title: Role of vitamin D(3) as a sensitizer to cryoablation in a murine prostate cancer model: preliminary in vivo study.
abstract: OBJECTIVE
  Calcitriol has been reported to have antitumor efficacy in several cancers. In this study, we hypothesized that calcitriol may potentially function as a cryosensitizer that can enhance cryoablation, and we investigated several molecular marker changes in a murine model of prostate cancer.
  
  
  METHODS
  Murine prostate tumors (RM-9) were grown in male C57BL/6J mice subcutaneously with neoadjuvant intratumoral injection of calcitriol followed by cryoablation. The microenvironmental changes after cryoablation alone and in combination with calcitriol were analyzed in a comparative fashion using immunohistochemistry and Western blot analyses.
  
  
  RESULTS
  Both cryoablation and the combination group could suppress tumor growth after treatment compared with the control. At final pathologic assessment, a larger necrotic area was seen in the combination group (P = .026). Although microvessel density (CD31) and the area of hypoxia (pimonidazole) was not different between the control and combination groups, cell proliferation (Ki-67) significantly decreased in the combination treatment (P = .035). In Western blot analyses, several markers for apoptosis were expressed significantly higher with the combination treatment.
  
  
  CONCLUSIONS
  The synergistic effect of calcitriol with cryoablation was demonstrated because of enhanced antitumor efficacy by increasing necrosis and apoptosis and reduced cell proliferation. This study suggests that calcitriol is a potentially applicable reagent as a freeze sensitizer to cryoablation.
authors.affiliation: Duke Prostate Center and Division of Urologic Surgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Masaki
authors.initials: M
authors.lastname: Kimura
authors.forename: Zahid
authors.initials: Z
authors.lastname: Rabbani
authors.forename: Vladimir
authors.initials: V
authors.lastname: Mouraviev
authors.forename: Matvey
authors.initials: M
authors.lastname: Tsivian
authors.forename: Jorge
authors.initials: J
authors.lastname: Caso
authors.forename: Takefumi
authors.initials: T
authors.lastname: Satoh
authors.forename: Shiro
authors.initials: S
authors.lastname: Baba
authors.forename: Zeljko
authors.initials: Z
authors.lastname: Vujaskovic
authors.forename: John M
authors.initials: JM
authors.lastname: Baust
authors.forename: John G
authors.initials: JG
authors.lastname: Baust
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Polascik
mesh_terms: D000818:Animals; D002762:Cholecalciferol / Q000494:pharmacology*; D003452:Cryosurgery / Q000379:methods*; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011300:Preoperative Care; D011471:Prostatic Neoplasms / Q000601:surgery*; D014815:Vitamins / Q000494:pharmacology*
chemical_list: D014815:Vitamins; D002762:Cholecalciferol