Department of Immunology, Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
J Invest Dermatol. 2012 Apr;132(4):1263-71. doi: 10.1038/jid.2011.418. Epub 2011 Dec 22.
Skin cancer is the most prevalent cancer worldwide and is primarily caused by chronic UV exposure. Here, we describe the topical field-directed treatment of SKH1/hr mice with UVB-damaged skin with ingenol mebutate, a new topical drug shown to be effective for the treatment of actinic keratosis (AK). Application of 0.05% ingenol mebutate gel to photo-damaged skin resulted in a ≈70% reduction in the number of skin lesions that subsequently emerged compared with placebo treatment. Ingenol mebutate treatment also reduced the number of mutant p53 keratinocyte patches by ≈70%. The treatment resulted in epidermal cell death, acute inflammation, recruitment of neutrophils, hemorrhage, and eschar formation, all of which resolved over several weeks. Ingenol mebutate field-directed treatment might thus find utility in the removal of subclinical precancerous cells from UV-damaged skin. Field-directed treatment may be particularly suitable for patients who have AKs surrounded by UV-damaged skin.
皮肤癌是全球最常见的癌症，主要由慢性紫外线暴露引起。在这里，我们描述了用 ingenol mebutate 对 SKH1/hr 小鼠进行紫外线损伤皮肤的局部定向治疗， ingenol mebutate 是一种新的局部药物，已被证明对光化性角化病 (AK) 的治疗有效。将 0.05% ingenol mebutate 凝胶应用于光损伤皮肤，与安慰剂治疗相比，随后出现的皮肤损伤数量减少了约 70%。 ingenol mebutate 治疗还减少了约 70%的突变 p53 角质形成细胞斑块。该治疗导致表皮细胞死亡、急性炎症、中性粒细胞募集、出血和焦痂形成，所有这些都在数周内得到解决。因此， ingenol mebutate 局部定向治疗可能有助于从紫外线损伤的皮肤中去除亚临床癌前细胞。局部定向治疗可能特别适合周围有紫外线损伤皮肤的 AK 患者。
