title: Temperature-dependent impact of thermal aminolaevulinic acid photodynamic therapy on apoptosis and reactive oxygen species generation in human dermal fibroblasts.
abstract: BACKGROUND
  Actinic keratoses (AKs) are generally accepted as common precursor lesions to invasive squamous cell carcinoma. Photodynamic therapy (PDT) is a common, in-office, field therapy modality used in the treatment of AKs. Clinical and laboratory observations have demonstrated that temperature modulation can affect PDT efficacy.
  
  
  OBJECTIVE
  To demonstrate thermal PDT increases apoptotic cell death, and to investigate the mechanistic role of reactive oxygen species (ROS) free radicals in an in vitro human skin fibroblast model.
  
  
  METHODS
  This study was completed using commercially available primary human skin fibroblasts treated with aminolaevulinic acid (ALA) at specific concentrations and controlled temperatures. Cell death, apoptosis and superoxide ROS levels were quantified.
  
  
  RESULTS
  We found that thermal PDT with 0·5 mmol L(-1) ALA resulted in significant temperature-dependent increases in total apoptosis and superoxide ROS generation between 33 °C and 42 °C.
  
  
  CONCLUSIONS
  Our results indicate that thermal PDT significantly increases apoptotic cell death through increased generation of superoxide ROS in a temperature-dependent manner.
authors.affiliation: Department of Dermatology, University of California at Davis, Sacramento, CA, U.S.A.|Dermatology Service, Sacramento VA Medical Center, Mather, CA, U.S.A.
authors.forename: A
authors.initials: A
authors.lastname: Mamalis
authors.affiliation: Department of Dermatology, University of California at Davis, Sacramento, CA, U.S.A.|Dermatology Service, Sacramento VA Medical Center, Mather, CA, U.S.A.
authors.forename: E
authors.initials: E
authors.lastname: Koo
authors.affiliation: Department of Dermatology, University of California at Davis, Sacramento, CA, U.S.A.
authors.forename: G D
authors.initials: GD
authors.lastname: Sckisel
authors.affiliation: Department of Dermatology, SUNY Downstate Medical Center, Brooklyn, NY, U.S.A.
authors.forename: D M
authors.initials: DM
authors.lastname: Siegel
authors.affiliation: Department of Dermatology, University of California at Davis, Sacramento, CA, U.S.A. jrjagdeo@gmail.com.|Dermatology Service, Sacramento VA Medical Center, Mather, CA, U.S.A. jrjagdeo@gmail.com.|Department of Dermatology, SUNY Downstate Medical Center, Brooklyn, NY, U.S.A. jrjagdeo@gmail.com.
authors.forename: J
authors.initials: J
authors.lastname: Jagdeo
mesh_terms: D000622:Aminolevulinic Acid / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005434:Flow Cytometry; D006358:Hot Temperature; D006801:Humans; D066298:In Vitro Techniques; D055623:Keratosis, Actinic / Q000188:drug therapy*; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012867:Skin / Q000378:metabolism
chemical_list: D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species; D000622:Aminolevulinic Acid