title: Photodynamic therapy using methylene blue in lung adenocarcinoma xenograft and hamster cheek pouch induced squamous cell carcinoma.
abstract: BACKGROUND
  Photodynamic therapy (PDT) is used to treat early proximal bronchial cancer during a flexible bronchoscopy. The technique relies on the excitation of a photosensitizer by an appropriate wavelength, which is delivered into the bronchus in close contact with the tumor.
  
  
  OBJECTIVE
  To assess methylene blue (MB) as a PDT agent for the treatment of respiratory tract cancer in animal models.
  
  
  METHODS
  MB-induced PDT was performed on 7 subcutaneous NCI-H460 lung adenocarcinoma xenografts in nude mice and 9 induced squamous cell cancer in the hamster cheek pouch model. In mice, PDT was carried out on right-sided tumors after intratumoral injection of methylene blue 1% (w/v) and illumination at 630nm at 200J/cm (Diomed PDT 630), with the left tumor used as control (illumination alone or MB alone). The tumoral volume was assessed before and 15 days after PDT.
  
  
  RESULTS
  Fourteen xenografts were treated in mice, including seven treated with MB-PDT, producing a 52% mean tumor volume regression (1568mm(3)vs. 544mm(3)) compared to seven control cases in which tumor volume increased (p=0.007; Mann-Whitney test). Nine cheek pouch induced carcinomas were treated in the hamster group, with a mean volume decrease of 85.8% (from 44.8% to 100%) (initial mean volume=210mm(3)vs. post PDT mean volume=97mm(3)). Histology analysis showed 4/9 complete responses.
  
  
  CONCLUSIONS
  Intratumoral MB appears efficient as PDT agent for cancer treatment in animal models. Further studies are needed to assess the safety and efficacy of MB-associated PDT for the treatment of lung cancer in humans.
authors.affiliation: Laboratoire Quant.I.F-LITIS EA 4108 & IRIB, Rouen University, F-76000 Rouen, France.
authors.forename: Bérengère
authors.initials: B
authors.lastname: Obstoy
authors.affiliation: Laboratoire Quant.I.F-LITIS EA 4108 & IRIB, Rouen University, F-76000 Rouen, France; Clinique Pneumologique & CIC INSERM U1404, Rouen University Hospital, F-76031 Rouen, France. Electronic address: mathieu.salaun@univ-rouen.fr.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Salaun
authors.affiliation: Laboratoire Quant.I.F-LITIS EA 4108 & IRIB, Rouen University, F-76000 Rouen, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Bohn
authors.affiliation: Department of Cytology & Pathology, H. Becquerel Cancer Center, Rouen, France.
authors.forename: Liana
authors.initials: L
authors.lastname: Veresezan
authors.affiliation: Laboratoire INSERM U614 & IRIB, Rouen University, F-76000 Rouen, France.
authors.forename: Richard
authors.initials: R
authors.lastname: Sesboué
authors.affiliation: Laboratoire Quant.I.F-LITIS EA 4108 & IRIB, Rouen University, F-76000 Rouen, France; Clinique Pneumologique & CIC INSERM U1404, Rouen University Hospital, F-76031 Rouen, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Thiberville
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D008027:Light; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008751:Methylene Blue / Q000008:administration & dosage*; D051379:Mice; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects / Q000528:radiation effects
chemical_list: D017319:Photosensitizing Agents; D008751:Methylene Blue
keywords: Heller model; Lung cancer; Methylene blue; Photodynamic therapy; Xenograft