title: Sorafenib's inhibition of prostate cancer growth in transgenic adenocarcinoma mouse prostate mice and its differential effects on endothelial and pericyte growth during tumor angiogenesis.
abstract: OBJECTIVE
  To evaluate Sorafenib's efficacy (60 mg/kg/d per os) in preventing the transformation of high grade prostate intraepithelial neoplasia (HGPIN) into adenocarcinoma (ADC) and in inhibiting the onset and progression of poorly differentiated carcinoma (PDC) in transgenic adenocarcinoma mouse prostate (TRAMP) mice.
  
  
  METHODS
  Forty-four TRAMP mice were randomly divided into 2 groups of 22 and assigned to daily treatment by gavage with vehicle only or Sorafenib from the 10th to the 26th week of age. At 26 weeks of age the mice were killed, and their genitourinary apparatus was removed and examined by histology, immunohistochemistry and confocal microscopy.
  
  
  RESULTS
  Sorafenib reduced HGPIN growth and progression to ADC and was probably also effective in PDC inhibition. The major effect of Sorafenib was on tumor angiogenesis. Interestingly a dissociation between endothelial cells and pericytes was noted in treated PDC since inhibition of pericyte recruitment was less complete than that of endothelial cells.
  
  
  CONCLUSIONS
  Sorafenib's potent antiangiogenic action may be supposed to be exerted primarily by inhibiting endothelial proliferation and sprouting, whereas its inhibition of pericyte recruitment and maturation is less complete. These observations suggest that Sorafenib's effects could be improved by the joint employment of substances capable of interfering with the recruitment and organization of pericytes.
authors.affiliation: Department of Urology, University of Brescia, Brescia, Italy.
authors.forename: Aldo V
authors.initials: AV
authors.lastname: Bono
authors.forename: Tania
authors.initials: T
authors.lastname: Pannellini
authors.forename: Marcella
authors.initials: M
authors.lastname: Liberatore
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Montironi
authors.forename: Sergio Cosciani
authors.initials: SC
authors.lastname: Cunico
authors.forename: Liang
authors.initials: L
authors.lastname: Cheng
authors.forename: Francesco
authors.initials: F
authors.lastname: Sasso
authors.forename: Piero
authors.initials: P
authors.lastname: Musiani
authors.forename: Manuela
authors.initials: M
authors.lastname: Iezzi
mesh_terms: D000230:Adenocarcinoma / Q000098:blood supply* / Q000473:pathology / Q000517:prevention & control; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001557:Benzenesulfonates / Q000494:pharmacology*; D018450:Disease Progression; D004354:Drug Screening Assays, Antitumor; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology; D019085:Fluorescent Antibody Technique, Direct; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000517:prevention & control*; D009536:Niacinamide / Q000031:analogs & derivatives; D020286:Pericytes / Q000187:drug effects* / Q000473:pathology; D010671:Phenylurea Compounds; D019048:Prostatic Intraepithelial Neoplasia / Q000098:blood supply / Q000473:pathology / Q000517:prevention & control; D011471:Prostatic Neoplasms / Q000098:blood supply* / Q000473:pathology / Q000517:prevention & control; D011725:Pyridines / Q000494:pharmacology*; D000077157:Sorafenib; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib