PURPOSE: 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.
PURPOSE: 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: Ileana C Cuevas; Alison L Slocum; Peter Jun; Joseph F Costello; Andrew W Bollen; Gregory J Riggins; Michael W McDermott; Anita Lal Journal: Cancer Res Date: 2005-06-15 Impact factor: 12.701
Authors: Corinna Seliger; Christoph R Meier; Claudia Becker; Susan S Jick; Martin Proescholdt; Ulrich Bogdahn; Peter Hau; Michael F Leitzmann Journal: PLoS One Date: 2017-07-14 Impact factor: 3.240
Authors: Erika Guimarães; Rodrigo Machado; Matheus de Castro Fonseca; Andressa França; Clarissa Carvalho; Ana Cândida Araújo E Silva; Brígida Almeida; Puebla Cassini; Bárbara Hissa; Luciana Drumond; Carlos Gonçalves; Gabriel Fernandes; Marina De Brot; Márcio Moraes; Lucíola Barcelos; José Miguel Ortega; André Oliveira; M Fátima Leite Journal: PLoS One Date: 2017-04-04 Impact factor: 3.240