title: Re-evaluation of cytostatic therapies for meningiomas in vitro.
abstract: OBJECTIVE
  The purpose was to re-evaluate in cell culture models the therapeutic usefulness of some discussed chemotherapies or targeted therapies for meningiomas with a special emphasis on the role of the neurofibromatosis type 2 (NF2) tumor suppressor, which had been neglected so far. In addition, the study intended to evaluate a potential benefit from a treatment with drugs which are well established in other fields of medicine and have been linked recently with tumor disease by epidemiological studies.
  
  
  METHODS
  Meningioma cell lines corresponding to various subtypes and pairs of syngenic meningioma cell lines with or without shRNA-induced NF2 knockdown were analyzed for their dose-dependent response to the drugs in microtiter tetrazolium assays, BrdU assays and for selected cases in ELISAs measuring nucleosome liberation to specifically separate cell death from pure inhibition of cell proliferation.
  
  
  RESULTS
  We confirmed a moderate efficacy of hydroxyurea (HU) in clinically relevant concentrations. Under appropriate dosing, we neither detected major responses to the alkylating compound temozolomide nor to various drugs targeting membrane receptors or enzymes (tamoxifen, erlotinib, mifepristone, losartan, metformin and verapamil). Only concentrations far beyond achievable serum levels generated significant effects with the exception of losartan, which showed no effects at all. Chemosensitivity varied markedly among meningioma cell lines. Importantly, cells with NF2 loss exhibited a significantly higher induction of cell death by HU.
  
  
  CONCLUSIONS
  Alternative chemotherapeutic or targeted approaches besides HU have still to be evaluated in further studies, and the role of NF2 must be taken into account.
authors.affiliation: Department of Neuropathology, Otto-von-Guericke University, Leipziger Str. 44, 39120, Magdeburg, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Wilisch-Neumann
authors.forename: Doreen
authors.initials: D
authors.lastname: Pachow
authors.forename: Maren
authors.initials: M
authors.lastname: Wallesch
authors.forename: Astrid
authors.initials: A
authors.lastname: Petermann
authors.forename: Frank D
authors.initials: FD
authors.lastname: Böhmer
authors.forename: Elmar
authors.initials: E
authors.lastname: Kirches
authors.forename: Christian
authors.initials: C
authors.lastname: Mawrin
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D045744:Cell Line, Tumor; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D000069347:Erlotinib Hydrochloride; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology*; D019808:Losartan / Q000494:pharmacology; D008577:Meningeal Neoplasms / Q000188:drug therapy*; D008579:Meningioma / Q000188:drug therapy*; D008687:Metformin / Q000494:pharmacology; D015735:Mifepristone / Q000494:pharmacology; D025581:Neurofibromin 2 / Q000235:genetics; D011401:Promoter Regions, Genetic; D011799:Quinazolines / Q000494:pharmacology; D011836:Radiation Tolerance; D013629:Tamoxifen / Q000494:pharmacology; D000077204:Temozolomide; D025521:Tumor Suppressor Proteins / Q000235:genetics; D014700:Verapamil / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D025581:Neurofibromin 2; D011799:Quinazolines; D025521:Tumor Suppressor Proteins; D013629:Tamoxifen; D015735:Mifepristone; D003606:Dacarbazine; D008687:Metformin; D014700:Verapamil; D000069347:Erlotinib Hydrochloride; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes; D019808:Losartan; D006918:Hydroxyurea; D000077204:Temozolomide