title: Cellular density, a major factor involved in PDT cytotoxic responses: Study on three different lines of human retinoblastoma grafted on nude mice.
abstract: BACKGROUND
  PDT represents a very localized and non-mutagen antitumoral treatment using a photosensitive molecule (porphyrin family) light activated. The first way of cell damage is a direct one, active on the very site where ROSs have been produced. The second one is indirect by activating and transmitting the processes of cellular death signaling. In order to seek for a better characterization of the photo-biology involved in in vivo PDT and to better understand the differences on the treatment outcome, we have used three different human retinoblastomas xenografted on mice.
  
  
  METHODS
  Mice were treated according to the double targeting protocol exposed in a previous paper. One i.v. dose (0.6 mg/kg) of PS was followed by a second dose, separated by a 3 h interval (double targeting PDT). As a consequence both cancer cells and blood vessels were targeted. The treatment was repeated two times, at 4 days interval.
  
  
  RESULTS
  First of all, sodium MRI revealed qualitative differences in the sodium average content of the three retinoblastoma lines before treatment. After the PDT treatments the tumor responses were different between the lines as revealed by sodium MRI and later on by histology.
  
  
  CONCLUSIONS
  We have put into evidence that PDT is accompanied by a bystander effect that may propagate the cellular death triggered by the initial photoreaction. This effect is highly dependent on the cellular density of the tissue; therefore this factor is to be taken into account in clinical PDT protocols.
authors: Institut Curie, Bât.112, Centre Universitaire, F 91405 Orsay Cedex, France; U759 INSERM, Bât.112, Centre Universitaire, F 91405 Orsay Cedex, France; Université Paris-Sud, F 91405 Orsay Cedex, France.
authors: Carole D
authors: CD
authors: Thomas
authors: Institut Curie, Bât.112, Centre Universitaire, F 91405 Orsay Cedex, France; U759 INSERM, Bât.112, Centre Universitaire, F 91405 Orsay Cedex, France; Université Paris-Sud, F 91405 Orsay Cedex, France.
authors: Florent
authors: F
authors: Poyer
authors: Institut Curie, Bât.112, Centre Universitaire, F 91405 Orsay Cedex, France; Université Paris-Sud, F 91405 Orsay Cedex, France; UMR 176 CNRS, Bât.112, Centre Universitaire, F 91405 Orsay Cedex, France.
authors: Philippe
authors: P
authors: Maillard
authors: Clinical Pharmacy Department, Assistance Publique Hôpitaux de Paris, Hôpital Bicêtre, Hôpitaux Universitaires Paris Sud AP/HP, 78 rue du Général Leclerc, 94270, Kremlin Bicêtre, France.
authors: Benoit
authors: B
authors: Chauvin
authors: Institut Curie, Bât.112, Centre Universitaire, F 91405 Orsay Cedex, France; U759 INSERM, Bât.112, Centre Universitaire, F 91405 Orsay Cedex, France; Université Paris-Sud, F 91405 Orsay Cedex, France. Electronic address: mihaela.lupu@curie.u-psud.fr.
authors: Mihaela
authors: M
authors: Lupu
authors: Institut Curie, Bât.112, Centre Universitaire, F 91405 Orsay Cedex, France; U759 INSERM, Bât.112, Centre Universitaire, F 91405 Orsay Cedex, France; Université Paris-Sud, F 91405 Orsay Cedex, France.
authors: Joël
authors: J
authors: Mispelter
mesh_terms: D000818:Animals; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects*; D045744:Cell Line, Tumor; D006801:Humans; D008279:Magnetic Resonance Imaging; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012175:Retinoblastoma / Q000188:drug therapy*
chemical_list: D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species
keywords: Cellular density; PDT; Retinoblastoma; Sodium MRI