title: Topical methotrexate pretreatment enhances the therapeutic effect of topical 5-aminolevulinic acid-mediated photodynamic therapy on hamster buccal pouch precancers.
abstract: OBJECTIVE
  Topical 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) is effective for treatment of human oral precancerous lesions. This animal study aimed to assess whether topical methotrexate (MTX) pretreatment could enhance the therapeutic effect of topical ALA-PDT on hamster buccal pouch precancerous lesions.
  
  
  METHODS
  Twenty hamster buccal pouch precancerous lesions were treated with either topical ALA-PDT with topical MTX pretreatment (topical MTX-ALA-PDT group, n = 10) or topical ALA-PDT alone (topical ALA-PDT group, n = 10). The intracellular protoporphyrin IX (PpIX) level in another 12 precancerous lesions (n = 6 for either the topical MTX-ALA or topical ALA group) was monitored by fluorescence spectroscopy.
  
  
  RESULTS
  The intracellular PpIX reached its peak level in precancerous lesions 6.5 hours and 2.5 hours after topical ALA application for the topical MTX-ALA group (5.63-fold higher in the lesion than in the normal mucosa) and topical ALA group (2.42-fold higher in the lesion than in the normal mucosa), respectively. The complete response rate of precancerous lesions was 80% for the topical MTX-ALA-PDT group and 70% for the topical ALA-PDT group. In addition, the topical MTX-ALA-PDT group required a significantly lower mean treatment number (2.1 ± 0.6) to achieve complete response than the topical ALA-PDT group (4.4 ± 1.3, p < 0.001)). Moreover, the topical MTX-ALA-PDT group had a lower recurrence rate (12.5%) than the topical ALA-PDT group (28.6%).
  
  
  CONCLUSIONS
  We conclude that topical MTX-pretreatment can increase intracellular PpIX production in hamster buccal pouch precancerous lesions and significantly improves the outcomes of the precancerous lesions treated with topical ALA-PDT.
authors.affiliation: Department of Bioscience Technology, Chung Yuan Christian University, Taoyuan, Taiwan.
authors.forename: Deng-Fu
authors.initials: DF
authors.lastname: Yang
authors.affiliation: Department of Life Science, Tzu Chi University, Hualien, Taiwan.
authors.forename: Jeng-Woei
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital, College of Medicine, Taipei, Taiwan.
authors.forename: Hsin-Ming
authors.initials: HM
authors.lastname: Chen
authors.affiliation: Department of Bioscience Technology, Chung Yuan Christian University, Taoyuan, Taiwan; Center for Nanotechnology, Chung Yuan Christian University, Taoyuan, Taiwan; Center of Biomedical Technology, Chung Yuan Christian University, Taoyuan, Taiwan. Electronic address: ivyhsu@cycu.edu.tw.
authors.forename: Yih-Chih
authors.initials: YC
authors.lastname: Hsu
mesh_terms: D000287:Administration, Topical; D000622:Aminolevulinic Acid / Q000008:administration & dosage*; D000818:Animals; D006224:Cricetinae; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D009061:Mouth Mucosa / Q000187:drug effects / Q000473:pathology*; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009374:Neoplasms, Experimental; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage; D011230:Precancerous Conditions / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D017319:Photosensitizing Agents; D000622:Aminolevulinic Acid; D008727:Methotrexate
keywords: 5-aminolevulinic acid; hamster buccal pouch precancer; methotrexate; oral precancerous lesions; topical photodynamic therapy