title: Hypericin-mediated photodynamic therapy of pituitary tumors: preclinical study in a GH4C1 rat tumor model.
abstract: OBJECTIVE
  Hypericin-mediated photodynamic therapy (PDT) is receiving greater interest as a potential treatment for a variety of tumors and nonmalignant disorders. PDT involves systemic administration of a photosensitizer that selectively accumulates within tumor tissue followed by focal light activation. In the presence of molecular oxygen, a photochemical reaction generates a reactive oxygen species that induces apoptosis in target cells. The purpose of this preclinical study was to evaluate the efficacy of hypericin-mediated PDT for treatment of pituitary adenoma in a rodent model.
  
  
  METHODS
  Wistar-Furth rats were implanted with a pituitary adenoma rat cell line, GH4C1. Tumor masses were allowed to develop over 28 days; rats with tumors of comparable sizes were then assigned to three treatment groups: control (neither hypericin nor light); light only; and hypericin and light. Hypericin was administered in four doses (1 mg/kg) at 28-h intervals prior to light exposure, wherein those rats treated with light were exposed to a light source four hours after the last hypericin dose. Tumor size was measured up to 12 days after treatment.
  
  
  RESULTS
  Over the short interval examined, hypericin-mediated PDT was not effective against large tumors greater than 1 cm(3), but this treatment significantly slowed tumor growth for tumors less than 1 cm(3). Histological evaluation and TUNEL assay of the treated tumor identified apoptotic clusters on the periphery of the PDT-treated specimens.
  
  
  CONCLUSIONS
  Hypericin-mediated PDT shows promise in its effectiveness in the treatment of residual small tumor rests.
authors.affiliation: Department of Neurosurgery, University of Utah, 175 N. Medical Drive East, Salt Lake City, UT 84132, USA.
authors.forename: Chad D
authors.initials: CD
authors.lastname: Cole
authors.forename: James K
authors.initials: JK
authors.lastname: Liu
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Sheng
authors.forename: Steven S
authors.initials: SS
authors.lastname: Chin
authors.forename: Meic H
authors.initials: MH
authors.lastname: Schmidt
authors.forename: Martin H
authors.initials: MH
authors.lastname: Weiss
authors.forename: William T
authors.initials: WT
authors.lastname: Couldwell
mesh_terms: D000818:Animals; D000873:Anthracenes; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D020287:In Situ Nick-End Labeling; D010569:Perylene / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010778:Photochemotherapy; D010911:Pituitary Neoplasms / Q000188:drug therapy*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000873:Anthracenes; D011838:Radiation-Sensitizing Agents; D010569:Perylene; C004965:hypericin