title: Expression of ferrochelatase has a strong correlation in protoporphyrin IX accumulation with photodynamic detection of bladder cancer.
abstract: BACKGROUND
  The mechanism underlying the increased levels of protoporphyrin IX in bladder cancer remains unclear. Here, we focus on proteins associated with protoporphyrin IX accumulation in bladder cancer cells and investigate the protein that plays a key role in increased protoporphyrin IX accumulation in bladder cancer cells.
  
  
  METHODS
  Western blotting was used to determine the expression of peptide transporter 1, hydroxymethylbilane synthase, ferrochelatase, ATP-binding cassette 2, and heme oxygenase-1 in bladder cancer cell line cells. We evaluated the correlation between the expression of each protein and accumulated protoporphyrin IX in these cells using Pearson's correlation analysis. Immunohistochemistry was used to estimate the expression of the same five proteins in samples from 75 patients who underwent transurethral resection of bladder tumors. The correlation between the expression of each protein in cells from resected bladder specimens and accumulated protoporphyrin IX in bladder cancer cells in voided urine was evaluated using Pearson's correlation analysis.
  
  
  RESULTS
  The expression of ferrochelatase showed a significant negative correlation with protoporphyrin IX accumulation in vitro (p=0.04). The expression of peptide transporter 1 (p<0.01, R=0.39), heme oxygenase-1 (p<0.01, R=0.33), and ferrochelatase (p<0.01, R=0.75) in resected bladder specimens by immunohistochemistry was correlated with protoporphyrin IX accumulation in bladder cancer cells in voided urine. On multivariate analysis, the expression of ferrochelatase (p=0.03) was significant factors to predict positive 5-aminolevulinic acid-induced fluorescent cytology.
  
  
  CONCLUSIONS
  The expression of ferrochelatase has a strong correlation in protoporphyrin IX accumulation with photodynamic detection of bladder cancer.
authors.affiliation: Department of Urology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Nakai
authors.affiliation: Department of Urology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Tatsumi
authors.affiliation: Department of Urology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan.
authors.forename: Makito
authors.initials: M
authors.lastname: Miyake
authors.affiliation: Department of Urology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Anai
authors.affiliation: Department of Urology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan.
authors.forename: Masaomi
authors.initials: M
authors.lastname: Kuwada
authors.affiliation: Department of Urology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan.
authors.forename: Sayuri
authors.initials: S
authors.lastname: Onishi
authors.affiliation: Department of Urology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan.
authors.forename: Yoshitomo
authors.initials: Y
authors.lastname: Chihara
authors.affiliation: Department of Urology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan.
authors.forename: Nobumichi
authors.initials: N
authors.lastname: Tanaka
authors.affiliation: Department of Urology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Hirao
authors.affiliation: Department of Urology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan. Electronic address: kiyokun@naramed-u.ac.jp.
authors.forename: Kiyohide
authors.initials: K
authors.lastname: Fujimoto
mesh_terms: D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003558:Cystoscopy / Q000379:methods*; D005294:Ferrochelatase / Q000378:metabolism*; D006801:Humans; D008856:Microscopy, Fluorescence / Q000379:methods; D057054:Molecular Imaging / Q000379:methods; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D011524:Protoporphyrins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX; D005294:Ferrochelatase
keywords: 5-Aminolevulinic acid; Ferrochelatase; Protoporphyrin IX