{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T20:26:24Z","timestamp":1771273584292,"version":"3.50.1"},"reference-count":54,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2019,4,10]],"date-time":"2019-04-10T00:00:00Z","timestamp":1554854400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005634","name":"Suomen Hammasl\u00e4\u00e4k\u00e4riseura Apollonia","doi-asserted-by":"publisher","award":["Abdelhakim Salem"],"award-info":[{"award-number":["Abdelhakim Salem"]}],"id":[{"id":"10.13039\/501100005634","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007634","name":"Ida Montinin S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","award":["Abdelhakim Salem"],"award-info":[{"award-number":["Abdelhakim Salem"]}],"id":[{"id":"10.13039\/100007634","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009067","name":"K. Albin Johanssons Stiftelse","doi-asserted-by":"publisher","award":["Abdelhakim Salem"],"award-info":[{"award-number":["Abdelhakim Salem"]}],"id":[{"id":"10.13039\/501100009067","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007083","name":"Orionin Tutkimuss\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","award":["Abdelhakim Salem"],"award-info":[{"award-number":["Abdelhakim Salem"]}],"id":[{"id":"10.13039\/501100007083","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006383","name":"Sy\u00f6p\u00e4j\u00e4rjest\u00f6t","doi-asserted-by":"publisher","award":["Abdelhakim Salem"],"award-info":[{"award-number":["Abdelhakim Salem"]}],"id":[{"id":"10.13039\/501100006383","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Suomalais-Norjalainen L\u00e4\u00e4ketieteen S\u00e4\u00e4ti\u00f6","award":["Abdelhakim Salem"],"award-info":[{"award-number":["Abdelhakim Salem"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Human \u03b2-defensin 2 (hBD-2) is a potent antimicrobial peptide that participates in defense against invading bacteria. We recently showed that bacterial components and histamine, through histamine H4 receptor (H4R), are involved in the pathogenesis of the potentially malignant lesion, oral lichen planus (OLP). However, the underlying mechanisms remain unknown. We, therefore, investigated the role of hBD2\u2013histamine crosstalk signaling in promoting OLP pathology. Biopsies from OLP and oral tongue squamous cell carcinoma (OTSCC) patients, and healthy controls were used. Two OTSCC cell lines and normal human oral keratinocytes (HOKs) were used. HBD-2 and other targets were mapped by immunostaining and analyzed by ImageJ2 software. The highly sensitive droplet-digital PCR technology and qRT-PCR were utilized to study the clinically derived and in vitro samples, respectively. H4R was challenged with the specific agonist HST-10 and inverse agonist ST-1007. HBD-2 was highly induced in OLP lesions. In contrast, hBD2 expression was attenuated in OTSCC tissues, while very low levels of hBD-2 messenger RNA (mRNA) were observed in OTSCC cells. Together with tumor necrosis factor-\u03b1 (TNF-\u03b1), histamine upregulated hBD-2 mRNA expression in HOKs. Activation of H4R seems to modulate the expression of epithelial hBD-2. These findings suggest the involvement of hBD-2 in the pathogenesis of OLP and may, thus, be harnessed for therapeutic interventions in OLP.<\/jats:p>","DOI":"10.3390\/ijms20071780","type":"journal-article","created":{"date-parts":[[2019,4,10]],"date-time":"2019-04-10T11:25:08Z","timestamp":1554895508000},"page":"1780","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Human \u03b2-Defensin 2 Expression in Oral Epithelium: Potential Therapeutic Targets in Oral Lichen Planus"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9455-3823","authenticated-orcid":false,"given":"Abdelhakim","family":"Salem","sequence":"first","affiliation":[{"name":"Department of Clinical Medicine, Clinicum, University of Helsinki, 00014 Helsinki, Finland"},{"name":"Translational Immunology Research Program, University of Helsinki, 00014 Helsinki, Finland"},{"name":"Department of Oral and Maxillofacial Diseases, Clinicum, University of Helsinki, 00014 Helsinki, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rabeia","family":"Almahmoudi","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Diseases, Clinicum, University of Helsinki, 00014 Helsinki, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaana","family":"Hagstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Pathology, Helsinki University Hospital, Helsinki, Finland and Translational Cancer Medicine Research Program, Faculty of Medicine, University of Helsinki, 00014 Helsinki, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3336-1710","authenticated-orcid":false,"given":"Holger","family":"Stark","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical and Medicinal Chemistry, Heinrich Heine University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Nordstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Helsinki University and Helsinki Hospital, 00014 Helsinki, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6039-0088","authenticated-orcid":false,"given":"Tuula","family":"Salo","sequence":"additional","affiliation":[{"name":"Translational Immunology Research Program, University of Helsinki, 00014 Helsinki, Finland"},{"name":"Department of Oral and Maxillofacial Diseases, Clinicum, University of Helsinki, 00014 Helsinki, Finland"},{"name":"Medical Research Centre, Oulu University Hospital, 90220 Oulu, Finland"},{"name":"Cancer and Translational Medicine Research Unit, University of Oulu, FI-90014 Oulu, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kari K.","family":"Eklund","sequence":"additional","affiliation":[{"name":"Translational Immunology Research Program, University of Helsinki, 00014 Helsinki, Finland"},{"name":"Department of Internal Medicine, Helsinki University and Helsinki Hospital, 00014 Helsinki, Finland"},{"name":"Department of Rheumatology, Helsinki University and Helsinki University Hospital, and Orton Orthopedic Hospital and Research Institute, 00014 Helsinki, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,4,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1002\/biot.200700148","article-title":"Defensins: Antimicrobial peptides for therapeutic development","volume":"2","author":"Verma","year":"2007","journal-title":"Biotechnol. J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1038\/nri1180","article-title":"Defensins: Antimicrobial peptides of innate immunity","volume":"3","author":"Ganz","year":"2003","journal-title":"Nat. Rev. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"11333","DOI":"10.18632\/oncotarget.2416","article-title":"Overexpression of human \u03b2-defensin 2 promotes growth and invasion during esophageal carcinogenesis","volume":"5","author":"Shi","year":"2014","journal-title":"Oncotarget"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. Clin."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1111\/j.1601-0825.2000.tb00105.x","article-title":"The epidemiology of tongue cancer: A review of global incidence","volume":"6","author":"Moore","year":"2000","journal-title":"Oral Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1007\/s10555-007-9082-y","article-title":"Metastasis of squamous cell carcinoma of the oral tongue","volume":"26","author":"Sano","year":"2007","journal-title":"Cancer Metastasis Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1097\/01.cco.0000219250.15041.f8","article-title":"Disease mechanism and biomarkers of oral squamous cell carcinoma","volume":"18","author":"Brinkman","year":"2006","journal-title":"Curr. Opin. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.4161\/cc.8.13.8985","article-title":"Chronic inflammation; the tumor microenvironment and carcinogenesis","volume":"8","author":"Gonda","year":"2009","journal-title":"Cell Cycle"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Whitmore, S.E., and Lamont, R.J. (2014). Oral bacteria and cancer. PLoS Pathog., 10.","DOI":"10.1371\/journal.ppat.1003933"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"5715719","DOI":"10.1155\/2016\/5715719","article-title":"Immunosuppression Induced by Chronic Inflammation and the Progression to Oral Squamous Cell Carcinoma","volume":"2016","author":"Sun","year":"2016","journal-title":"Mediat. Inflamm."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1053\/j.seminoncol.2015.09.007","article-title":"The hallmarks of premalignant conditions: A molecular basis for cancer prevention","volume":"Volume 43","author":"Ryan","year":"2016","journal-title":"Seminars in Oncology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.ccr.2012.02.022","article-title":"Accessories to the crime: Functions of cells recruited to the tumor microenvironment","volume":"21","author":"Hanahan","year":"2012","journal-title":"Cancer Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"866","DOI":"10.12998\/wjcc.v2.i12.866","article-title":"Precancerous lesions of oral mucosa","volume":"2","author":"Yardimci","year":"2014","journal-title":"World J. Clin. Cases"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1111\/eos.12416","article-title":"Role of the high mobility group box 1 signalling axes via the receptor for advanced glycation end-products and toll-like receptor-4 in the immunopathology of oral lichen planus: A potential drug target?","volume":"126","author":"Salem","year":"2018","journal-title":"Eur. J. Oral Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1002\/ijc.31025","article-title":"Cancer risk of Lichen planus: A cohort study of 13,100 women in Finland","volume":"142","author":"Halonen","year":"2018","journal-title":"Int. J. Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1111\/bjd.14995","article-title":"Histamine metabolism and transport are deranged in human keratinocytes in oral lichen planus","volume":"176","author":"Salem","year":"2017","journal-title":"Br. J. Dermatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1111\/odi.12290","article-title":"Histamine H4 receptor in oral lichen planus","volume":"21","author":"Salem","year":"2015","journal-title":"Oral Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1007\/s13402-017-0336-6","article-title":"Histamine H4 receptor signalling in tongue cancer and its potential role in oral carcinogenesis-a short report","volume":"40","author":"Salem","year":"2017","journal-title":"Cell. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/S0304-3835(99)00171-8","article-title":"Pattern of expression of beta-defensins in oral squamous cell carcinoma","volume":"143","author":"Abiko","year":"1999","journal-title":"Cancer Lett."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/j.oraloncology.2008.11.012","article-title":"Psoriasin (S100A7) up-regulation in oral squamous cell carcinoma and its relation to clinicopathologic features","volume":"45","author":"Kesting","year":"2009","journal-title":"Oral Oncol."},{"key":"ref_21","first-page":"174","article-title":"Expression of human beta-defensins-1-4 in thyroid cancer cells and new insight on biologic activity of hBD-2 in vitro","volume":"36","author":"Zhuravel","year":"2014","journal-title":"Exp. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.1007\/s10495-014-1036-6","article-title":"Activation of histamine H4 receptor inhibits TNF\u03b1\/IMD-0354-induced apoptosis in human salivary NS-SV-AC cells","volume":"19","author":"Stegajev","year":"2014","journal-title":"Apoptosis"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"214","DOI":"10.2340\/00015555-2533","article-title":"Alterations in Factors Involved in Differentiation and Barrier Function in the Epithelium in Oral and Genital Lichen Planus","volume":"97","author":"Danielsson","year":"2017","journal-title":"Acta Derm. Venereol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5705","DOI":"10.1038\/onc.2016.84","article-title":"The role of barrier genes in epidermal malignancy","volume":"35","author":"Darido","year":"2016","journal-title":"Oncogene"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"29186","DOI":"10.1038\/srep29186","article-title":"The presence of bacteria within tissue provides insights into the pathogenesis of oral lichen planus","volume":"6","author":"Choi","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"386","DOI":"10.3389\/fimmu.2014.00386","article-title":"TLR-Dependent Human Mucosal Epithelial Cell Responses to Microbial Pathogens","volume":"5","author":"McClure","year":"2014","journal-title":"Front. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1097\/DAD.0000000000000807","article-title":"Altered Expression of Toll-like Receptors in Human Oral Epithelium in Oral Lichenoid Reactions","volume":"39","author":"Salem","year":"2017","journal-title":"Am. J. Dermatopathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2740","DOI":"10.1128\/IAI.67.6.2740-2745.1999","article-title":"Production of beta-defensin antimicrobial peptides by the oral mucosa and salivary glands","volume":"67","author":"Mathews","year":"1999","journal-title":"Infect. Immun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"7028","DOI":"10.1074\/jbc.M109.091090","article-title":"Specific binding and chemotactic activity of mBD4 and its functional orthologue hBD2 to CCR6-expressing cells","volume":"285","author":"Yang","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1189\/jlb.0111004","article-title":"Human \u03b2-defensin-2 enhances IFN-\u03b3 and IL-10 production and suppresses IL-17 production in T cells","volume":"89","author":"Kanda","year":"2011","journal-title":"J. Leukoc. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"230","DOI":"10.4172\/2155-9899.1000230","article-title":"An Inflammatory Cytokine Milieu is Prominent in Premalignant Oral Lesions; but Subsides when Lesions Progress to Squamous Cell Carcinoma","volume":"5","author":"Woodford","year":"2014","journal-title":"J. Clin. Cell. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1111\/j.1365-2133.2009.09090.x","article-title":"Human papillomavirus-associated induction of human beta-defensins in anal intraepithelial neoplasia","volume":"160","author":"Kreuter","year":"2009","journal-title":"Br. J. Dermatol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1038\/nature07205","article-title":"Cancer-related inflammation","volume":"454","author":"Mantovani","year":"2008","journal-title":"Nature"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1111\/j.1399-302X.2009.00512.x","article-title":"Loss of human beta-defensin 1; 2; and 3 expression in oral squamous cell carcinoma","volume":"24","author":"Joly","year":"2009","journal-title":"Oral Microbiol. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1007\/s004280000303","article-title":"Differential expression of human beta-defensin 2 in keratinized and non-keratinized oral epithelial lesions; immunohistochemistry and in situ hybridization","volume":"438","author":"Abiko","year":"2001","journal-title":"Virchows Arch."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"22943","DOI":"10.1038\/srep22943","article-title":"Preliminary analysis of salivary microbiome and their potential roles in oral lichen planus","volume":"6","author":"Wang","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1111\/j.1600-0765.2006.00879.x","article-title":"Expression of beta-defensin-2 in human gingival epithelial cells in response to challenge with Porphyromonas gingivalis in vitro","volume":"41","author":"Taguchi","year":"2006","journal-title":"J. Periodontal Res."},{"key":"ref_38","first-page":"127","article-title":"Periodontal pathogens promote epithelial-mesenchymal transition in oral squamous carcinoma cells in vitro","volume":"12","author":"Abdulkareem","year":"2018","journal-title":"Cell Adhes. Migr."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/s10555-011-9286-z","article-title":"The significant role of mast cells in cancer","volume":"30","author":"Khazaie","year":"2011","journal-title":"Cancer Metastasis Rev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2155","DOI":"10.1002\/hed.25207","article-title":"Extracellular interleukin-17F has a protective effect in oral tongue squamous cell carcinoma","volume":"40","author":"Almahmoudi","year":"2018","journal-title":"Head Neck"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1111\/j.1476-5381.2009.00151.x","article-title":"The role of histamine H4 receptor in immune and inflammatory disorders","volume":"157","author":"Zampeli","year":"2009","journal-title":"Br. J. Pharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1111\/j.1476-5381.2009.00250.x","article-title":"Molecular and biochemical pharmacology of the histamine H4 receptor","volume":"157","author":"Leurs","year":"2009","journal-title":"Br. J. Pharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"C1916","DOI":"10.1152\/ajpcell.00293.2007","article-title":"Histamine enhances the production of human beta-defensin-2 in human keratinocytes","volume":"293","author":"Kanda","year":"2007","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1002\/1521-4141(200104)31:4<1066::AID-IMMU1066>3.0.CO;2-#","article-title":"Evaluation of the effects of peptide antibiotics human beta-defensins-1\/-2 and LL-37 on histamine release and prostaglandin D2 production from mast cells","volume":"31","author":"Niyonsaba","year":"2001","journal-title":"Eur. J. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"345","DOI":"10.4049\/jimmunol.1300023","article-title":"\u03b2-Defensins activate human mast cells via Mas-related gene X2","volume":"191","author":"Subramanian","year":"2013","journal-title":"J. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.femsim.2005.01.008","article-title":"Transcriptional regulation of beta-defensin-2 by lipopolysaccharide in cultured human cervical carcinoma (HeLa) cells","volume":"45","author":"Mineshiba","year":"2005","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.bcp.2004.10.006","article-title":"Histamine H1 receptor antagonist blocks histamine-induced proinflammatory cytokine production through inhibition of Ca2+-dependent protein kinase C, Raf\/MEK\/ERK and IKK\/I kappa B\/NF-kappa B signal cascades","volume":"69","author":"Matsubara","year":"2005","journal-title":"Biochem. Pharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1016\/j.intimp.2006.06.005","article-title":"STAT1 phosphorylation and cleavage is regulated by the histamine (H4) receptor in human atopic and non-atopic lymphocytes","volume":"6","author":"Horr","year":"2006","journal-title":"Int. Immunopharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.1101\/gad.13.11.1382","article-title":"Inflammatory mast cells up-regulate angiogenesis during squamous epithelial carcinogenesis","volume":"13","author":"Coussens","year":"1999","journal-title":"Genes Dev."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Massari, N.A., Nicoud, M.B., and Medina, V.A. (2018). Histamine receptors and cancer pharmacology: An update. Br. J. Pharmacol.","DOI":"10.1111\/bph.14535"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1111\/bph.12137","article-title":"Therapeutic potential of histamine H4 receptor agonists in triple-negative human breast cancer experimental model","volume":"170","author":"Croci","year":"2013","journal-title":"Br. J. Pharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.ejphar.2010.12.033","article-title":"Receptor-specific functional efficacies of alkyl imidazoles as dual histamine H3\/H4 receptor ligands","volume":"654","author":"Kottke","year":"2011","journal-title":"Eur. J. Pharmacol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"7186","DOI":"10.1016\/j.bmc.2009.08.059","article-title":"2;4-Diaminopyrimidines as histamine H4 receptor ligands\u2014Scaffold optimization and pharmacological characterization","volume":"17","author":"Sander","year":"2009","journal-title":"Bioorg. Med. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Van Ginkel, J.H., Huibers, M.M.H., van Es, R.J.J., de Bree, R., and Willems, S.M. (2017). Droplet digital PCR for detection and quantification of circulating tumor DNA in plasma of head and neck cancer patients. BMC Cancer, 17.","DOI":"10.1186\/s12885-017-3424-0"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/7\/1780\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:44:28Z","timestamp":1760186668000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/7\/1780"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,10]]},"references-count":54,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2019,4]]}},"alternative-id":["ijms20071780"],"URL":"https:\/\/doi.org\/10.3390\/ijms20071780","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,10]]}}}