title: Cinacalcet induces apoptosis in parathyroid cells in patients with secondary hyperparathyroidism: histological and cytological analyses.
abstract: OBJECTIVE
  Previous studies reported a reduction in parathyroid gland volume during treatment with cinacalcet in patients with secondary hyperparathyroidism (SHPT). However, it remains to be determined whether cinacalcet accelerates apoptosis of hyperplastic parathyroid cells in these patients.
  
  
  METHODS
  The study subjects were 16 hemodialysis patients who had undergone parathyroidectomy for severe SHPT. We compared the expression of the apoptotic marker TUNEL and the proliferative marker Ki67 by immunohistochemistry and the expression of CYP27B1 by quantitative real-time PCR in hyperplastic parathyroid glands from patients treated with cinacalcet (cinacalcet group; n = 8) and those not treated with cinacalcet (non-cinacalcet group; n = 8). We also examined the effect of cinacalcet on parathyroid cell death in in vitro cell culture with TUNEL staining, using parathyroid cells from SHPT patients.
  
  
  RESULTS
  Compared with the non-cinacalcet group, the expression of TUNEL was significantly increased but was accompanied with significantly increased Ki67 expression in the parathyroid glands from the cinacalcet group. In vitro examination showed dose- and time-dependent increases of apoptotic cells by adding cinacalcet into culture medium. We also found that the expression of CYP27B1 showed a three-fold increase in glands from the cinacalcet group compared to that of the non-cinacalcet group.
  
  
  CONCLUSIONS
  Our data suggest that cinacalcet induces apoptosis of human parathyroid cells, but this effect may be overcome by more aggressive proliferation of parathyroid cells in patients with severe, cinacalcet-resistant SHPT.
authors: Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, Isehara, Japan.
authors: Ryoko
authors: R
authors: Tatsumi
authors: Hirotaka
authors: H
authors: Komaba
authors: Genta
authors: G
authors: Kanai
authors: Takayo
authors: T
authors: Miyakogawa
authors: Kaichiro
authors: K
authors: Sawada
authors: Takatoshi
authors: T
authors: Kakuta
authors: Masafumi
authors: M
authors: Fukagawa
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D000069449:Cinacalcet; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000009:adverse effects*; D010280:Parathyroid Glands / Q000187:drug effects* / Q000473:pathology*
chemical_list: D009281:Naphthalenes; D000069449:Cinacalcet