{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T09:18:22Z","timestamp":1790068702061,"version":"4.0.1"},"reference-count":36,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,2,4]],"date-time":"2024-02-04T00:00:00Z","timestamp":1707004800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Lasers Surg Med"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Systemically delivered hedgehog inhibitors including vismodegib and sonidegib are widely used to treat basal cell carcinomas (BCCs). Ablative fractional laser (AFL)\u2010assisted topical delivery of vismodegib has been demonstrated in preclinical studies. The aim of this explorative clinical study was to evaluate intratumoral vismodegib concentrations and effect on hedgehog pathway gene expression following AFL\u2010assisted topical vismodegib delivery to BCCs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In an open\u2010label clinical trial, 16 nodular BCCs (in <jats:italic>n<\/jats:italic>\u2009=\u20099 patients) received one application of CO<jats:sub>2<\/jats:sub>\u2010AFL (40\u2009mJ\/microbeam, 10% density) followed by topical vismodegib emulsion. After 3\u20134 days, vismodegib concentrations in tumor biopsies (<jats:italic>n<\/jats:italic>\u2009=\u200915) and plasma were analyzed and compared with samples from patients receiving oral treatment (<jats:italic>n<\/jats:italic>\u2009=\u20093). GLI1, GLI2, PTCH1, and PTCH2 expression was determined by quantitative polymerase chain reaction (<jats:italic>n<\/jats:italic>\u2009=\u20097) and GLI1 additionally by in situ hybridization (<jats:italic>n<\/jats:italic>\u2009=\u20093).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Following AFL\u2010assisted topical administration, vismodegib was detected in 14\/15 BCCs and reached a median concentration of 6.2\u2009\u00b5mol\/L, which compared to concentrations in BCC tissue from patients receiving oral vismodegib (9.5\u2009\u00b5mol\/L, <jats:italic>n<\/jats:italic>\u2009=\u20093, <jats:italic>p<\/jats:italic>\u2009=\u20090.8588). Topical vismodegib reduced intratumoral GLI1 expression by 51%, GLI2 by 55%, PTCH1 and PTCH2 each by 73% (<jats:italic>p<\/jats:italic>\u2009\u2264\u20090.0304) regardless of vismodegib concentrations (<jats:italic>p<\/jats:italic>\u2009\u2265\u20090.3164). In situ hybridization demonstrated that GLI1 expression was restricted to tumor tissue and downregulated in response to vismodegib exposure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>A single AFL\u2010assisted topical application of vismodegib resulted in clinically relevant intratumoral drug concentrations and significant reductions in hedgehog pathway gene expressions.<\/jats:p><\/jats:sec>","DOI":"10.1002\/lsm.23766","type":"journal-article","created":{"date-parts":[[2024,2,5]],"date-time":"2024-02-05T04:59:51Z","timestamp":1707109191000},"page":"239-248","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Laser\u2010assisted topical delivery of vismodegib reduces hedgehog gene expression in human basal cell carcinomas in vivo"],"prefix":"10.1002","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4578-684X","authenticated-orcid":false,"given":"Uffe H.","family":"Olesen","sequence":"first","affiliation":[{"name":"Department of Dermatology Copenhagen University Hospital\u2014Bispebjerg Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9994-7848","authenticated-orcid":false,"given":"Kristian K\u00e5ber","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Department of Dermatology Copenhagen University Hospital\u2014Bispebjerg Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4272-4889","authenticated-orcid":false,"given":"Katrine","family":"Togsverd\u2010Bo","sequence":"additional","affiliation":[{"name":"Department of Dermatology Copenhagen University Hospital\u2014Bispebjerg Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5510-2712","authenticated-orcid":false,"given":"Edyta","family":"Biskup","sequence":"additional","affiliation":[{"name":"Department of Pathology Copenhagen University Hospital\u2014Herlev Herlev Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anni Linnet","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Department of Oncology Copenhagen University Hospital\u2014Herlev Herlev Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4815-2153","authenticated-orcid":false,"given":"Malene","family":"Jackerott","sequence":"additional","affiliation":[{"name":"Leo Pharma A\/S Ballerup Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4358-5574","authenticated-orcid":false,"given":"Gael","family":"Clergeaud","sequence":"additional","affiliation":[{"name":"Department of Health Technology Technical University of Denmark Lyngby Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1048-127X","authenticated-orcid":false,"given":"Thomas L.","family":"Andresen","sequence":"additional","affiliation":[{"name":"Department of Health Technology Technical University of Denmark Lyngby Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1250-2035","authenticated-orcid":false,"given":"Merete","family":"Haedersdal","sequence":"additional","affiliation":[{"name":"Department of Dermatology Copenhagen University Hospital\u2014Bispebjerg Copenhagen Denmark"},{"name":"Department of Clinical Medicine Copenhagen University Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,2,4]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/CAD.0000000000000551"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-0568"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2503"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-10-2736"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(15)70100-2"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1113713"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.16230"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-017-3286-5"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2011.48"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2018.36.15_suppl.e21626"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/prp2.214"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms221910725"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/14656566.2022.2050215"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232214191"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2020.01.001"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/lsm.20860"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/17425247.2023.2152002"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1080\/10717544.2018.1534896"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1080\/10717544.2021.1933649"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/lsm.23504"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics14081537"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/lsm.23322"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2017.01.030"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/lsm.23323"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2020.01.032"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/lsm.23013"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10103-017-2168-z"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1524-4725.2012.02576.x"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/lsm.23558"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1080\/10717544.2019.1574937"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-10-2745"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.2174\/1568026622666220902104906"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-47988-8"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/lsm.23406"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncoscience.80"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1080\/17425247.2017.1260119"}],"container-title":["Lasers in Surgery and Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/lsm.23766","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,24]],"date-time":"2024-04-24T03:19:52Z","timestamp":1713928792000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/lsm.23766"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,4]]},"references-count":36,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,3]]}},"alternative-id":["10.1002\/lsm.23766"],"URL":"https:\/\/doi.org\/10.1002\/lsm.23766","archive":["Portico"],"relation":{},"ISSN":["0196-8092","1096-9101"],"issn-type":[{"value":"0196-8092","type":"print"},{"value":"1096-9101","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,4]]},"assertion":[{"value":"2023-12-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-04","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}