{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T12:49:40Z","timestamp":1791982180350,"version":"4.4.0"},"reference-count":54,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T00:00:00Z","timestamp":1777075200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T00:00:00Z","timestamp":1777075200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL168060"],"award-info":[{"award-number":["HL168060"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI167971"],"award-info":[{"award-number":["AI167971"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DE034474"],"award-info":[{"award-number":["DE034474"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Head &amp; Neck"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Tobacco use is associated with worse outcomes in head and neck squamous cell carcinoma (HNSCC). Bitter taste receptor (T2R) activation induces apoptosis via calcium\u2010dependent signaling, and higher T2R expression correlates with increased survival in HNSCC. However, the effects of cigarette smoke on T2R signaling remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>HNSCC cell lines were treated with cigarette smoke condensate (CSC). T2R expression was measured by qPCR, and function evaluated by calcium imaging, viability, and apoptosis assays following stimulation with denatonium benzoate and flufenamic acid. T2R expression was also assessed in patient\u2010derived tumor tissue and The Cancer Genome Atlas (TCGA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>CSC reduced T2R expression, impaired calcium signaling, and diminished T2R\u2010mediated apoptosis, particularly in SCC47 cells. Lower expression was observed in CSC\u2010exposed patient\u2010derived tumor tissue and TCGA tumors from smokers versus nonsmokers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Cigarette smoke disrupts T2R signaling and reduces apoptosis in HNSCC, suggesting a mechanism by which ongoing tobacco use may alter tumor biology and treatment response.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hed.70290","type":"journal-article","created":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T07:34:45Z","timestamp":1777102485000},"page":"2745-2755","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cigarette Smoke Exposure Attenuates\n                    <scp>T2R<\/scp>\n                    \u2010Mediated Apoptosis in Head and Neck Squamous Cell Carcinoma"],"prefix":"10.1002","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-7775-111X","authenticated-orcid":false,"given":"Kyle","family":"Polen","sequence":"first","affiliation":[{"name":"Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Sywanycz","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head &amp; Neck Surgery University of Pennsylvania Health System  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavin","family":"Turner","sequence":"additional","affiliation":[{"name":"Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brianna L.","family":"Hill","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head &amp; Neck Surgery University of Pennsylvania Health System  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3713-3443","authenticated-orcid":false,"given":"Lily","family":"Huang","sequence":"additional","affiliation":[{"name":"Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoey A.","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head &amp; Neck Surgery University of Pennsylvania Health System  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Casey","family":"Hanna","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head &amp; Neck Surgery University of Pennsylvania Health System  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lovely","family":"Raghav","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head &amp; Neck Surgery University of Pennsylvania Health System  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devraj","family":"Basu","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head &amp; Neck Surgery University of Pennsylvania Health System  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head &amp; Neck Surgery University of Pennsylvania Health System  Philadelphia Pennsylvania USA"},{"name":"Department of Physiology Perelman School of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0186-2265","authenticated-orcid":false,"given":"Ryan M.","family":"Carey","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head &amp; Neck Surgery University of Pennsylvania Health System  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,25]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10555\u2010017\u20109689\u20106"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265\u2010023\u201001835\u20102"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572\u2010020\u201000224\u20103"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/medsci11020042"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/lary.25767"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.21037\/tlcr.2019.04.01"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoto.2022.0810"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.4103\/jcrt.JCRT_641_16"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2009.10.050"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.23944"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.24082"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1159\/000509427"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2021.113554"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109\u2010024\u201002490\u20100"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.202200775"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1168\u201007.2007"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0959\u20104388(00)00118\u20105"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0959\u20104388(96)80057\u20102"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/bies.950151003"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R100054200"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/1878\u20100261.13131"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2021.102499"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010022\u201012788\u2010z"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2022.121363"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.113437"},{"key":"e_1_2_10_27_1","unstructured":"R.Carey \u201cA Phase I Randomized Controlled Trial of Intratumoral Lidocaine Injection Before Transoral Robotic Surgery (TORS) and Neck Dissection for HPV\u2010Associated Oropharyngeal Squamous Cell Carcinoma Clinicaltrials.Gov \u201d2025 accessed February 8 2025 https:\/\/clinicaltrials.gov\/study\/NCT06747390."},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2014.02.140"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.28120"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.22.01966"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.23.00418"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00092.2017"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2006.03.008"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2019.183057"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1097\/CMR.0000000000000644"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535\u20107163.MCT\u201025\u20100358"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14129"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24086907"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010\u2010019\u201003679\u20105"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.52.2.356"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.01225"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u20102121\u201014\u201032"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571\u2010019\u20100227\u2010z"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.13\u2010242594"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/cbdd.13089"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.771949"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010024\u201007253\u2010y"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI72094"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1101\/2024.10.24.620094"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.21873\/anticanres.14069"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm7218a1"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.18332\/tpc\/163243"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0166565"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21103495"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200802\u2010334OC"}],"container-title":["Head &amp; Neck"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hed.70290","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/hed.70290","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hed.70290","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T12:21:22Z","timestamp":1791980482000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/hed.70290"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,25]]},"references-count":54,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1002\/hed.70290"],"URL":"https:\/\/doi.org\/10.1002\/hed.70290","archive":["Portico"],"relation":{},"ISSN":["1043-3074","1097-0347"],"issn-type":[{"value":"1043-3074","type":"print"},{"value":"1097-0347","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,25]]},"assertion":[{"value":"2025-07-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}