gimeracil and Mesothelioma

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.. 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.. 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.. 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.

Topics: Animals; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Cell Line, Tumor; Dihydrouracil Dehydrogenase (NADP); Drug Combinations; Enzyme Inhibitors; Humans; Male; Mesothelioma; Mice; Mice, SCID; Neoplasm Proteins; Oxonic Acid; Pentosyltransferases; Pleural Neoplasms; Pyridines; Random Allocation; Survival Analysis; Tegafur; Thymidine Phosphorylase; Tumor Burden; Xenograft Model Antitumor Assays