{"id":"https://openalex.org/W1632005397","doi":null,"title":"Inherent resistance of human squamous carcinoma cell lines to methotrexate as a result of decreased polyglutamylation of this drug.","display_name":"Inherent resistance of human squamous carcinoma cell lines to methotrexate as a result of decreased polyglutamylation of this drug.","publication_year":1989,"publication_date":"1989-10-01","ids":{"openalex":"https://openalex.org/W1632005397","mag":"1632005397","pmid":"https://pubmed.ncbi.nlm.nih.gov/2475246"},"language":"en","primary_location":{"id":"pmid:2475246","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/2475246","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":"Cancer research","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/A5016722881","display_name":"Giuseppe Pizzorno","orcid":"https://orcid.org/0000-0001-7087-2806","observed_orcids":["https://orcid.org/0000-0001-7087-2806"]},"institutions":[{"id":"https://openalex.org/I32971472","display_name":"Yale University","ror":"https://ror.org/03v76x132","country_code":"US","type":"education","lineage":["https://openalex.org/I32971472"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"G Pizzorno","raw_affiliation_strings":["Department of Pharmacology and Medicine, Yale University School of Medicine, New Haven, Connecticut 06510"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Pharmacology and Medicine, Yale University School of Medicine, New Haven, Connecticut 06510","institution_ids":["https://openalex.org/I32971472"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5082146540","display_name":"Yu Chang","orcid":"https://orcid.org/0000-0003-1490-1961","observed_orcids":["https://orcid.org/0000-0003-1490-1961"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Y M Chang","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5091214681","display_name":"John J. McGuire","orcid":"https://orcid.org/0000-0003-0302-3884","observed_orcids":["https://orcid.org/0000-0003-0302-3884"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"J J McGuire","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"last","author":{"id":"https://openalex.org/A5104110678","display_name":"Joseph R. Bertino","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"J R Bertino","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":2.5871,"has_fulltext":false,"cited_by_count":62,"citation_normalized_percentile":{"value":0.90728608,"is_in_top_1_percent":false,"is_in_top_10_percent":true},"cited_by_percentile_year":{"min":89,"max":96},"biblio":{"volume":"49","issue":"19","first_page":"5275","last_page":"80"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10570","display_name":"Drug Transport and Resistance Mechanisms","score":0.9945999979972839,"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/T10570","display_name":"Drug Transport and Resistance Mechanisms","score":0.9945999979972839,"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/T11845","display_name":"Cancer therapeutics and mechanisms","score":0.0013000000035390258,"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/T10499","display_name":"Folate and B Vitamins Research","score":0.0008999999845400453,"subfield":{"id":"https://openalex.org/subfields/2745","display_name":"Rheumatology"},"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/methotrexate","display_name":"methotrexate","score":0.8799999952316284},{"id":"https://openalex.org/keywords/trimetrexate","display_name":"trimetrexate","score":0.9359999895095825},{"id":"https://openalex.org/keywords/drug-resistance","display_name":"drug resistance","score":0.6669999957084656},{"id":"https://openalex.org/keywords/squamous-cell-carcinoma","display_name":"squamous cell carcinoma","score":0.9139999747276306},{"id":"https://openalex.org/keywords/antifolate-drugs","display_name":"antifolate","score":0.7689999938011169},{"id":"https://openalex.org/keywords/folylpolyglutamate-synthetase","display_name":"folylpolyglutamate synthetase","score":0.9819999933242798},{"id":"https://openalex.org/keywords/dihydrofolate-reductase","display_name":"dihydrofolate reductase","score":0.9869999885559082},{"id":"https://openalex.org/keywords/fadu-cell-line","display_name":"FaDu cell line","score":0.6800000071525574}],"concepts":[{"id":"https://openalex.org/C2781059491","wikidata":"https://www.wikidata.org/wiki/Q422232","display_name":"Methotrexate","level":2,"score":0.8568974733352661},{"id":"https://openalex.org/C2781382166","wikidata":"https://www.wikidata.org/wiki/Q50573407","display_name":"Antifolate","level":4,"score":0.7676677703857422},{"id":"https://openalex.org/C2781320022","wikidata":"https://www.wikidata.org/wiki/Q417149","display_name":"Dihydrofolate reductase","level":3,"score":0.6652920842170715},{"id":"https://openalex.org/C81885089","wikidata":"https://www.wikidata.org/wiki/Q189082","display_name":"Cell culture","level":2,"score":0.6642228364944458},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.462327241897583},{"id":"https://openalex.org/C109316439","wikidata":"https://www.wikidata.org/wiki/Q246181","display_name":"Cytotoxicity","level":3,"score":0.413549542427063},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.34529197216033936},{"id":"https://openalex.org/C2778397455","wikidata":"https://www.wikidata.org/wiki/Q50429865","display_name":"Antimetabolite","level":3,"score":0.2921868860721588},{"id":"https://openalex.org/C202751555","wikidata":"https://www.wikidata.org/wiki/Q221681","display_name":"In vitro","level":2,"score":0.27151817083358765},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.24824896454811096},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.18840372562408447},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.08792802691459656}],"mesh":[{"descriptor_ui":"D000970","descriptor_name":"Antineoplastic Agents","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D000970","descriptor_name":"Antineoplastic Agents","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D002294","descriptor_name":"Carcinoma, Squamous Cell","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":false},{"descriptor_ui":"D002294","descriptor_name":"Carcinoma, Squamous Cell","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D004351","descriptor_name":"Drug Resistance","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006258","descriptor_name":"Head and Neck Neoplasms","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":false},{"descriptor_ui":"D006258","descriptor_name":"Head and Neck Neoplasms","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008727","descriptor_name":"Methotrexate","qualifier_ui":"Q000031","qualifier_name":"analogs & derivatives","is_major_topic":false},{"descriptor_ui":"D008727","descriptor_name":"Methotrexate","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D008727","descriptor_name":"Methotrexate","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D010453","descriptor_name":"Peptide Synthases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D010455","descriptor_name":"Peptides","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D011099","descriptor_name":"Polyglutamic Acid","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D011799","descriptor_name":"Quinazolines","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D011799","descriptor_name":"Quinazolines","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D013940","descriptor_name":"Thymidylate Synthase","qualifier_ui":"Q000378","qualifier_name":"metabolism","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":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D014407","descriptor_name":"Tumor Cells, Cultured","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D016597","descriptor_name":"Trimetrexate","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":2,"locations":[{"id":"pmid:2475246","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/2475246","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":"Cancer research","raw_type":"Journal Article"},{"id":"mag:1632005397","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/2475246","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":[{"display_name":"Good health and well-being","score":0.9476000070571899,"id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W2117852255","https://openalex.org/W1966633783","https://openalex.org/W6982574066","https://openalex.org/W2124713626","https://openalex.org/W1560690111","https://openalex.org/W2159800348","https://openalex.org/W1600598432","https://openalex.org/W2005493883","https://openalex.org/W2026126218","https://openalex.org/W1832330239"],"abstract_inverted_index":{"Three":[0],"human":[1,247],"squamous":[2,248],"carcinoma":[3],"cell":[4,31,57,99,125,142,154,175,180,199,212,236,249],"lines":[5,32,58,100],"(FaDu,":[6],"A253,":[7],"and":[8,17,34,50,80,114,210],"SQCC/Y1)":[9,35],"were":[10,59],"tested":[11],"for":[12,87],"sensitivity":[13,184],"to":[14,39,62,91,131,158,167,185,189,207,224,260],"methotrexate":[15,79,92,137,232,244],"(MTX)":[16],"trimetrexate,":[18,63],"a":[19,73,145],"second":[20],"generation":[21],"folate":[22],"antagonist":[23],"in":[24,183,229,245,257],"clinical":[25],"trials.":[26],"Two":[27],"of":[28,96,104,109,116,134,136,164,194,231,243,265],"the":[29,88,97,123,132,140,152,173,178,208,226,235,253],"three":[30,56,98,124,141],"(A253":[33],"showed":[36],"inherent":[37,258],"resistance":[38,90,128,259],"methotrexate,":[40,113,186],"when":[41],"cytotoxicity":[42],"was":[43,101,129,156,187],"evaluated":[44],"after":[45],"short":[46],"term":[47],"exposure":[48],"(4":[49],"24":[51],"h).":[52],"In":[53],"contrast,":[54],"all":[55],"markedly":[60],"sensitive":[61],"an":[64],"antifolate":[65],"which":[66,81],"is":[67,78,82,216,222],"taken":[68],"up":[69],"by":[70,72,94,112,139,172],"cells":[71,163,170,193],"different":[74],"transport":[75],"system":[76],"than":[77],"not":[83,119,217],"polyglutamylated.":[84],"The":[85,197],"basis":[86],"natural":[89],"shown":[93],"two":[95],"examined.":[102],"Levels":[103],"dihydrofolate":[105],"reductase":[106],"activity,":[107],"inhibition":[108],"this":[110,220,266],"enzyme":[111],"influx":[115],"MTX":[117,195],"did":[118],"differ":[120],"significantly":[121],"between":[122,234],"lines;":[126],"however,":[127],"correlated":[130],"amounts":[133],"polyglutamates":[135,230],"synthesized":[138,171],"lines.":[143,213,237],"After":[144],"24-h":[146],"incubation":[147],"with":[148],"10":[149],"microM":[150],"MTX,":[151],"A253":[153,198],"line":[155,200],"able":[157,188],"form":[159,190],"only":[160],"35.0":[161],"pmol/10(7)":[162,169,192],"polyglutamates,":[165],"compared":[166,206],"250":[168],"FaDu":[174,209],"line,":[176,181],"while":[177],"SQCC/Y1":[179,211],"intermediate":[182],"145":[191],"polyglutamates.":[196],"contained":[201],"less":[202],"folylpolyglutamate":[203],"synthetase":[204],"activity":[205],"However,":[214],"it":[215],"clear":[218],"if":[219],"difference":[221],"sufficient":[223],"explain":[225],"marked":[227],"differences":[228],"found":[233],"We":[238],"conclude":[239],"that":[240],"decreased":[241],"polyglutamylation":[242],"some":[246],"carcinomas":[250],"may":[251],"be":[252],"major":[254],"contributing":[255],"factor":[256],"high":[261],"dose":[262],"pulse":[263],"administration":[264],"drug.":[267]},"counts_by_year":[{"year":2022,"cited_by_count":1},{"year":2019,"cited_by_count":2},{"year":2017,"cited_by_count":1},{"year":2016,"cited_by_count":2},{"year":2012,"cited_by_count":2}],"updated_date":"2026-10-31T12:09:11.096373","created_date":"2016-06-24T00:00:00"}