title: Sensitizer drugs for the treatment of temozolomide-resistant glioblastoma.
abstract: OBJECTIVE
  Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor. Despite maximal cytoreductive surgery followed by chemoradiotherapy the prognosis is still poor. Although surgery and radiotherapy may have reached maximal effectiveness, chemotherapy has the potential to improve survival. The aim of this study was to evaluate in vitro the antitumor efficacy of tamoxifen (TAM), raloxifen (RAL), pyrimethamine (PYR) and alphanizomenon flos-aquae (AFA) in combination with temozolomide (TMZ) plus ionizing radiation against cultured glioblastoma stem-like cells and primary glioblastoma cells , as possible way to increase the treatment options in patients with therapy-refractory GBM.
  
  
  METHODS
  Stem-like tumor cells and glioblastoma cells isolated from two GBM biopsies were established by cell proliferation assays. TAM, RAL, PYR and AFA were added prior to TMZ and ionizing irradiation.
  
  
  RESULTS
  All tested drugs enhanced the cytotoxic effect of TMZ and sensitized cancer cells to radiotherapy as demonstrated by MTT assay and different staining reagents (TMRE, Hoechst dye and Annexin V) used for monitoring of several events in apoptosis.
  
  
  CONCLUSIONS
  The administration of certain selective estrogen receptor modulators (SERMs) (TAM and RAL), PYR and AFA before conventional postoperative chemo radiotherapy for glioblastoma might increase therapy efficiency compared to standard oncological treatment. These results need to be extended in vivo on laboratory animals in order to test the encouraging results obtained in vitro.
authors.affiliation: Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania.
authors.forename: Adriana
authors.initials: A
authors.lastname: Baritchii
authors.forename: Anca
authors.initials: A
authors.lastname: Jurj
authors.forename: Olga
authors.initials: O
authors.lastname: Soritau
authors.forename: Ciprian
authors.initials: C
authors.lastname: Tomuleasa
authors.forename: Layos
authors.initials: L
authors.lastname: Raduly
authors.forename: Oana
authors.initials: O
authors.lastname: Zanoaga
authors.forename: Dana
authors.initials: D
authors.lastname: Cernea
authors.forename: Cornelia
authors.initials: C
authors.lastname: Braicu
authors.forename: Ioana
authors.initials: I
authors.lastname: Neagoe
authors.forename: Ioan
authors.initials: I
authors.lastname: Stefan Florian
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D059248:Chemoradiotherapy; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D005909:Glioblastoma / Q000473:pathology / Q000628:therapy*; D006801:Humans; D000077204:Temozolomide
chemical_list: D000970:Antineoplastic Agents; D003606:Dacarbazine; D000077204:Temozolomide