title: miR-34a expression, cell cycle arrest and cell death of malignant mesothelioma cells upon treatment with radiation, docetaxel or combination treatment.
abstract: OBJECTIVE
  Malignant mesothelioma (MM) is a highly aggressive tumour related to asbestos exposure. Histopathologically, the tumour is classified as epithelial, sarcomatoid or biphasic. To date, MM is still an incurable disease.
  
  
  METHODS
  To evaluate treatment strategies on MM cells, the effects of radiotherapy, docetaxel or a combination of both on MM cells derived from the sarcomatoid type ZL34 and the epithelial type M28K were investigated. The TP53 gene, micro-RNA expression, cell cycle distribution and cell death were assessed as indicators of treatment effects.
  
  
  RESULTS
  Despite the normal TP53 gene sequences in these cell lines, radiation-induced miR-34a expression was detected only in the M28K cells. Increasing G0/G1 cell numbers were detected in irradiated M28K and ZL34 cells. There was more radiation-induced cell death in M28K compared to ZL34 cells. The highest degree of cell cycle arrest at G2 and cell death in both cell types was obtained in the presence of docetaxel. The combination of docetaxel and radiation did not show any additive effects on miR-34a expression, cell cycle arrest or cell death in either the M28K or ZL34 cells.
  
  
  CONCLUSIONS
  Microtubule formation and other related functions by docetaxel might be the most suitable treatment modulation in both sarcomatoid and epithelial types of MM.
authors.affiliation: Department of Oncology, Rudbeck Laboratory, Uppsala University Hospital, Uppsala, Sweden.
authors.forename: Taha
authors.initials: T
authors.lastname: Ghawanmeh
authors.forename: Ulf
authors.initials: U
authors.lastname: Thunberg
authors.forename: Juan
authors.initials: J
authors.lastname: Castro
authors.forename: Fiona
authors.initials: F
authors.lastname: Murray
authors.forename: Nongnit
authors.initials: N
authors.lastname: Laytragoon-Lewin
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects* / Q000235:genetics / Q000528:radiation effects*; D016923:Cell Death / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy / Q000379:methods; D000077143:Docetaxel; D006801:Humans; D008654:Mesothelioma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D043823:Taxoids / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D011838:Radiation-Sensitizing Agents; C495901:TP53 protein, human; D043823:Taxoids; D016159:Tumor Suppressor Protein p53; D000077143:Docetaxel