{"id":"https://openalex.org/W2013709489","doi":"https://doi.org/10.1158/1538-7445.am10-1390","title":"Abstract 1390: shRNA mediated suppression of thymidylate synthase results in an increased sensitivity to ionizing radiation similar to 5-fluoro-2\u2032-deoxyuridine","display_name":"Abstract 1390: shRNA mediated suppression of thymidylate synthase results in an increased sensitivity to ionizing radiation similar to 5-fluoro-2\u2032-deoxyuridine","publication_year":2010,"publication_date":"2010-04-01","ids":{"openalex":"https://openalex.org/W2013709489","doi":"https://doi.org/10.1158/1538-7445.am10-1390","mag":"2013709489"},"language":"en","primary_location":{"id":"doi:10.1158/1538-7445.am10-1390","doi":"https://doi.org/10.1158/1538-7445.am10-1390","is_oa":false,"landing_page_url":"http://doi.org/10.1158/1538-7445.am10-1390","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/A5023626926","display_name":"Sheryl A. Flanagan","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I27837315","display_name":"University of Michigan","ror":"https://ror.org/00jmfr291","country_code":"US","type":"education","lineage":["https://openalex.org/I27837315"]},{"id":"https://openalex.org/I4210114445","display_name":"Michigan Medicine","ror":"https://ror.org/01zcpa714","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4210114445"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Sheryl A. Flanagan","raw_affiliation_strings":["1Univ. of Michigan Medical School, Ann Arbor, MI"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Univ. of Michigan Medical School, Ann Arbor, MI","institution_ids":["https://openalex.org/I27837315","https://openalex.org/I4210114445"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5067190256","display_name":"Mikhail A. Nikiforov","orcid":"https://orcid.org/0000-0001-7868-0518","observed_orcids":["https://orcid.org/0000-0001-7868-0518"]},"institutions":[{"id":"https://openalex.org/I1292894508","display_name":"Roswell Park Comprehensive Cancer Center","ror":"https://ror.org/0499dwk57","country_code":"US","type":"facility","lineage":["https://openalex.org/I1292894508"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Mikhail A. Nikiforov","raw_affiliation_strings":["2Roswell Park Cancer Institute, Buffalo, NY"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"2Roswell Park Cancer Institute, Buffalo, NY","institution_ids":["https://openalex.org/I1292894508"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5028074528","display_name":"Sudha Mannava","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1292894508","display_name":"Roswell Park Comprehensive Cancer Center","ror":"https://ror.org/0499dwk57","country_code":"US","type":"facility","lineage":["https://openalex.org/I1292894508"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Sudha Mannava","raw_affiliation_strings":["2Roswell Park Cancer Institute, Buffalo, NY"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"2Roswell Park Cancer Institute, Buffalo, NY","institution_ids":["https://openalex.org/I1292894508"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5108367844","display_name":"Donna S. Shewach","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I27837315","display_name":"University of Michigan","ror":"https://ror.org/00jmfr291","country_code":"US","type":"education","lineage":["https://openalex.org/I27837315"]},{"id":"https://openalex.org/I4210114445","display_name":"Michigan Medicine","ror":"https://ror.org/01zcpa714","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4210114445"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Donna S. Shewach","raw_affiliation_strings":["1Univ. of Michigan Medical School, Ann Arbor, MI"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Univ. of Michigan Medical School, Ann Arbor, MI","institution_ids":["https://openalex.org/I27837315","https://openalex.org/I4210114445"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":3,"corresponding_author_ids":[],"corresponding_institution_ids":[],"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":"70","issue":"8_Supplement","first_page":"1390","last_page":"1390"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11176","display_name":"Radiation Therapy and Dosimetry","score":0.5268999934196472,"subfield":{"id":"https://openalex.org/subfields/2740","display_name":"Pulmonary and Respiratory Medicine"},"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/T11176","display_name":"Radiation Therapy and Dosimetry","score":0.5268999934196472,"subfield":{"id":"https://openalex.org/subfields/2740","display_name":"Pulmonary and Respiratory Medicine"},"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/T10123","display_name":"DNA Repair Mechanisms","score":0.21359999477863312,"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/T11359","display_name":"Effects of Radiation Exposure","score":0.042399998754262924,"subfield":{"id":"https://openalex.org/subfields/2741","display_name":"Radiology, Nuclear Medicine and Imaging"},"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/thymidylate-synthase","display_name":"thymidylate synthase","score":0.9850000143051147},{"id":"https://openalex.org/keywords/radiosensitization","display_name":"radiosensitization","score":0.8579999804496765},{"id":"https://openalex.org/keywords/ionizing-radiation","display_name":"ionizing radiation","score":0.8629999756813049},{"id":"https://openalex.org/keywords/5-fluorodeoxyuridine","display_name":"5-fluorodeoxyuridine","score":0.9810000061988831},{"id":"https://openalex.org/keywords/fluoropyrimidine","display_name":"fluoropyrimidine","score":0.9539999961853027},{"id":"https://openalex.org/keywords/shrna-knockdown","display_name":"shRNA knockdown","score":0.7699999809265137},{"id":"https://openalex.org/keywords/mismatch-repair-deficiency","display_name":"mismatch repair deficiency","score":0.7620000243186951},{"id":"https://openalex.org/keywords/nucleotide-misincorporation","display_name":"nucleotide misincorporation","score":0.8450000286102295},{"id":"https://openalex.org/keywords/dna-repair","display_name":"DNA repair","score":0.44999998807907104},{"id":"https://openalex.org/keywords/colorectal-cancer","display_name":"colorectal cancer","score":0.7580000162124634},{"id":"https://openalex.org/keywords/hct116-cells","display_name":"HCT116 cells","score":0.8519999980926514},{"id":"https://openalex.org/keywords/sw620-cells","display_name":"SW620 cells","score":0.7940000295639038}],"concepts":[{"id":"https://openalex.org/C123321153","wikidata":"https://www.wikidata.org/wiki/Q22676802","display_name":"Thymidylate synthase","level":4,"score":0.9386568069458008},{"id":"https://openalex.org/C2777111502","wikidata":"https://www.wikidata.org/wiki/Q419140","display_name":"Deoxyuridine","level":3,"score":0.534958004951477},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.5174144506454468},{"id":"https://openalex.org/C109316439","wikidata":"https://www.wikidata.org/wiki/Q246181","display_name":"Cytotoxicity","level":3,"score":0.5156441926956177},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.4976697266101837},{"id":"https://openalex.org/C512185932","wikidata":"https://www.wikidata.org/wiki/Q28745","display_name":"Nucleotide","level":3,"score":0.48458993434906006},{"id":"https://openalex.org/C134935766","wikidata":"https://www.wikidata.org/wiki/Q210538","display_name":"DNA repair","level":3,"score":0.4407663643360138},{"id":"https://openalex.org/C143425029","wikidata":"https://www.wikidata.org/wiki/Q5205747","display_name":"DNA damage","level":3,"score":0.4372768998146057},{"id":"https://openalex.org/C153911025","wikidata":"https://www.wikidata.org/wiki/Q7202","display_name":"Molecular biology","level":1,"score":0.3989903926849365},{"id":"https://openalex.org/C552990157","wikidata":"https://www.wikidata.org/wiki/Q7430","display_name":"DNA","level":2,"score":0.3600011169910431},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.3567241132259369},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.3272216022014618},{"id":"https://openalex.org/C202751555","wikidata":"https://www.wikidata.org/wiki/Q221681","display_name":"In vitro","level":2,"score":0.2527889609336853},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.23769450187683105},{"id":"https://openalex.org/C2780456651","wikidata":"https://www.wikidata.org/wiki/Q238512","display_name":"Fluorouracil","level":3,"score":0.15527385473251343},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.1261414885520935},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.06520023941993713}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1158/1538-7445.am10-1390","doi":"https://doi.org/10.1158/1538-7445.am10-1390","is_oa":false,"landing_page_url":"http://doi.org/10.1158/1538-7445.am10-1390","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":0.9391000270843506,"id":"https://metadata.un.org/sdg/3"}],"sustainable_development_goals_aurora":[{"display_name":"Good health and well-being","score":0.6499999761581421,"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/W2410195708","https://openalex.org/W1997445564","https://openalex.org/W2121802959","https://openalex.org/W1986189875","https://openalex.org/W2100680341","https://openalex.org/W2760815521","https://openalex.org/W2747101336","https://openalex.org/W2414052839","https://openalex.org/W1991644354","https://openalex.org/W2033918102"],"abstract_inverted_index":{"Abstract":[0],"The":[1,20],"fluoropyrimidines":[2],"(FPs),":[3],"5-fluorouracil":[4],"(5-FU)":[5],"and":[6,43,53,68,135,173,192,261,296,386,403],"5-fluoro-2\u2019-deoxyuridine":[7,29],"(FdUrd),":[8],"are":[9],"widely":[10],"used":[11,167],"as":[12,129,154,156,158],"radiosensitizers":[13],"in":[14,39,125,133,183,190,198,251,264,349,365,384,412],"the":[15,208,375,382,388,391,438,445,460,465],"treatment":[16,400],"of":[17,34,41,45,49,79,149,169,176,187,259,304,377,390,459,464],"gastrointestinal":[18],"cancer.":[19],"FPs":[21,157],"exert":[22],"their":[23],"cytotoxic":[24],"effects":[25],"through":[26],"activation":[27],"to":[28,82,115,145,200,207,277,367,408,426,449],"5\u2019-monophosphate":[30],"(FdUMP),":[31],"an":[32,196],"inhibitor":[33],"thymidylate":[35],"synthase":[36],"(TS),":[37],"resulting":[38],"depletion":[40,67,78,303],"dTTP":[42,66,80,305,323],"inhibition":[44],"DNA":[46,56,87,394,410],"synthesis.":[47],"Incorporation":[48],"fluorodeoxyuridine":[50],"5\u2019-triphosphate":[51],"(FdUTP)":[52],"dUTP":[54],"into":[55,86,393],"can":[57],"also":[58],"elicit":[59],"cytotoxicity.":[60,74,397],"Radiosensitization":[61],"by":[62,101,112,379,423],"FdUrd":[63,113,121,212,262,295,357,380,402],"correlates":[64],"with":[65,73,211,326,331,338,343,401],"S-phase":[69,268],"arrest,":[70],"but":[71,138,328,340,359],"not":[72,90,387,435],"We":[75,143],"hypothesized":[76],"that":[77,104,204,374],"leads":[81],"incorrect":[83],"nucleotide":[84,123],"incorporation":[85,389],"which,":[88],"if":[89],"repaired,":[91],"augments":[92],"cell":[93,266],"death":[94],"following":[95,257,270],"irradiation.":[96],"This":[97,432],"hypothesis":[98,373],"was":[99,205,255,273,434,447],"supported":[100],"our":[102,372],"findings":[103],"mismatch":[105],"repair":[106],"(MMR)-deficient":[107],"HCT116":[108,134,191],"were":[109],"better":[110],"radiosensitized":[111],"compared":[114,276],"MMR-proficient":[116],"HCT":[117],"116":[118],"cells.":[119],"Furthermore,":[120],"produced":[122,178,299,353,361],"misincorporations":[124],"DNA,":[126],"measured":[127],"directly":[128,422],"pSP189":[130,252],"plasmid":[131,253],"mutations":[132,254],"SW620":[136],"cells,":[137],"only":[139],"at":[140,437],"radiosensitizing":[141,160],"concentrations.":[142],"wished":[144],"determine":[146],"whether":[147],"suppression":[148,258,272,298,352],"TS":[150,165,184,188,271,297,332,344,351,418],"protein":[151],"would":[152],"be":[153,406,420],"effective":[155],"a":[159,179,248,300,362],"strategy.":[161],"To":[162],"selectively":[163],"inhibit":[164],"we":[166],"each":[168],"two":[170],"shRNAs,":[171],"TS1":[172],"TS2,":[174],"both":[175,265,360],"which":[177],"\u2265":[180],"90%":[181],"decrease":[182,383,427],"expression.":[185],"Suppression":[186],"expression":[189],"HT29":[193],"cells":[194],"elicited":[195],"increase":[197,209,250,364],"sensitivity":[199,366],"ionizing":[201],"radiation":[202],"(IR)":[203],"similar":[206,249,301,363],"observed":[210,256],"(IC50)":[213,263],"(Radiation":[214],"Enhancement":[215],"Ratio":[216],"(RER)":[217],"=":[218],"HCT116:":[219],"1.4":[220,234,238],"\u00b1":[221,225,230,235,239,244],"0.08":[222,231],"(TS1),":[223,237,281,289,308,316],"1.5":[224,229],"0.04":[226,240],"(TS2)":[227,241,283,291,310,318],"vs.":[228,242,284,292,311,319],"(FdUrd);":[232,286,313],"HT29:":[233,287,314],"0.06":[236],"1.6":[243],"0.3":[245],"(FdUrd)).":[246,294],"Additionally,":[247],"TS,":[260],"lines.":[267],"accumulation":[269],"slightly":[274,342],"attenuated":[275],"drug":[278,392],"(HCT116:":[279,306],"70%":[280,309],"60%":[282],"75%":[285,290,315],"55%":[288],"85%":[293],"initial":[302],"65%":[307],"40%":[312],"50%":[317,320],"(FdUrd)),":[321],"however":[322],"levels":[324,335],"rebounded":[325],"FdUrd,":[327,339],"remained":[329],"low":[330],"suppression.":[333,345],"dATP":[334],"increased":[336],"profoundly":[337],"decreased":[341],"Despite":[346],"these":[347],"differences":[348],"dNTPs,":[350],"less":[354],"cytotoxicity":[355],"than":[356,415],"(IC50),":[358],"IR.":[368],"These":[369],"results":[370],"support":[371],"mechanism":[376],"radiosensitzation":[378],"is":[381],"dTTP,":[385],"or":[395,417],"its":[396],"Therefore,":[398],"clinical":[399],"IR":[404],"could":[405,419],"titrated":[407],"maximize":[409],"mismatches":[411],"tumors":[413],"rather":[414],"cytotoxicity,":[416],"targeted":[421],"shRNA":[424],"methods":[425],"normal":[428],"tissue":[429],"toxicity.":[430],"Note:":[431],"abstract":[433],"presented":[436],"AACR":[439],"101st":[440,461],"Annual":[441,462],"Meeting":[442,463],"2010":[443,471],"because":[444],"presenter":[446],"unable":[448],"attend.":[450],"Citation":[451],"Format:":[452],"{Authors}.":[453],"{Abstract":[454],"title}":[455],"[abstract].":[456],"In:":[457],"Proceedings":[458],"American":[466],"Association":[467],"for":[468],"Cancer":[469,479],"Research;":[470],"Apr":[472],"17-21;":[473],"Washington,":[474],"DC.":[475],"Philadelphia":[476],"(PA):":[477],"AACR;":[478],"Res":[480],"2010;70(8":[481],"Suppl):Abstract":[482],"nr":[483],"1390.":[484]},"counts_by_year":[],"updated_date":"2026-07-14T23:27:15.235271","created_date":"2025-10-10T00:00:00"}
