{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T15:48:18Z","timestamp":1791388098202,"version":"4.3.3"},"reference-count":49,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,6,11]],"date-time":"2020-06-11T00:00:00Z","timestamp":1591833600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004756","name":"Emil Aaltosen S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004756","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004012","name":"Jane ja Aatos Erkon S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004012","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oral Diseases"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Oral squamous cell carcinoma (OSCC), the most common oral malignancy, shows an increasing rate of incidence worldwide. In spite of the recent advances in cancer research, OSCC therapy continues to have unfavourable outcomes, and thus, patient's prognosis remains relatively poor. Current research has been devoted to identifying novel therapeutic targets also in the tumour microenvironment (TME). Histamine and its G\u2010protein\u2010coupled receptors (H1R\u2010H4R) play vital roles in multiple cancer\u2010associated processes in TME, where histamine is mainly produced by mast cells. However, oral epithelial cells were recently shown to produce low concentrations of histamine in autocrine and paracrine modes. These findings, together with the discovery of the high\u2010affinity histamine H4 receptor, have led to a massive increase in our understanding of histamine functions. In this review, we aim to summarize the most recent findings regarding histamine and its receptors and their involvement in oral carcinogenesis\u2014from oral potentially malignant disorders (OPMDs) to invasive OSCC. Importantly, histamine receptors are differentially expressed in OPMDs and OSCC. Furthermore, H1R and H4R are associated with clinicopathological characteristics of OSCC patients, suggesting a role in prognosis. Due to the enormous success of histamine\u2010based medications, histamine receptors may also represent promising and viable drug targets in oral cancer.<\/jats:p>","DOI":"10.1111\/odi.13411","type":"journal-article","created":{"date-parts":[[2020,5,12]],"date-time":"2020-05-12T15:30:21Z","timestamp":1589297421000},"page":"1090-1096","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Nothing to sneeze at: Histamine and histamine receptors in oral carcinogenesis"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9455-3823","authenticated-orcid":false,"given":"Abdelhakim","family":"Salem","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Diseases Clinicum University of Helsinki Helsinki Finland"},{"name":"Translational Immunology Research Program (TRIMM) Research Program Unit (RPU) University of Helsinki Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuula","family":"Salo","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Diseases Clinicum University of Helsinki Helsinki Finland"},{"name":"Translational Immunology Research Program (TRIMM) Research Program Unit (RPU) University of Helsinki Helsinki Finland"},{"name":"Cancer and Translational Medicine Research Unit University of Oulu Oulu Finland"},{"name":"Oulu University Hospital Oulu Finland"},{"name":"Helsinki University Hospital (HUS) Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,6,11]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2005.12.044"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.25207"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.4103\/0973-029X.33959"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6602750"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21492"},{"issue":"4","key":"e_1_2_11_7_1","first-page":"4921","article-title":"Inhibition of histamine receptor H3R suppresses prostate cancer growth, invasion and increases apoptosis via the AR pathway","volume":"16","author":"Chen J.","year":"2018","journal-title":"Oncology Letters"},{"issue":"6","key":"e_1_2_11_8_1","first-page":"4443","article-title":"Histamine inhibits cell proliferation and modulates the expression of Bcl\u20102 family proteins via the H2 receptor in human pancreatic cancer cells","volume":"26","author":"Cricco G.","year":"2006","journal-title":"Anticancer Research"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/00008390-200306000-00003"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/9235080"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00784-012-0784-3"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01392"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2015.12.024"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2014.05.007"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0757.2011.00401.x"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00293.2007"},{"issue":"3","key":"e_1_2_11_17_1","first-page":"215","article-title":"Histamine and histamine receptor regulation of gastrointestinal cancers","volume":"1","author":"Kennedy L.","year":"2012","journal-title":"Translational Gastrointestinal Cancer"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40169-016-0108-3"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2018.00218"},{"key":"e_1_2_11_20_1","first-page":"201","volume-title":"Histamine H4 receptor: A novel drug target in immunoregulation and inflammation","author":"Konttinen Y. 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