title: Photodynamic Therapy Using Novel Glucose-conjugated Chlorin Increases Apoptosis of Cholangiocellular Carcinoma in Comparison with Talaporfin Sodium.
abstract: Photodynamic therapy (PDT) is an effective laser treatment for locally treating advanced bile duct carcinoma (BDC). The study's objective was to evaluate the increased cytocidal effect by apoptotic PDT using a novel photosensitizer, glucose-conjugated chlorin, by irradiation of light-emitting diode laser (G-PDT) in comparison with conventional PDT using talaporfin sodium (T-PDT).
  
  
  
  The cytocidal effect of G-PDT was compared to that of T-PDT as a control. Tumor viability was determined by an in vitro MTS assay. The percentage of apoptosis-positive cells was examined by triple stain flow cytometry (annexin V, ethidium homodimer III and Hoechst 33342) in the BDC cell line (NOZ cell) in vitro. The change in transplanted tumor volume in vivo (4-week-old male BALB/c mice) was examined 7 days after PDT.
  
  
  
  Cell death was induced in a light dose-dependent manner by PDT. The laser power was set at 5 Jules/cm(2) to obtain half maximal inhibitory concentration (IC50) in T-PDT and G-PDT and the concentration of photosensitivity for G-PDT (2.02 μg/ml) was lower than that for T-PDT (4.14 μg/ml). Both T-PDT and G-PDT showed increased induction rates in comparison to the light only or G-chlorin only. Furthermore, the rate of apoptosis in the G-PDT (92.6%) was increased in comparison to that in the T-PDT (38.9%). The increased rates of tumor volume during the 7 days in both the G-PDT and T-PDT groups were significantly lower than that in the non-PDT group (p<0.01). At day 7, the increased rates of tumor volume in the G-PDT group were significantly lower than that in the T-PDT group (p<0.05).
  
  
  
  The new G-PDT treatment showed a high prevalence of apoptosis and inhibition of tumor growth in treatment of BDC cells.
authors.affiliation: Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Goushi
authors.initials: G
authors.lastname: Murakami
authors.affiliation: Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan Division of Hepato-biliary-pancreas Surgery, Department of Surgery, University of Miyazaki Faculty of Medicine, Miyazaki, Japan a_nanashima@med.miyazaki-u.ac.jp.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nanashima
authors.affiliation: Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nonaka
authors.affiliation: Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Tominaga
authors.affiliation: Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Kouki
authors.initials: K
authors.lastname: Wakata
authors.affiliation: Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Yorihisa
authors.initials: Y
authors.lastname: Sumida
authors.affiliation: Research Institute of Natural Sciences, Okayama University of Science, Okayama, Japan.
authors.forename: Haruo
authors.initials: H
authors.lastname: Akashi
authors.affiliation: Preeminent Medical Photonics Education and Research Center, Hamamatsu University School of Medicine, Shizuoka, Japan.
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Okazaki
authors.affiliation: Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kataoka
authors.affiliation: Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nagayasu
mesh_terms: D000818:Animals; D017209:Apoptosis; D001650:Bile Duct Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002470:Cell Survival; D018281:Cholangiocarcinoma / Q000188:drug therapy*; D005434:Flow Cytometry; D005947:Glucose / Q000737:chemistry*; D006801:Humans; D020287:In Situ Nick-End Labeling; D007834:Lasers; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010778:Photochemotherapy / Q000379:methods; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011166:Porphyrins / Q000737:chemistry* / Q000494:pharmacology*; D015995:Prevalence
chemical_list: D017319:Photosensitizing Agents; D011166:Porphyrins; C006969:chlorin; D005947:Glucose; C053434:Talaporfin
keywords: Cholangiocellular carcinoma; apoptosis; glucose-conjugated chlorin; light emitting diode laser; photodynamic therapy