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In 25 mice, 1 cm<jats:sup>2<\/jats:sup> skin test sites (<jats:italic>n<\/jats:italic> = 44) containing microscopic BCCs were exposed to one of three interventions: a single CO<jats:sub>2<\/jats:sub> AFL treatment (1 pulse, 40 mJ\/microbeam, wavelength 10.6 \u03bcm, 5% density, pulse rate 250 Hz, <jats:italic>n<\/jats:italic> = 12), eight topical vismodegib treatments (3.8 mg\/mL, <jats:italic>n<\/jats:italic> = 8), or combination of AFL and vismodegib treatments (<jats:italic>n<\/jats:italic> = 9). Untreated controls were included for comparison (<jats:italic>n<\/jats:italic> = 15). After 4 days, skin samples were analyzed for hedgehog gene expression (<jats:italic>Gli1<\/jats:italic>, <jats:italic>Gli2<\/jats:italic>, and <jats:italic>Ptch1<\/jats:italic>) by qPCR and vismodegib concentrations by liquid chromatography mass spectrometry (data analyzed with two-tailed <jats:italic>t<\/jats:italic>-tests and linear regression). A single treatment with AFL monotherapy significantly reduced hedgehog gene expression compared to untreated controls (<jats:italic>Gli1<\/jats:italic> 72.4% reduction, <jats:italic>p<\/jats:italic> = 0.003; <jats:italic>Gli2<\/jats:italic> 55.2%, <jats:italic>p<\/jats:italic> = 0.010; <jats:italic>Ptch1<\/jats:italic> 70.9%, <jats:italic>p<\/jats:italic> &lt; 0.001). Vismodegib treatment also reduced hedgehog gene expression (<jats:italic>Gli1<\/jats:italic> 91.6%; <jats:italic>Gli2<\/jats:italic> 83.3%; <jats:italic>Ptch1<\/jats:italic> 83.0%), significantly surpassing AFL monotherapy for two out of three genes (<jats:italic>Gli1<\/jats:italic>, <jats:italic>p<\/jats:italic> = 0.017; <jats:italic>Gli2<\/jats:italic>, <jats:italic>p<\/jats:italic> = 0.007; <jats:italic>Ptch1<\/jats:italic>, <jats:italic>p<\/jats:italic> = 0.15). AFL and vismodegib combination mirrored the effects of vismodegib monotherapy (<jats:italic>Gli1<\/jats:italic>, <jats:italic>p<\/jats:italic> = 0.424; <jats:italic>Gli2<\/jats:italic>, <jats:italic>p<\/jats:italic> = 0.289; <jats:italic>Ptch1<\/jats:italic>, <jats:italic>p<\/jats:italic> = 0.593), possibly due to comparable cutaneous vismodegib concentrations (mean \u00b1 SD, vismodegib monotherapy 850 \u00b1 475 \u00b5mol\/L; combination 1036 \u00b1 824 \u00b5mol\/L; <jats:italic>p<\/jats:italic> = 0.573). In conclusion, a single AFL treatment significantly reduced hedgehog gene expression in murine BCCs mimicking the effects of eight topical applications of vismodegib. Further studies are needed to assess whether AFL can be utilized for BCC treatment, either as monotherapy or in combination with other drugs.<\/jats:p>","DOI":"10.1007\/s10103-024-03997-1","type":"journal-article","created":{"date-parts":[[2024,2,3]],"date-time":"2024-02-03T03:01:56Z","timestamp":1706929316000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Ablative fractional laser treatment reduces hedgehog pathway gene expression in murine basal cell carcinomas"],"prefix":"10.1007","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9994-7848","authenticated-orcid":false,"given":"Kristian K\u00e5ber","family":"Pedersen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5887-630X","authenticated-orcid":false,"given":"Jonatan Riber","family":"Granborg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3653-6424","authenticated-orcid":false,"given":"Catharina Margrethe","family":"Lerche","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6068-901X","authenticated-orcid":false,"given":"Thomas","family":"Litman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4578-684X","authenticated-orcid":false,"given":"Uffe H\u00f8gh","family":"Olesen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1250-2035","authenticated-orcid":false,"given":"Merete","family":"H\u00e6dersdal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,2,3]]},"reference":[{"key":"3997_CR1","doi-asserted-by":"publisher","first-page":"890","DOI":"10.1093\/aje\/kwt073","volume":"178","author":"S Wu","year":"2013","unstructured":"Wu S, Han J, Li W-Q, Li T, Qureshi AA (2013) Basal-cell carcinoma incidence and associated risk factors in US women and men. 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