title: Non-sufficient cell cycle control as possible clue for the resistance of human malignant glioma cells to clinically relevant treatment conditions.
abstract: OBJECTIVE
  Human gliomas have a catastrophic prognosis with a median survival in the range of one year even after therapeutic treatment. Relatively high resistance towards apoptotic stimuli is the characteristic feature of malignant gliomas. Since cell cycle control has been shown to be the key mechanism controlling both apoptosis and proliferation, this study focuses on DNA damage analysis and protein expression patterns of essential cell cycle regulators P53 and P21waf1/cip1 in glioma under clinically relevant therapeutic conditions.
  
  
  METHODS
  U87MG cell line, characterised by wild p53-phenotype relevant for the majority of primary malignant glioblastomas, was used. Glioma cells underwent either irradiation or temozolomide treatment alone, or combined radio/chemo treatment. DNA damage was analysed by the "Comet Assay". Expression rates of target proteins were analysed using "Western-Blot" technique.
  
  
  CONCLUSIONS
  "Comet Assay" demonstrated extensive DNA damage caused by temozolomide treatment alone and in combination with irradiation, correlating well with the low survival rate observed under these treatment conditions. In contrast, irradiation alone resulted in a relatively low DNA damage, correlating well with a high survival rate and indicating a poor therapeutic efficiency of irradiation alone. Unusually low up-regulation of P53 and P21waf1/cip1 expression patterns was produced by the hereby tested stressful conditions. A deficit in cell cycle control might be the clue to the high resistance of malignant glioma cells to established therapeutic approaches.
authors.affiliation: Department of Radiology, Friedrich-Wilhelms-University of Bonn, Bonn, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Trog
authors.forename: H
authors.initials: H
authors.lastname: Moenkemann
authors.forename: W
authors.initials: W
authors.lastname: Breipohl
authors.forename: H
authors.initials: H
authors.lastname: Schueller
authors.forename: H
authors.initials: H
authors.lastname: Schild
authors.forename: O
authors.initials: O
authors.lastname: Golubnitschaja
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002453:Cell Cycle / Q000187:drug effects* / Q000528:radiation effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003131:Combined Modality Therapy; D020552:Comet Assay; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects / Q000528:radiation effects; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000528:radiation effects*; D005910:Glioma / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D006801:Humans; D000077204:Temozolomide; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D018906:Antineoplastic Agents, Alkylating; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016159:Tumor Suppressor Protein p53; D003606:Dacarbazine; D000077204:Temozolomide