title: Interaction of radiation and pemetrexed on a human malignant mesothelioma cell line in vitro.
abstract: OBJECTIVE
  To investigate the interaction of the cytotoxic activity of the combination of pemetrexed and radiation in a human mesothelioma cell line.
  
  
  METHODS
  The toxic effects of treatment with radiation and/or pemetrexed (PEM) on NCI-H28 cells were assessed by clonogenic assay. TUNEL/DAPI staining was used to measure the apoptosis index (AI). Thymidylate synthase (TS) protein expression was measured by Western blotting.
  
  
  RESULTS
  The D0 value of the combination treatment was lower than that for radiation, indicating its addition resulted in the synergistic effects with radiation. An increase in AI was observed with the combination compared with that observed after PEM alone. Radiation induced a time-dependent decrease in TS expression. Increased TS expression was observed after PEM, but the combination treatment decreased TS expression.
  
  
  CONCLUSIONS
  Treatment with pemetrexed in combination with radiation has a supra-additive effect, partially due to the synergistic induction of apoptosis, which may be due to TS suppression, by the irradiation enhancing the effect of pemetrexed.
authors.affiliation: Department of Radiation Oncology, Gunma University, Graduate School of Medicine, 3-39-22, Showa-machi, Maebashi, Gunma 371-8511, Japan. daisakuy@med.gunma-u.ac.jp
authors.forename: Daisaku
authors.initials: D
authors.lastname: Yoshida
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ebara
authors.forename: Yumi
authors.initials: Y
authors.lastname: Sato
authors.forename: Takuya
authors.initials: T
authors.lastname: Kaminuma
authors.forename: Takeo
authors.initials: T
authors.lastname: Takahashi
authors.forename: Takayuki
authors.initials: T
authors.lastname: Asao
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakano
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D005971:Glutamates / Q000627:therapeutic use*; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D066298:In Vitro Techniques; D008654:Mesothelioma / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy; D000068437:Pemetrexed; D011836:Radiation Tolerance; D011878:Radiotherapy
chemical_list: D000970:Antineoplastic Agents; D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine