title: Castration therapy of prostate cancer results in downregulation of HIF-1α levels.
abstract: OBJECTIVE
  Neoadjuvant androgen deprivation in combination with radiotherapy of prostate cancer is used to improve radioresponsiveness and local tumor control. Currently, the underlying mechanism is not well understood. Because hypoxia causes resistance to radiotherapy, we wanted to test whether castration affects the degree of hypoxia in prostate cancer.
  
  
  METHODS
  In 14 patients with locally advanced prostate cancer, six to 12 prostatic needle core biopsy specimens were taken prior to castration therapy. Bilateral orchidectomy was performed in 7 patients, and 7 were treated with a GnRH-agonist (leuprorelin). After castrationm two to four prostatic core biopsy specimens were taken, and the level of hypoxia-inducible factor-1α (HIF-1α) in cancer was determined by immunofluorescence.
  
  
  RESULTS
  Among biopsy specimens taken before castration, strong HIF-1α expression (mean intensity above 30) was shown in 5 patients, weak expression (mean intensity 10-30) in 3 patients, and background levels of HIF-1α (mean intensity 0-10) in 6 patients. Downregulation of HIF-1α expression after castration was observed in all 5 patients with strong HIF-1α precastration expression. HIF-1α expression was also reduced in 2 of 3 patients with weak HIF-1α precastration expression.
  
  
  CONCLUSIONS
  Our data suggest that neoadjuvant castration decreases tumor cell hypoxia in prostate cancer, which may explain increased radiosensitivity after castration.
authors.affiliation: Department of Genetics, Microbiology and Toxicology, Stockholm University, Stockholm, Sweden.
authors.forename: Firas L T
authors.initials: FL
authors.lastname: Al-Ubaidi
authors.forename: Niklas
authors.initials: N
authors.lastname: Schultz
authors.forename: Lars
authors.initials: L
authors.lastname: Egevad
authors.forename: Torvald
authors.initials: T
authors.lastname: Granfors
authors.forename: Thomas
authors.initials: T
authors.lastname: Helleday
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001707:Biopsy, Needle; D015687:Cell Hypoxia; D015536:Down-Regulation; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis* / Q000378:metabolism; D016729:Leuprolide / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009919:Orchiectomy / Q000379:methods*; D011467:Prostate / Q000737:chemistry / Q000473:pathology; D011471:Prostatic Neoplasms / Q000737:chemistry* / Q000473:pathology / Q000601:surgery* / Q000628:therapy; D011836:Radiation Tolerance
chemical_list: D000726:Androgen Antagonists; D015415:Biomarkers; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016729:Leuprolide