674547","https://openalex.org/W2044991100","https://openalex.org/W2051705414","https://openalex.org/W2061857325","https://openalex.org/W2067877107","https://openalex.org/W2074356752","https://openalex.org/W2090297133","https://openalex.org/W2106515248","https://openalex.org/W2118310862","https://openalex.org/W2127048642","https://openalex.org/W2134582745","https://openalex.org/W2138807703","https://openalex.org/W2145106676","https://openalex.org/W2165195703","https://openalex.org/W2330829715","https://openalex.org/W2403474134","https://openalex.org/W4313333712","https://openalex.org/W4313344492"],"related_works":["https://openalex.org/W2061653003","https://openalex.org/W2132437195","https://openalex.org/W1530591884","https://openalex.org/W4409191529","https://openalex.org/W2461161986","https://openalex.org/W2024509030","https://openalex.org/W2061051459","https://openalex.org/W163194484","https://openalex.org/W1966304765","https://openalex.org/W2611353171"],"abstract_inverted_index":{"Constitutive":[0],"activation":[1,127],"of":[2,11,80,99,115],"Janus":[3],"kinases":[4],"(JAKs)":[5],"and":[6,9,23,40,86,101,128,142],"signal":[7,63],"transducers":[8],"activators":[10],"transcription":[12],"(STAT)":[13],"occurs":[14],"at":[15],"very":[16],"high":[17],"frequency":[18],"in":[19,45,90,103,112,151,171],"various":[20],"hematopoietic":[21],"malignancies":[22],"solid":[24],"tumors.":[25],"It":[26],"has":[27],"been":[28,60],"demonstrated":[29],"that":[30,111,137,160],"the":[31,78,96],"tyrosine":[32],"kinase":[33],"inhibitor,":[34],"AG-490,":[35],"selectively":[36],"blocks":[37],"JAK":[38],"activity":[39],"completely":[41],"eliminates":[42],"leukemia":[43],"cells":[44],"a":[46,152],"severe":[47],"combined":[48,138],"immunodeficient":[49],"(SCID)":[50],"mouse":[51],"model.":[52,156],"Because":[53],"many":[54],"cytokines,":[55],"including":[56],"interleukin":[57],"(IL)-12,":[58],"have":[59,94],"shown":[61],"to":[62],"through":[64],"JAK/STAT":[65,161,177],"pathways,":[66],"AG-490":[67,81,116,141],"may":[68],"inhibit":[69,124],"cytokine-based":[70],"cancer":[71],"therapy.":[72],"In":[73],"this":[74],"study,":[75],"we":[76],"evaluated":[77],"effects":[79,146],"on":[82],"IL-12":[83,169],"functional":[84],"signaling":[85],"IL-12-mediated":[87,125],"antitumor":[88,106,145],"response":[89],"vivo.":[91],"Previous":[92],"studies":[93],"established":[95],"critical":[97],"roles":[98],"macrophages":[100],"IFN-gamma":[102,129],"mediating":[104],"IL-12-induced":[105],"effects.":[107],"Our":[108],"results":[109,158],"show":[110],"vivo":[113],"administration":[114],"causes":[117],"tumor":[118,155],"cell":[119],"apoptosis":[120],"but":[121],"does":[122],"not":[123],"macrophage":[126],"production":[130],"by":[131],"lymphocytes.":[132],"Furthermore,":[133],"our":[134],"data":[135],"indicate":[136],"therapy":[139,170],"with":[140,168,175],"IL-12-induces":[143],"greater":[144],"than":[147],"either":[148],"agent":[149],"alone":[150],"murine":[153],"myeloma":[154],"These":[157],"suggest":[159],"inhibitors":[162],"deserve":[163],"further":[164],"investigation":[165],"for":[166],"use":[167],"treating":[172],"human":[173],"cancers":[174],"elevated":[176],"activity.":[178]},"counts_by_year":[{"year":2020,"cited_by_count":1},{"year":2019,"cited_by_count":2},{"year":2018,"cited_by_count":1},{"year":2017,"cited_by_count":2},{"year":2015,"cited_by_count":2},{"year":2014,"cited_by_count":2},{"year":2013,"cited_by_count":5},{"year":2012,"cited_by_count":3}],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2016-06-24T00:00:00"}