title: The therapeutic efficacy of S-1 against orthotopically implanted human pleural mesothelioma cells in severe combined immunodeficient mice.
abstract: OBJECTIVE
  Malignant pleural mesothelioma (MPM) is a highly lethal neoplasm. S-1 has been developed as a novel oral antineoplastic agent based on the modulation of 5-fluorouracil (5-FU) bioactivity. This study was conducted to investigate the preclinical therapeutic effect of S-1 on MPM.
  
  
  METHODS
  We used three human MPM cell lines, Y-MESO-14, NCI-H290 and MSTO-211H. In vitro proliferation of human MPM cells was determined by MTT assay. Human MPM cells were orthotopically implanted into thoracic cavity of SCID mice. Tumor-bearing mice were treated with S-1 or vehicle.
  
  
  RESULTS
  The combination of 5-FU and 5-chloro-2,4-dihydroxypyridine (CDHP) was more effective than 5-FU alone in inhibiting MPM cell proliferation in vitro. This combination was most effective in Y-MESO-14 cells, which co-expressed high protein level of dihydropyrimidine dehydrogenase (DPD) and thymidine phosphorylase (TP). In vivo data showed that treatment with S-1 significantly reduced thoracic tumors and pleural effusion produced by Y-MESO-14 cells. Moreover, treatment with S-1 prolonged the survival of Y-MESO-14 cell-bearing SCID mice.
  
  
  CONCLUSIONS
  We demonstrated that S-1 was effective for inhibiting the proliferation of MPM cells, particularly with both DPD and TP expressions, suggesting that S-1 might be therapeutically effective for control of MPM.
authors.affiliation: Department of Medical Oncology, University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Trung The
authors.initials: TT
authors.lastname: Van
authors.forename: Masaki
authors.initials: M
authors.lastname: Hanibuchi
authors.forename: Soji
authors.initials: S
authors.lastname: Kakiuchi
authors.forename: Seidai
authors.initials: S
authors.lastname: Sato
authors.forename: Takuya
authors.initials: T
authors.lastname: Kuramoto
authors.forename: Hisatsugu
authors.initials: H
authors.lastname: Goto
authors.forename: Atsushi
authors.initials: A
authors.lastname: Mitsuhashi
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Nishioka
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Akiyama
authors.forename: Saburo
authors.initials: S
authors.lastname: Sone
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000037:antagonists & inhibitors / Q000378:metabolism; D004338:Drug Combinations; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D010094:Oxonic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D010430:Pentosyltransferases / Q000037:antagonists & inhibitors; D010997:Pleural Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011725:Pyridines / Q000008:administration & dosage / Q000627:therapeutic use*; D011897:Random Allocation; D016019:Survival Analysis; D005641:Tegafur / Q000008:administration & dosage / Q000627:therapeutic use*; D013939:Thymidine Phosphorylase / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D009363:Neoplasm Proteins; D011725:Pyridines; C079198:S 1 (combination); D005641:Tegafur; C489337:potassium oxonate; D010094:Oxonic Acid; D042943:Dihydrouracil Dehydrogenase (NADP); D010430:Pentosyltransferases; C022500:pyrimidine phosphoribosyltransferase; C543750:TYMP protein, human; D013939:Thymidine Phosphorylase; C104201:gimeracil