{"id":"https://openalex.org/W2466893496","doi":"https://doi.org/10.1002/hep.27208","title":"Reply","display_name":"Reply","publication_year":2014,"publication_date":"2014-05-05","ids":{"openalex":"https://openalex.org/W2466893496","doi":"https://doi.org/10.1002/hep.27208","mag":"2466893496","pmid":"https://pubmed.ncbi.nlm.nih.gov/24799327","pmcid":"https://www.ncbi.nlm.nih.gov/pmc/articles/4221577"},"language":"en","primary_location":{"id":"doi:10.1002/hep.27208","doi":"https://doi.org/10.1002/hep.27208","is_oa":false,"landing_page_url":"https://doi.org/10.1002/hep.27208","pdf_url":null,"source":{"id":"https://openalex.org/S156174673","display_name":"Hepatology","issn_l":"0270-9139","issn":["0270-9139","1527-3350"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310315671","host_organization_name":"Lippincott Williams & Wilkins","host_organization_lineage":["https://openalex.org/P4310315671","https://openalex.org/P4310318547"],"host_organization_lineage_names":["Lippincott Williams & Wilkins","Wolters Kluwer"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Hepatology","raw_type":"journal-article"},"volume":null,"type":"letter","is_traditional":true,"indexed_in":["crossref","pubmed"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4221577","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5068858118","display_name":"Bryan C. Fuchs","orcid":"https://orcid.org/0000-0002-2149-3081","observed_orcids":["https://orcid.org/0000-0002-2149-3081"]},"institutions":[{"id":"https://openalex.org/I136199984","display_name":"Harvard University","ror":"https://ror.org/03vek6s52","country_code":"US","type":"education","lineage":["https://openalex.org/I136199984"]},{"id":"https://openalex.org/I4210087915","display_name":"Massachusetts General Hospital","ror":"https://ror.org/002pd6e78","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4210087915","https://openalex.org/I48633490"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Bryan C. Fuchs","raw_affiliation_strings":["Division of Surgical Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Surgical Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA","institution_ids":["https://openalex.org/I136199984","https://openalex.org/I4210087915"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5007607351","display_name":"Yujin Hoshida","orcid":"https://orcid.org/0000-0001-9430-1426","observed_orcids":["https://orcid.org/0000-0001-9430-1426"]},"institutions":[{"id":"https://openalex.org/I4390039328","display_name":"Tisch Cancer Institute","ror":"https://ror.org/0317dzj93","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1320796813","https://openalex.org/I4390039328","https://openalex.org/I98704320"]},{"id":"https://openalex.org/I98704320","display_name":"Icahn School of Medicine at Mount Sinai","ror":"https://ror.org/04a9tmd77","country_code":"US","type":"education","lineage":["https://openalex.org/I1320796813","https://openalex.org/I98704320"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Yujin Hoshida","raw_affiliation_strings":["Liver Cancer Program, Tisch Cancer Institute, Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Liver Cancer Program, Tisch Cancer Institute, Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY","institution_ids":["https://openalex.org/I4390039328","https://openalex.org/I98704320"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5043519976","display_name":"Kenneth K. Tanabe","orcid":"https://orcid.org/0000-0003-1920-3417","observed_orcids":["https://orcid.org/0000-0003-1920-3417"]},"institutions":[{"id":"https://openalex.org/I136199984","display_name":"Harvard University","ror":"https://ror.org/03vek6s52","country_code":"US","type":"education","lineage":["https://openalex.org/I136199984"]},{"id":"https://openalex.org/I4210087915","display_name":"Massachusetts General Hospital","ror":"https://ror.org/002pd6e78","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4210087915","https://openalex.org/I48633490"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Kenneth K. Tanabe","raw_affiliation_strings":["Division of Surgical Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Surgical Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA","institution_ids":["https://openalex.org/I136199984","https://openalex.org/I4210087915"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":4,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":{"value":2900,"currency":"USD","value_usd":2900},"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":"61","issue":"2","first_page":"729","last_page":"730"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10073","display_name":"Hepatocellular Carcinoma Treatment and Prognosis","score":0.8695999979972839,"subfield":{"id":"https://openalex.org/subfields/2721","display_name":"Hepatology"},"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/T10073","display_name":"Hepatocellular Carcinoma Treatment and Prognosis","score":0.8695999979972839,"subfield":{"id":"https://openalex.org/subfields/2721","display_name":"Hepatology"},"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/T10966","display_name":"Liver physiology and pathology","score":0.10220000147819519,"subfield":{"id":"https://openalex.org/subfields/2721","display_name":"Hepatology"},"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/T11067","display_name":"Colorectal Cancer Treatments and Studies","score":0.010900000110268593,"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"}}],"keywords":[{"id":"https://openalex.org/keywords/erlotinib","display_name":"erlotinib","score":0.9120000004768372},{"id":"https://openalex.org/keywords/hepatocellular-carcinoma","display_name":"hepatocellular carcinoma","score":0.9959999918937683},{"id":"https://openalex.org/keywords/chemoprevention","display_name":"chemoprevention","score":0.8709999918937683},{"id":"https://openalex.org/keywords/liver-cirrhosis","display_name":"liver cirrhosis","score":0.8830000162124634},{"id":"https://openalex.org/keywords/egfr-inhibition","display_name":"EGFR inhibition","score":0.703000009059906},{"id":"https://openalex.org/keywords/egfr-mutation","display_name":"EGFR mutation","score":0.5870000123977661},{"id":"https://openalex.org/keywords/hepatic-stellate-cells","display_name":"hepatic stellate cells","score":0.9210000038146973},{"id":"https://openalex.org/keywords/liver-fibrosis","display_name":"liver fibrosis","score":0.9350000023841858},{"id":"https://openalex.org/keywords/chemoresistance","display_name":"chemoresistance","score":0.6650000214576721},{"id":"https://openalex.org/keywords/interstitial-lung-disease","display_name":"interstitial lung disease","score":0.753000020980835},{"id":"https://openalex.org/keywords/hepatotoxicity","display_name":"hepatotoxicity","score":0.5440000295639038},{"id":"https://openalex.org/keywords/minimum-effective-dose","display_name":"minimum effective dose","score":0.5609999895095825},{"id":"https://openalex.org/keywords/ki-67","display_name":"Ki-67","score":0.4560000002384186},{"id":"https://openalex.org/keywords/erk1-2-phosphorylation","display_name":"ERK1/2 phosphorylation","score":0.5239999890327454}],"concepts":[{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.44033506512641907}],"mesh":[{"descriptor_ui":"D000818","descriptor_name":"Animals","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006528","descriptor_name":"Carcinoma, Hepatocellular","qualifier_ui":"Q000517","qualifier_name":"prevention & control","is_major_topic":true},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008103","descriptor_name":"Liver Cirrhosis","qualifier_ui":"Q000517","qualifier_name":"prevention & control","is_major_topic":true},{"descriptor_ui":"D008113","descriptor_name":"Liver Neoplasms","qualifier_ui":"Q000517","qualifier_name":"prevention & control","is_major_topic":true},{"descriptor_ui":"D008297","descriptor_name":"Male","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D011799","descriptor_name":"Quinazolines","qualifier_ui":"Q000627","qualifier_name":"therapeutic use","is_major_topic":true},{"descriptor_ui":"D018450","descriptor_name":"Disease Progression","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D066246","descriptor_name":"ErbB Receptors","qualifier_ui":"Q000037","qualifier_name":"antagonists & inhibitors","is_major_topic":true}],"locations_count":3,"locations":[{"id":"doi:10.1002/hep.27208","doi":"https://doi.org/10.1002/hep.27208","is_oa":false,"landing_page_url":"https://doi.org/10.1002/hep.27208","pdf_url":null,"source":{"id":"https://openalex.org/S156174673","display_name":"Hepatology","issn_l":"0270-9139","issn":["0270-9139","1527-3350"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310315671","host_organization_name":"Lippincott Williams & Wilkins","host_organization_lineage":["https://openalex.org/P4310315671","https://openalex.org/P4310318547"],"host_organization_lineage_names":["Lippincott Williams & Wilkins","Wolters Kluwer"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Hepatology","raw_type":"journal-article"},{"id":"pmid:24799327","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/24799327","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":"Hepatology (Baltimore, Md.)","raw_type":"Letter"},{"id":"pmh:oai:pubmedcentral.nih.gov:4221577","doi":null,"is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4221577","pdf_url":null,"source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"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":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"Hepatology","raw_type":"Text"}],"best_oa_location":{"id":"pmh:oai:pubmedcentral.nih.gov:4221577","doi":null,"is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4221577","pdf_url":null,"source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"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":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"Hepatology","raw_type":"Text"},"sustainable_development_goals":[{"display_name":"Good health and well-being","score":0.9940000176429749,"id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[{"id":"https://openalex.org/G2448124205","display_name":"Molecular Prognostic Indicators in Liver Cirrhosis and Cancer","funder_award_id":"R01DK099558","funder_id":"https://openalex.org/F4320337357","funder_display_name":"National Institute of Diabetes and Digestive and Kidney Diseases"},{"id":"https://openalex.org/G8297309125","display_name":"Targeting diffuse liver metastases with Herpes virus","funder_award_id":"R01CA076183","funder_id":"https://openalex.org/F4320337351","funder_display_name":"National Cancer Institute"},{"id":"https://openalex.org/G8911033299","display_name":"The Role of EGF in Human Hepatocellular Transformation","funder_award_id":"K01CA140861","funder_id":"https://openalex.org/F4320337351","funder_display_name":"National Cancer Institute"}],"funders":[{"id":"https://openalex.org/F4320332161","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88"},{"id":"https://openalex.org/F4320337351","display_name":"National Cancer Institute","ror":"https://ror.org/040gcmg81"},{"id":"https://openalex.org/F4320337357","display_name":"National Institute of Diabetes and Digestive and Kidney Diseases","ror":"https://ror.org/00adh9b73"}],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":8,"referenced_works":["https://openalex.org/W1975915668","https://openalex.org/W2008463741","https://openalex.org/W2069076782","https://openalex.org/W2071058106","https://openalex.org/W2086702949","https://openalex.org/W2096096763","https://openalex.org/W2106036268","https://openalex.org/W2115497785"],"related_works":["https://openalex.org/W1975605376","https://openalex.org/W2069076782","https://openalex.org/W2017188321","https://openalex.org/W4362541053","https://openalex.org/W2132395321","https://openalex.org/W4391326421","https://openalex.org/W2106036268","https://openalex.org/W1527131381","https://openalex.org/W2073195217","https://openalex.org/W2465841147"],"abstract_inverted_index":{"We":[0,185,437],"appreciate":[1],"the":[2,100,173,183,217,258,360,371,381,405,411],"interest":[3],"of":[4,42,61,161,176,202,228,270,311,318,331,364,407,413,470,491,495,499],"Dong":[5,152,301],"et":[6,153,302],"al.":[7,154],"in":[8,65,178,225,238,272,333,349,367,380,410,419,432,449],"our":[9,66,179],"recent":[10],"article.1":[11],"As":[12,297],"they":[13],"point":[14],"out,":[15],"hepatocellular":[16],"carcinoma":[17],"(HCC)":[18],"cell":[19,230,276],"lines":[20,277],"are":[21,32,233,251,292],"largely":[22],"resistant":[23],"to":[24,163,197,205,215,257,322,358,403,426],"erlotinib":[25,46,62,95,130,177,206,268,289,304,332,366,387,442],"at":[26,374,400,423,452,501],"clinically":[27],"relevant":[28],"doses.":[29],"These":[30],"results":[31,127],"consistent":[33],"with":[34,45,110,194,308,421],"HCC":[35,124,162,195,203,271,275],"clinical":[36,285,356,384],"trials":[37,385],"where":[38,104],"only":[39],"a":[40,213,226,355,389,397],"minority":[41],"patients":[43,369,451],"treated":[44],"exhibited":[47],"disease":[48],"control.2,":[49],"3":[50],"Our":[51,126],"data":[52],"support":[53],"these":[54],"findings,":[55],"as":[56,69,388,396],"we":[57,261,352],"observed":[58,224],"no":[59],"effect":[60,98,175],"on":[63,99,147,168,182,212,267],"tumors":[64],"diethylnitrosamine":[67],"model":[68],"measured":[70],"by":[71,300],"several":[72],"endpoints":[73],"including":[74],"phospho-epidermal":[75],"growth":[76],"factor":[77],"receptor":[78],"(EGFR)":[79],"levels,":[80,85],"phospho-extracellular":[81],"signal-regulated":[82],"kinase":[83],"(ERK)":[84],"Ki67":[86],"staining,":[87],"tumor":[88],"histology,":[89],"and":[90,122,138,149,248,315,417,429,478],"gene-expression":[91],"signature":[92],"analysis.":[93],"Instead,":[94],"had":[96],"an":[97,280,445],"surrounding":[101],"cirrhotic":[102,148,219],"tissue,":[103],"suppressed":[105],"phospho-EGFR":[106],"levels":[107],"were":[108],"associated":[109,193,307],"reduced":[111],"hepatocyte":[112],"proliferation,":[113],"fewer":[114],"activated":[115],"hepatic":[116],"stellate":[117,249],"cells,":[118],"diminished":[119],"fibrosis":[120],"progression,":[121],"decreased":[123],"development.":[125],"suggest":[128],"that":[129,172,189,244,278,287,441],"does":[131],"not":[132,263],"have":[133,186,207,262,325,353,392],"appreciable":[134],"direct":[135,255],"antitumor":[136],"effects":[137,146,330],"instead":[139],"holds":[140],"potential":[141,159],"for":[142,337,346,455],"chemoprevention":[143,447],"through":[144],"its":[145],"fibrotic":[150],"liver.":[151,220],"also":[155,418],"raise":[156],"concern":[157],"over":[158],"resistance":[160,196,204],"EGFR":[164,222,281,376],"inhibition,":[165],"presumably":[166],"based":[167],"their":[169],"misfounded":[170],"notion":[171],"primary":[174],"models":[180],"is":[181,192,306,378],"HCC.":[184,456],"previously":[187],"shown":[188],"epithelial-to-mesenchymal":[190],"transition":[191],"erlotinib.4":[198],"However,":[199],"various":[200],"mechanisms":[201],"little":[208],"if":[209],"any":[210,265],"impact":[211],"strategy":[214,391,448],"modulate":[216],"underlying":[218],"The":[221,283,328],"mutations":[223,235,243],"subset":[227],"non-small":[229],"lung":[231,313],"cancers":[232],"somatic":[234],"(and":[236],"rare":[237],"HCC5).":[239],"More":[240],"important,":[241],"germline":[242],"could":[245],"affect":[246],"hepatocytes":[247],"cells":[250],"extraordinarily":[252],"rare.6":[253],"In":[254],"response":[256],"referenced":[259],"questions,":[260],"generated":[264],"datasets":[266,286],"treatment":[269,305],"animals":[273],"or":[274],"harbor":[279],"mutation.":[282],"largest":[284],"inform":[288],"toxicity":[290,324],"profiles":[291],"from":[293],"cancer":[294,409],"therapy":[295],"trials.":[296],"pointed":[298],"out":[299],"al.,":[303],"increased":[309],"risk":[310,454],"interstitial":[312],"disease7":[314],"case":[316],"reports":[317],"fatal":[319],"complications":[320],"due":[321],"liver":[323],"been":[326,393],"described.8":[327],"side":[329],"doses":[334,402,425],"typically":[335],"used":[336],"oncology":[338],"indications":[339],"(150":[340],"mg/day)":[341],"renders":[342],"this":[343],"dose":[344,363,373],"unsuitable":[345],"long":[347],"term-use":[348],"chemoprevention.":[350],"Accordingly,":[351],"launched":[354],"trial":[357],"determine":[359],"minimum":[361,372],"effective":[362,446],"daily":[365],"cirrhosis":[368,450],"(i.e.,":[370],"which":[375],"phosporylation":[377],"inhibited":[379],"liver).":[382],"Other":[383],"examining":[386],"prevention":[390],"initiated":[394],"both":[395],"single":[398],"agent":[399],"chemotherapeutic":[401],"reduce":[404],"incidence":[406],"oral":[408,414],"setting":[412],"leukoplakia":[415],"(NCT00402779)":[416],"combination":[420],"sulindac":[422],"lower":[424],"regress":[427],"duodenal":[428],"colorectal":[430],"adenomas":[431],"familial":[433],"adenomatous":[434],"polyposis":[435],"(NCT01187901).":[436],"remain":[438],"cautiously":[439],"optimistic":[440],"may":[443],"be":[444],"high":[453],"Bryan":[457],"C.":[458],"Fuchs,":[459],"Ph.D.1":[460],"Yujin":[461],"Hoshida,":[462],"M.D.,":[463],"Ph.D.2":[464],"Kenneth":[465],"K.":[466],"Tanabe,":[467],"M.D.1":[468],"1Division":[469],"Surgical":[471],"Oncology":[472],"Massachusetts":[473],"General":[474],"Hospital":[475],"Cancer":[476,485,488],"Center":[477],"Harvard":[479],"Medical":[480],"School":[481,498],"Boston,":[482],"MA":[483],"2Liver":[484],"Program":[486],"Tisch":[487],"Institute":[489],"Division":[490],"Liver":[492],"Diseases":[493],"Department":[494],"Medicine":[496,500],"Icahn":[497],"Mount":[502],"Sinai":[503],"New":[504],"York,":[505],"NY":[506]},"counts_by_year":[],"updated_date":"2026-10-31T12:09:11.096373","created_date":"2016-07-22T00:00:00"}
