{"id":"https://openalex.org/W190480427","doi":null,"title":"TARGETING THE MDM2-P53 AXIS FOR THE TREATMENT OF DEDIFFERENTIATED LIPOSARCOMA","display_name":"TARGETING THE MDM2-P53 AXIS FOR THE TREATMENT OF DEDIFFERENTIATED LIPOSARCOMA","publication_year":2014,"publication_date":"2014-01-01","ids":{"openalex":"https://openalex.org/W190480427","mag":"190480427"},"language":"en","primary_location":{"id":"pmh:oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-1537","doi":null,"is_oa":true,"landing_page_url":"https://digitalcommons.library.tmc.edu/utgsbs_dissertations/498","pdf_url":"https://digitalcommons.library.tmc.edu/cgi/viewcontent.cgi?article=1537&context=utgsbs_dissertations","source":{"id":"https://openalex.org/S4377196655","display_name":"Digital Commons-TMC (Texas Medical Center)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1337852284","host_organization_name":"Texas Medical Center","host_organization_lineage":["https://openalex.org/I1337852284"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Dissertations & Theses (Open Access)","raw_type":"text"},"volume":null,"type":"dissertation","is_traditional":true,"indexed_in":[],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://digitalcommons.library.tmc.edu/cgi/viewcontent.cgi?article=1537&context=utgsbs_dissertations","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5075984233","display_name":"Katelynn Bill","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":true,"raw_author_name":"Katelynn Bill","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"corresponding_author_ids":["https://openalex.org/A5075984233"],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10583","display_name":"Cancer-related Molecular Pathways","score":0.9404000043869019,"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":0.9404000043869019,"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/T10253","display_name":"Sarcoma Diagnosis and Treatment","score":0.05849999934434891,"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/T12820","display_name":"Chromatin Remodeling and Cancer","score":9.999999747378752e-05,"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"}}],"keywords":[{"id":"https://openalex.org/keywords/dedifferentiated-liposarcoma","display_name":"dedifferentiated liposarcoma","score":1.0},{"id":"https://openalex.org/keywords/mdm2","display_name":"MDM2","score":0.8090000152587891},{"id":"https://openalex.org/keywords/p53","display_name":"p53","score":0.9860000014305115},{"id":"https://openalex.org/keywords/mdm2-inhibitors","display_name":"MDM2 inhibitors","score":0.875},{"id":"https://openalex.org/keywords/mdm2-amplification","display_name":"MDM2 amplification","score":0.8740000128746033},{"id":"https://openalex.org/keywords/wild-type-p53","display_name":"wild-type p53","score":0.8790000081062317},{"id":"https://openalex.org/keywords/apoptosis","display_name":"apoptosis","score":0.5690000057220459},{"id":"https://openalex.org/keywords/cell-cycle-arrest","display_name":"cell cycle arrest","score":0.9829999804496765},{"id":"https://openalex.org/keywords/xenograft-models","display_name":"xenograft models","score":0.824999988079071},{"id":"https://openalex.org/keywords/nutlin-3a","display_name":"Nutlin-3a","score":0.8100000023841858},{"id":"https://openalex.org/keywords/gene-expression-profiling","display_name":"gene expression profiling","score":0.6769999861717224},{"id":"https://openalex.org/keywords/drug-target-identification","display_name":"drug target identification","score":0.4580000042915344}],"concepts":[{"id":"https://openalex.org/C2779568860","wikidata":"https://www.wikidata.org/wiki/Q1827425","display_name":"Liposarcoma","level":3,"score":0.641182541847229},{"id":"https://openalex.org/C2776192174","wikidata":"https://www.wikidata.org/wiki/Q18028978","display_name":"Mdm2","level":3,"score":0.5849913954734802},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.38178011775016785},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.3234368562698364},{"id":"https://openalex.org/C2778256501","wikidata":"https://www.wikidata.org/wiki/Q223911","display_name":"Sarcoma","level":2,"score":0.20555710792541504},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.16404810547828674},{"id":"https://openalex.org/C142724271","wikidata":"https://www.wikidata.org/wiki/Q7208","display_name":"Pathology","level":1,"score":0.13866835832595825},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.09426391124725342},{"id":"https://openalex.org/C81885089","wikidata":"https://www.wikidata.org/wiki/Q189082","display_name":"Cell culture","level":2,"score":0.0}],"mesh":[],"locations_count":2,"locations":[{"id":"pmh:oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-1537","doi":null,"is_oa":true,"landing_page_url":"https://digitalcommons.library.tmc.edu/utgsbs_dissertations/498","pdf_url":"https://digitalcommons.library.tmc.edu/cgi/viewcontent.cgi?article=1537&context=utgsbs_dissertations","source":{"id":"https://openalex.org/S4377196655","display_name":"Digital Commons-TMC (Texas Medical Center)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1337852284","host_organization_name":"Texas Medical Center","host_organization_lineage":["https://openalex.org/I1337852284"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Dissertations & Theses (Open Access)","raw_type":"text"},{"id":"mag:190480427","doi":null,"is_oa":false,"landing_page_url":"https://digitalcommons.library.tmc.edu/utgsbs_dissertations/498/","pdf_url":null,"source":null,"license":null,"license_id":null,"version":null,"is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":null}],"best_oa_location":{"id":"pmh:oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-1537","doi":null,"is_oa":true,"landing_page_url":"https://digitalcommons.library.tmc.edu/utgsbs_dissertations/498","pdf_url":"https://digitalcommons.library.tmc.edu/cgi/viewcontent.cgi?article=1537&context=utgsbs_dissertations","source":{"id":"https://openalex.org/S4377196655","display_name":"Digital Commons-TMC (Texas Medical Center)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1337852284","host_organization_name":"Texas Medical Center","host_organization_lineage":["https://openalex.org/I1337852284"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Dissertations & Theses (Open Access)","raw_type":"text"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","score":0.9763000011444092,"display_name":"Good health and well-being"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":true,"pdf":true},"content_urls":{"pdf":"https://content.openalex.org/works/W190480427.pdf","grobid_xml":"https://content.openalex.org/works/W190480427.grobid-xml"},"referenced_works_count":158,"referenced_works":["https://openalex.org/W81826961","https://openalex.org/W85477779","https://openalex.org/W1512214997","https://openalex.org/W1527655497","https://openalex.org/W1541315026","https://openalex.org/W1576330810","https://openalex.org/W1586740324","https://openalex.org/W1596376363","https://openalex.org/W1621305026","https://openalex.org/W1650797637","https://openalex.org/W1892579032","https://openalex.org/W1893251984","https://openalex.org/W1929606469","https://openalex.org/W1964963490","https://openalex.org/W1965239527","https://openalex.org/W1965531638","https://openalex.org/W1966203663","https://openalex.org/W1967778523","https://openalex.org/W1968820967","https://openalex.org/W1969044026","https://openalex.org/W1969255091","https://openalex.org/W1970286627","https://openalex.org/W1975697981","https://openalex.org/W1976261939","https://openalex.org/W1977393886","https://openalex.org/W1977497204","https://openalex.org/W1977767602","https://openalex.org/W1979250970","https://openalex.org/W1980858272","https://openalex.org/W1982933649","https://openalex.org/W1984092997","https://openalex.org/W1985139403","https://openalex.org/W1988013021","https://openalex.org/W1988968354","https://openalex.org/W1989589242","https://openalex.org/W1990054550","https://openalex.org/W1990532502","https://openalex.org/W1990882829","https://openalex.org/W1991494214","https://openalex.org/W1992947288","https://openalex.org/W1993263392","https://openalex.org/W1993864973","https://openalex.org/W1994482948","https://openalex.org/W1994487360","https://openalex.org/W1994852323","https://openalex.org/W1997594001","https://openalex.org/W1997637120","https://openalex.org/W1998287298","https://openalex.org/W2001274114","https://openalex.org/W2002705413","https://openalex.org/W2002936090","https://openalex.org/W2008887283","https://openalex.org/W2009845042","https://openalex.org/W2011912935","https://openalex.org/W2012053348","https://openalex.org/W2012183441","https://openalex.org/W2014583828","https://openalex.org/W2015208216","https://openalex.org/W2016107093","https://openalex.org/W2016334273","https://openalex.org/W2016492849","https://openalex.org/W2017379014","https://openalex.org/W2018153447","https://openalex.org/W2020097472","https://openalex.org/W2020474446","https://openalex.org/W2022416218","https://openalex.org/W2022529631","https://openalex.org/W2023061767","https://openalex.org/W2023612761","https://openalex.org/W2024996523","https://openalex.org/W2025722611","https://openalex.org/W2026121915","https://openalex.org/W2028737011","https://openalex.org/W2032474685","https://openalex.org/W2033791403","https://openalex.org/W2034335825","https://openalex.org/W2037039805","https://openalex.org/W2038491907","https://openalex.org/W2038930059","https://openalex.org/W2041051519","https://openalex.org/W2045086385","https://openalex.org/W2045740354","https://openalex.org/W2046314426","https://openalex.org/W2048105812","https://openalex.org/W2056530510","https://openalex.org/W2058402966","https://openalex.org/W2061050157","https://openalex.org/W2062612693","https://openalex.org/W2062718503","https://openalex.org/W2065955521","https://openalex.org/W2067240980","https://openalex.org/W2067787818","https://openalex.org/W2068577449","https://openalex.org/W2069111865","https://openalex.org/W2070990294","https://openalex.org/W2071028149","https://openalex.org/W2071079337","https://openalex.org/W2073533521","https://openalex.org/W2074114480","https://openalex.org/W2074545297","https://openalex.org/W2076147908","https://openalex.org/W2077423253","https://openalex.org/W2077858999","https://openalex.org/W2080533553","https://openalex.org/W2084525187","https://openalex.org/W2085096689","https://openalex.org/W2086177683","https://openalex.org/W2086797990","https://openalex.org/W2091151265","https://openalex.org/W2097933346","https://openalex.org/W2099077093","https://openalex.org/W2099459640","https://openalex.org/W2099907467","https://openalex.org/W2100494757","https://openalex.org/W2104225295","https://openalex.org/W2105882193","https://openalex.org/W2109560931","https://openalex.org/W2110523744","https://openalex.org/W2112996193","https://openalex.org/W2113370608","https://openalex.org/W2114103020","https://openalex.org/W2115772647","https://openalex.org/W2117932700","https://openalex.org/W2118103951","https://openalex.org/W2118471037","https://openalex.org/W2119637533","https://openalex.org/W2120420804","https://openalex.org/W2121550925","https://openalex.org/W2123242499","https://openalex.org/W2125972676","https://openalex.org/W2126650918","https://openalex.org/W2128560398","https://openalex.org/W2132027179","https://openalex.org/W2132888849","https://openalex.org/W2134410951","https://openalex.org/W2136344041","https://openalex.org/W2137893910","https://openalex.org/W2140533811","https://openalex.org/W2145252755","https://openalex.org/W2149669709","https://openalex.org/W2150027419","https://openalex.org/W2154343665","https://openalex.org/W2155786178","https://openalex.org/W2155906069","https://openalex.org/W2158005145","https://openalex.org/W2160178368","https://openalex.org/W2160752563","https://openalex.org/W2161378536","https://openalex.org/W2164998999","https://openalex.org/W2167424472","https://openalex.org/W2170494099","https://openalex.org/W2171620774","https://openalex.org/W2210130869","https://openalex.org/W2319494954","https://openalex.org/W2328261580","https://openalex.org/W2793249378","https://openalex.org/W3212033154","https://openalex.org/W4247069559"],"related_works":["https://openalex.org/W2217748520","https://openalex.org/W4308875172","https://openalex.org/W4416266995","https://openalex.org/W4389513543","https://openalex.org/W2951587879","https://openalex.org/W4281705492","https://openalex.org/W4282963912","https://openalex.org/W2023143184","https://openalex.org/W4389279791","https://openalex.org/W4361301747"],"abstract_inverted_index":{"Dedifferentiated":[0],"liposarcoma":[1,154],"(DDLPS)":[2],"is":[3,57,72],"an":[4],"aggressive":[5],"malignancy":[6],"characterized":[7,60],"by":[8],"a":[9,58,101,109,121,239,285,351,362],"high":[10],"rate":[11],"of":[12,42,52,68,76,92,99,106,124,145,150,245,255,277,295,297,326,336,346,368],"recurrence":[13],"and":[14,62,95,132,148,199,232,236,262,310,318,330,356],"dismal":[15],"patient":[16,21],"outcome.":[17],"Minimal":[18],"improvement":[19],"in":[20,26,176,181,209,215,238,272,280,284,300,361,371],"survival":[22],"has":[23],"been":[24],"made":[25],"the":[27,32,43,50,63,74,97,143,216,256,293,327,344,372],"last":[28],"several":[29],"decades,":[30],"highlighting":[31],"crucial":[33],"need":[34],"for":[35],"improved":[36,53],"therapeutic":[37,54,112,337],"strategies.":[38],"A":[39],"better":[40],"understanding":[41,325],"molecular":[44],"deregulations":[45],"underlying":[46],"DDLPS":[47,125,177,205,301],"would":[48],"facilitate":[49,115],"discovery":[51],"approaches.":[55],"MDM2":[56,70,146,162,198,259,298],"well":[59,225],"oncoprotein":[61],"most":[64],"known":[65,82],"negative":[66],"regulator":[67],"p53.":[69,86,187],"amplification":[71,147],"considered":[73],"\u201challmark\u201d":[75],"DDLPS.":[77],"Additionally,":[78],"these":[79,116,266],"tumors":[80],"are":[81],"to":[83,89,201,221,253,291,348],"harbor":[84],"wild-type":[85],"We":[87,314],"sought":[88],"take":[90],"advantage":[91],"this":[93,341,369],"knowledge":[94],"evaluate":[96],"role":[98],"SAR405838,":[100],"novel":[102],"small":[103],"molecule":[104],"inhibitor":[105],"MDM2,":[107,355],"as":[108,166,224,226,334],"potential":[110],"anti-DDLPS":[111,243,282,359],"strategy.":[113],"To":[114],"studies,":[117],"we":[118],"first":[119],"developed":[120],"large":[122],"set":[123],"experimental":[126],"tools,":[127],"specifically":[128],"human":[129],"cell":[130,137,155,229,267],"lines":[131,138,156],"xenograft":[133],"mouse":[134],"models.":[135],"These":[136],"were":[139,164,247,270,312],"further":[140,192,322,366],"characterized,":[141],"confirming":[142],"presence":[144],"lack":[149],"p53":[151,158,202],"mutations.":[152],"Other":[153],"harboring":[157],"mutations,":[159],"but":[160,179],"no":[161],"amplification,":[163],"used":[165],"controls.":[167],"Initial":[168],"experiments":[169,269,306],"demonstrated":[170,193],"that":[171,184,194,320],"SAR405838":[172,195,207,246,278,347],"was":[173],"highly":[174],"active":[175],"cells":[178,183,309],"not":[180],"LPS":[182],"exhibit":[185],"mutated":[186],"Cell":[188],"culture":[189],"based":[190,268],"assays":[191],"selectively":[196,349],"targeted":[197],"led":[200],"activation.":[203],"In":[204],"cells,":[206,302],"resulted":[208,279],"exemplary":[210],"anti-proliferation,":[211],"with":[212],"EC50":[213],"values":[214],"low":[217],"nanomolar":[218],"range":[219],"(0.13":[220],"0.49":[222],"nM),":[223],"successfully":[227],"induced":[228],"cycle":[230],"(G1":[231],"G2":[233],"phase)":[234],"arrest":[235],"apoptosis":[237],"dose-dependent":[240,286],"manner.":[241],"The":[242],"effects":[244,283,360],"significantly":[248],"more":[249],"pronounced":[250],"when":[251],"compared":[252],"those":[254],"older":[257],"generation":[258],"inhibitors":[260],"Nutlin-3a":[261],"MI-219.":[263],"Most":[264],"importantly,":[265],"replicated":[271],"vivo":[273],"where":[274],"oral":[275],"administration":[276],"potent":[281],"manner":[287],"(50-200":[288],"mg/kg).":[289],"Finally,":[290],"determine":[292],"mechanism":[294],"action":[296],"inhibition":[299],"gene":[303],"expression":[304],"array":[305],"on":[307],"SAR405838-treated":[308],"xenografts":[311],"conducted.":[313],"identified":[315],"multiple":[316],"pathways":[317],"genes":[319],"can":[321,331],"enhance":[323],"our":[324],"MDM2-p53":[328],"pathway":[329],"be":[332],"studied":[333],"biomarkers":[335],"response.":[338],"Taken":[339],"together,":[340],"study":[342],"highlights":[343],"ability":[345],"inhibit":[350],"biologically":[352],"relevant":[353],"target,":[354],"induce":[357],"potent,":[358],"pre-clinical":[363],"investigation":[364],"supporting":[365],"evaluation":[367],"compound":[370],"clinical":[373],"context.":[374]},"counts_by_year":[],"updated_date":"2026-11-07T11:25:07.637180","created_date":"2016-06-24T00:00:00"}
