{"id":"https://openalex.org/W2053793072","doi":"https://doi.org/10.1158/1538-7445.am2011-4507","title":"Abstract 4507: Small molecule inhibitor of MDM2 induces p53-dependent HMGB1 secretion followed by apoptosis in cancer cells and incomplete senescence in normal fibroblasts","display_name":"Abstract 4507: Small molecule inhibitor of MDM2 induces p53-dependent HMGB1 secretion followed by apoptosis in cancer cells and incomplete senescence in normal fibroblasts","publication_year":2011,"publication_date":"2011-04-01","ids":{"openalex":"https://openalex.org/W2053793072","doi":"https://doi.org/10.1158/1538-7445.am2011-4507","mag":"2053793072"},"language":"en","primary_location":{"id":"doi:10.1158/1538-7445.am2011-4507","doi":"https://doi.org/10.1158/1538-7445.am2011-4507","is_oa":false,"landing_page_url":"https://doi.org/10.1158/1538-7445.am2011-4507","pdf_url":null,"source":{"id":"https://openalex.org/S168522863","display_name":"Cancer Research","issn_l":"0008-5472","issn":["0008-5472","1538-7445"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","doyens","jufo-3","ki-jl-3","medline","norway-2"],"host_organization":"https://openalex.org/P4310320273","host_organization_name":"American Association for Cancer Research","host_organization_lineage":["https://openalex.org/P4310320273"],"host_organization_lineage_names":["American Association for Cancer Research"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Cancer Research","raw_type":"journal-article"},"volume":null,"type":"conference-abstract","indexed_in":["crossref"],"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/A5108833365","display_name":"Gary K. Scott","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1337826666","display_name":"Buck Institute for Research on Aging","ror":"https://ror.org/050sv4x28","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I1337826666"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Gary K. Scott","raw_affiliation_strings":["1Buck Inst. for Age Research, Novato, CA","1Buck Institute for Age Research, Novato, CA;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Buck Inst. for Age Research, Novato, CA","institution_ids":["https://openalex.org/I1337826666"]},{"raw_affiliation_string":"1Buck Institute for Age Research, Novato, CA;","institution_ids":["https://openalex.org/I1337826666"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5053220038","display_name":"Albert R. Davalos","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1337826666","display_name":"Buck Institute for Research on Aging","ror":"https://ror.org/050sv4x28","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I1337826666"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Albert Davalos","raw_affiliation_strings":["1Buck Inst. for Age Research, Novato, CA","1Buck Institute for Age Research, Novato, CA;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Buck Inst. for Age Research, Novato, CA","institution_ids":["https://openalex.org/I1337826666"]},{"raw_affiliation_string":"1Buck Institute for Age Research, Novato, CA;","institution_ids":["https://openalex.org/I1337826666"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5111489806","display_name":"Arturo V. Orjalo","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1337826666","display_name":"Buck Institute for Research on Aging","ror":"https://ror.org/050sv4x28","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I1337826666"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Arturo Orjalo","raw_affiliation_strings":["1Buck Inst. for Age Research, Novato, CA","1Buck Institute for Age Research, Novato, CA;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Buck Inst. for Age Research, Novato, CA","institution_ids":["https://openalex.org/I1337826666"]},{"raw_affiliation_string":"1Buck Institute for Age Research, Novato, CA;","institution_ids":["https://openalex.org/I1337826666"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5083023775","display_name":"Rachel Puckett","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1337826666","display_name":"Buck Institute for Research on Aging","ror":"https://ror.org/050sv4x28","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I1337826666"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Rachel Puckett","raw_affiliation_strings":["1Buck Inst. for Age Research, Novato, CA","1Buck Institute for Age Research, Novato, CA;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Buck Inst. for Age Research, Novato, CA","institution_ids":["https://openalex.org/I1337826666"]},{"raw_affiliation_string":"1Buck Institute for Age Research, Novato, CA;","institution_ids":["https://openalex.org/I1337826666"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5045772780","display_name":"Jason M. Held","orcid":"https://orcid.org/0000-0001-8024-2736","observed_orcids":["https://orcid.org/0000-0001-8024-2736"]},"institutions":[{"id":"https://openalex.org/I1337826666","display_name":"Buck Institute for Research on Aging","ror":"https://ror.org/050sv4x28","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I1337826666"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Jason Held","raw_affiliation_strings":["1Buck Inst. for Age Research, Novato, CA","1Buck Institute for Age Research, Novato, CA;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Buck Inst. for Age Research, Novato, CA","institution_ids":["https://openalex.org/I1337826666"]},{"raw_affiliation_string":"1Buck Institute for Age Research, Novato, CA;","institution_ids":["https://openalex.org/I1337826666"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5062190609","display_name":"Christina S. F. Yau","orcid":"https://orcid.org/0000-0002-1937-0859","observed_orcids":["https://orcid.org/0000-0002-1937-0859"]},"institutions":[{"id":"https://openalex.org/I1337826666","display_name":"Buck Institute for Research on Aging","ror":"https://ror.org/050sv4x28","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I1337826666"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Christina Yau","raw_affiliation_strings":["1Buck Inst. for Age Research, Novato, CA","1Buck Institute for Age Research, Novato, CA;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Buck Inst. for Age Research, Novato, CA","institution_ids":["https://openalex.org/I1337826666"]},{"raw_affiliation_string":"1Buck Institute for Age Research, Novato, CA;","institution_ids":["https://openalex.org/I1337826666"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5001970748","display_name":"Judith Campisi","orcid":"https://orcid.org/0000-0001-6858-9462","observed_orcids":["https://orcid.org/0000-0001-6858-9462"]},"institutions":[{"id":"https://openalex.org/I1337826666","display_name":"Buck Institute for Research on Aging","ror":"https://ror.org/050sv4x28","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I1337826666"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Judith Campisi","raw_affiliation_strings":["1Buck Inst. for Age Research, Novato, CA","1Buck Institute for Age Research, Novato, CA;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Buck Inst. for Age Research, Novato, CA","institution_ids":["https://openalex.org/I1337826666"]},{"raw_affiliation_string":"1Buck Institute for Age Research, Novato, CA;","institution_ids":["https://openalex.org/I1337826666"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5013069844","display_name":"Christopher C. Benz","orcid":"https://orcid.org/0000-0001-5479-4641","observed_orcids":["https://orcid.org/0000-0001-5479-4641"]},"institutions":[{"id":"https://openalex.org/I1337826666","display_name":"Buck Institute for Research on Aging","ror":"https://ror.org/050sv4x28","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I1337826666"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Christopher C. Benz","raw_affiliation_strings":["1Buck Inst. for Age Research, Novato, CA","1Buck Institute for Age Research, Novato, CA;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Buck Inst. for Age Research, Novato, CA","institution_ids":["https://openalex.org/I1337826666"]},{"raw_affiliation_string":"1Buck Institute for Age Research, Novato, CA;","institution_ids":["https://openalex.org/I1337826666"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":[],"corresponding_institution_ids":["https://openalex.org/I1337826666"],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":"71","issue":"8_Supplement","first_page":"4507","last_page":"4507"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10583","display_name":"Cancer-related Molecular Pathways","score":0.9965999722480774,"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/T10583","display_name":"Cancer-related Molecular Pathways","score":0.9965999722480774,"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/T10294","display_name":"Cell death mechanisms and regulation","score":0.0008999999845400453,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10937","display_name":"Telomeres, Telomerase, and Senescence","score":0.0008999999845400453,"subfield":{"id":"https://openalex.org/subfields/2737","display_name":"Physiology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/mdm2-inhibitors","display_name":"MDM2 inhibitors","score":0.9629999995231628},{"id":"https://openalex.org/keywords/nutlin-3","display_name":"Nutlin-3","score":0.9710000157356262},{"id":"https://openalex.org/keywords/p53","display_name":"p53","score":0.8069999814033508},{"id":"https://openalex.org/keywords/hmgb1","display_name":"HMGB1","score":0.8640000224113464},{"id":"https://openalex.org/keywords/hmgb1-secretion","display_name":"HMGB1 secretion","score":0.8519999980926514},{"id":"https://openalex.org/keywords/hmgb1-acetylation","display_name":"HMGB1 acetylation","score":0.9089999794960022},{"id":"https://openalex.org/keywords/apoptosis","display_name":"apoptosis","score":0.8240000009536743},{"id":"https://openalex.org/keywords/senescence-associated-secretory-phenotype","display_name":"senescence-associated secretory phenotype","score":0.8080000281333923},{"id":"https://openalex.org/keywords/premature-senescence","display_name":"premature senescence","score":0.8159999847412109},{"id":"https://openalex.org/keywords/normal-tissue-toxicity","display_name":"normal tissue toxicity","score":0.8199999928474426},{"id":"https://openalex.org/keywords/p21-expression","display_name":"p21 expression","score":0.6079999804496765},{"id":"https://openalex.org/keywords/reactive-oxygen-species","display_name":"reactive oxygen species","score":0.7139999866485596},{"id":"https://openalex.org/keywords/manganese-superoxide-dismutase","display_name":"manganese superoxide dismutase","score":0.6990000009536743},{"id":"https://openalex.org/keywords/mcf-7-cells","display_name":"MCF-7 cells","score":0.625}],"concepts":[{"id":"https://openalex.org/C190283241","wikidata":"https://www.wikidata.org/wiki/Q14599311","display_name":"Apoptosis","level":2,"score":0.653984546661377},{"id":"https://openalex.org/C96232424","wikidata":"https://www.wikidata.org/wiki/Q4118072","display_name":"Cancer cell","level":3,"score":0.5753387212753296},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.5689816474914551},{"id":"https://openalex.org/C522857546","wikidata":"https://www.wikidata.org/wiki/Q2070979","display_name":"Senescence","level":2,"score":0.5557314157485962},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.5435209274291992},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.5145410895347595},{"id":"https://openalex.org/C2776192174","wikidata":"https://www.wikidata.org/wiki/Q18028978","display_name":"Mdm2","level":3,"score":0.4834795594215393},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.44920504093170166},{"id":"https://openalex.org/C31573885","wikidata":"https://www.wikidata.org/wiki/Q304484","display_name":"Programmed cell death","level":3,"score":0.42638036608695984},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.14003300666809082},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.09810620546340942}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1158/1538-7445.am2011-4507","doi":"https://doi.org/10.1158/1538-7445.am2011-4507","is_oa":false,"landing_page_url":"https://doi.org/10.1158/1538-7445.am2011-4507","pdf_url":null,"source":{"id":"https://openalex.org/S168522863","display_name":"Cancer Research","issn_l":"0008-5472","issn":["0008-5472","1538-7445"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","doyens","jufo-3","ki-jl-3","medline","norway-2"],"host_organization":"https://openalex.org/P4310320273","host_organization_name":"American Association for Cancer Research","host_organization_lineage":["https://openalex.org/P4310320273"],"host_organization_lineage_names":["American Association for Cancer Research"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Cancer Research","raw_type":"journal-article"}],"best_oa_location":null,"sustainable_development_goals":[{"display_name":"Good health and well-being","score":0.979200005531311,"id":"https://metadata.un.org/sdg/3"}],"sustainable_development_goals_aurora":[{"display_name":"Good health and well-being","score":0.8100000023841858,"id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W2791511901","https://openalex.org/W2059729414","https://openalex.org/W2935649237","https://openalex.org/W2082627181","https://openalex.org/W2339852853","https://openalex.org/W2162414118","https://openalex.org/W2394369094","https://openalex.org/W3151504969","https://openalex.org/W2037680056","https://openalex.org/W2384087372"],"abstract_inverted_index":{"Abstract":[0],"An":[1],"attractive":[2],"therapeutic":[3],"approach":[4],"against":[5,145],"cancers":[6],"with":[7,123,172,194,235,363],"wild-type":[8],"(wt)":[9],"p53":[10,78,159,367],"is":[11,66,262],"the":[12,21,48,52,59,74,99,220,271,342,415,420],"emergent":[13],"class":[14],"of":[15,51,62,76,101,125,228,241,270,283,291,299,310,334,344,374,387,414,419],"small":[16],"molecule":[17],"MDM2":[18,64,87],"inhibitors,":[19],"including":[20,293],"imidazoline":[22],"nutlin-3":[23],"and":[24,38,86,149,161,175,199,206,222,256,265,319],"more":[25],"potent":[26],"spiro-oxindole":[27],"MI-63":[28,102,134,151,216,276,297,372],"(Ascenta":[29],"Therapeutics).":[30],"Both":[31],"can":[32,80,89],"rapidly":[33],"increase":[34,155,177],"intracellular":[35],"p53wt":[36,116,126,146,335,375],"levels":[37,160],"induce":[39,90],"apoptosis":[40,179],"or":[41,287,303,347],"a":[42,153,173,200,268,307,321,359],"senescence":[43,93,354],"growth":[44,197,356],"arrest,":[45],"depending":[46],"on":[47,138],"neoplastic":[49],"status":[50],"target":[53],"cell.":[54],"A":[55,211],"critical":[56],"question":[57],"in":[58,94,104,115,156,178,324,336,341,376],"clinical":[60],"development":[61],"such":[63],"inhibitors":[65],"their":[67],"potential":[68],"for":[69,249,423],"normal":[70,83,127,223],"tissue":[71,84],"toxicity.":[72],"In":[73,370],"absence":[75,343],"MDM2,":[77],"activation":[79],"cause":[81],"fatal":[82],"pathology;":[85],"inhibition":[88],"p53-dependent":[91],"cell":[92,317,349,382],"mouse":[95],"fibroblasts.":[96],"To":[97],"assess":[98],"effects":[100,103],"human":[105,118,128,140],"cells,":[106],"we":[107],"compared":[108],"treatment":[109,298],"(2.5-10":[110],"uM,":[111],"1-7":[112],"d)":[113],"responses":[114],"malignant":[117,221,377],"mammary":[119],"epithelial":[120,378],"cells":[121,142,148,170,192,224,379,393],"(MCF7)":[122],"those":[124],"foreskin":[129],"fibroblasts":[130,278,338],"(HCA2).":[131],"As":[132],"expected,":[133],"had":[135],"little":[136],"effect":[137],"p53mut":[139],"cancer":[141,147,392],"(MDA-231).":[143],"However,":[144],"fibroblasts,":[150],"produced":[152,320],"dose-dependent":[154],"both":[157,219],"nuclear":[158,226],"reporter":[162],"gene":[163],"(p21)":[164],"expression":[165],"within":[166,208],"24":[167,302],"h.":[168],"MCF7":[169],"responded":[171,193],"dose-":[174],"time-dependent":[176],"after":[180,306],"2":[181],"d":[182],"exposure":[183],"(vital":[184],"dye":[185],"uptake,":[186],"cleaved":[187],"PARP).":[188],"By":[189],"contrast,":[190,371],"HCA2":[191,300],"partially":[195],"reversible":[196],"arrest":[198,357],"senescent-like":[201],"phenotype":[202,274],"(increased":[203],"ROS,":[204],"SOD2,":[205],"SA-\u03b2gal)":[207],"3":[209],"days.":[210],"common":[212],"early":[213,385],"(24":[214],"h)":[215],"response":[217,399],"by":[218,254,339],"was":[225,252],"loss":[227],"high-mobility":[229],"group":[230],"box-1":[231],"protein":[232],"(HMGB1)":[233],"associated":[234,326],"its":[236,250],"active":[237],"extracellular":[238],"secretion.":[239,295,328],"Acetylation":[240],"this":[242],"damage-reporting":[243],"cytokine,":[244],"thought":[245],"to":[246,280],"be":[247,267],"required":[248],"secretion,":[251],"detected":[253],"western":[255],"mass":[257],"spectrometry":[258],"analyses.":[259],"Although":[260],"HMGB1":[261,388],"generally":[263],"pro-inflammatory":[264],"may":[266,394],"harbinger":[269],"senescence-associated":[272],"secretory":[273],"(SASP),":[275],"treated":[277],"failed":[279],"exhibit":[281],"induction":[282],"DNA":[284,345],"damage":[285,346],"foci":[286],"other":[288,348],"features":[289],"characteristic":[290],"SASP":[292,325,360],"IL-6":[294,327],"Surprisingly,":[296],"beginning":[301],"48":[304],"h":[305],"senescence-inducing":[308],"dose":[309],"ionizing":[311],"radiation":[312],"(10":[313],"Gy)":[314],"prevented":[315],"enlarged":[316],"morphology":[318],">80%":[322],"reduction":[323],"These":[329],"findings":[330],"indicate":[331],"that":[332,366],"upregulation":[333,373],"proliferating":[337],"MI-63,":[340],"stresses,":[350],"induces":[351],"an":[352],"incomplete":[353],"like":[355],"without":[358],"response,":[361],"consistent":[362],"our":[364],"finding":[365],"restrains":[368],"SASP.":[369],"caused":[380],"apoptotic":[381],"death.":[383],"The":[384],"release":[386],"from":[389],"these":[390],"dying":[391],"modulate":[395],"host":[396],"innate":[397],"immune":[398],"and/or":[400],"recruit":[401],"tumor":[402],"infiltrating":[403],"inflammatory":[404],"cells.":[405],"Citation":[406],"Format:":[407],"{Authors}.":[408],"{Abstract":[409],"title}":[410],"[abstract].":[411],"In:":[412],"Proceedings":[413],"102nd":[416],"Annual":[417],"Meeting":[418],"American":[421],"Association":[422],"Cancer":[424,434],"Research;":[425],"2011":[426],"Apr":[427],"2-6;":[428],"Orlando,":[429],"FL.":[430],"Philadelphia":[431],"(PA):":[432],"AACR;":[433],"Res":[435],"2011;71(8":[436],"Suppl):Abstract":[437],"nr":[438],"4507.":[439],"doi:10.1158/1538-7445.AM2011-4507":[440]},"counts_by_year":[],"updated_date":"2026-09-22T06:50:58.402377","created_date":"2025-10-10T00:00:00"}
