title: Impact of rhenium-188, gemcitabine, and 5-fluorouracil on cholangiocellular carcinoma cells: an in vitro study.
abstract: The purpose of this study was to compare the beneficial effects of radioactive stents and radioactive stents plus additional chemotherapy in the palliative treatment of cholangiocellular carcinomas. Cholangiocellular carcinoma cells (TFK-1 cells) were treated either with 8 Gy (RTB group) or 16 Gy (RTA group) (188)Re or with (188)Re irradiation (8 Gy) combined with either gemcitabine (8 Gy/Gem) or 5-fluorouracil (8 Gy/5-FU) at a dosage of 20 microg/ml medium for 4 days and subsequently compared with an untreated control group. Proliferation kinetics were assessed on days 4, 7, 11, 18, 25, and 32. Colony formation assays were performed on days 7, 18, and 32 and cell cycle distribution was examined on days 4, 7, 11, 15, 25, and 39. Cell proliferation kinetics showed the lowest cell numbers in the 8 Gy/5-FU group (control, 15,390,000; RTA group, 8,394,000; RTB group, 5,609,000; 8 Gy/Gem group, 423,000; and 8 Gy/5-FU group, 297,667). In contrast, clonogenic activity on day 32 was lower in the 8 Gy/Gem group (control, 29.3 colonies; RTB group, 23.1 colonies; 8 Gy/5-FU group, 21.5 colonies; 8 Gy/Gem, 3.3 colonies; and even augmented in the RTA group, with 37.7 colonies). Cell cycle distribution showed similar curves for all groups on slightly different levels except for the 8 Gy/5-FU group, which showed a relatively augmented percentage of cells on day 7 in the G2 M cycle phase and on day 4 in the S phase. In conclusion, irradiation (8 Gy) with (188)Re administered, e.g., via coated stents, combined with Gem could be a valid option for the treatment of CCCs.
authors.affiliation: Department of Diagnostic Radiology, University Hospital Tübingen, Hoppe-Seyler-Str. 3, 72076, Tübingen, Germany. Benjamin.wiesinger@med.uni-tuebingen.de
authors.forename: Benjamin
authors.initials: B
authors.lastname: Wiesinger
authors.forename: Emese
authors.initials: E
authors.lastname: Farkas
authors.forename: Rainer
authors.initials: R
authors.lastname: Kehlbach
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Bantleon
authors.forename: Matthias
authors.initials: M
authors.lastname: Werner
authors.forename: Jakub
authors.initials: J
authors.lastname: Wiskirchen
mesh_terms: D000704:Analysis of Variance; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D002453:Cell Cycle; D018281:Cholangiocarcinoma / Q000188:drug therapy* / Q000532:radiotherapy*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005434:Flow Cytometry; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D010166:Palliative Care; D011868:Radioisotopes / Q000494:pharmacology*; D012211:Rhenium / Q000494:pharmacology*; D015607:Stents; D014407:Tumor Cells, Cultured; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D011868:Radioisotopes; D003841:Deoxycytidine; D012211:Rhenium; D005472:Fluorouracil; D000093542:Gemcitabine