{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["13(9)"],"submitter":["Oehler C"],"pubmed_abstract":["Concurrent radiochemotherapy for medulloblastoma includes the microtubule disrupting agent vincristine; however, vincristine alone or as part of a combined treatment regimen is highly toxic. A major goal is therefore to replace vincristine with novel potent chemotherapeutic agents-in particular, with microtubule stabilizing and destabilizing compounds-with a larger therapeutic window. Here, we investigated the antiproliferative, cytotoxic and radiosensitizing effect of patupilone (epothilone B [EPO906]), a novel, non-taxane-related and nonneurotoxic microtubule-stabilizing agent in human medulloblastoma cell lines. The antiproliferative and cytotoxic effects of patupilone alone and in combination with ionizing radiation was determined in the 3 representative human medulloblastoma cell lines D341Med, D425Med, and DAOY. Patupilone alone effectively reduced the proliferative activity and clonogenicity of all medulloblastoma cell lines tested at picomolar concentrations (50-200 pM) and resulted in an at least additive anticlonogenic effect in combination with clinically relevant doses of ionizing radiation (2 or 5 Gy). Cell-cycle analysis revealed a sequential G2-M arrest and sub-G1 accumulation in a dose- and treatment-dependent manner after exposure to patupilone. In tumor xenografts derived from D425Med cells, a minimal treatment regimen with patupilone and fractionated irradiation (1 × 2 mg/kg plus 3 × 3 Gy) resulted in an extended tumor growth delay for the 2 single treatment modalities alone and a supra-additive treatment response for the combined treatment modality, with complete tumor regressions. These results demonstrate the potent efficacy of patupilone against medulloblastoma cell lines and indicate that patupilone represents a promising candidate to replace vincristine as part of a combined treatment strategy with ionizing radiation."],"journal":["Neuro-oncology"],"pagination":["1000-10"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3158010"],"repository":["biostudies-literature"],"pubmed_title":["The microtubule stabilizer patupilone (epothilone B) is a potent radiosensitizer in medulloblastoma cells."],"pmcid":["PMC3158010"],"pubmed_authors":["Broggini-Tenzer A","Oehler C","Frei K","Grotzer MA","Pruschy M","Furmanova P","von Bueren AO","Orlowski K","Rutkowski S"],"additional_accession":[]},"is_claimable":false,"name":"The microtubule stabilizer patupilone (epothilone B) is a potent radiosensitizer in medulloblastoma cells.","description":"Concurrent radiochemotherapy for medulloblastoma includes the microtubule disrupting agent vincristine; however, vincristine alone or as part of a combined treatment regimen is highly toxic. A major goal is therefore to replace vincristine with novel potent chemotherapeutic agents-in particular, with microtubule stabilizing and destabilizing compounds-with a larger therapeutic window. Here, we investigated the antiproliferative, cytotoxic and radiosensitizing effect of patupilone (epothilone B [EPO906]), a novel, non-taxane-related and nonneurotoxic microtubule-stabilizing agent in human medulloblastoma cell lines. The antiproliferative and cytotoxic effects of patupilone alone and in combination with ionizing radiation was determined in the 3 representative human medulloblastoma cell lines D341Med, D425Med, and DAOY. Patupilone alone effectively reduced the proliferative activity and clonogenicity of all medulloblastoma cell lines tested at picomolar concentrations (50-200 pM) and resulted in an at least additive anticlonogenic effect in combination with clinically relevant doses of ionizing radiation (2 or 5 Gy). Cell-cycle analysis revealed a sequential G2-M arrest and sub-G1 accumulation in a dose- and treatment-dependent manner after exposure to patupilone. In tumor xenografts derived from D425Med cells, a minimal treatment regimen with patupilone and fractionated irradiation (1 × 2 mg/kg plus 3 × 3 Gy) resulted in an extended tumor growth delay for the 2 single treatment modalities alone and a supra-additive treatment response for the combined treatment modality, with complete tumor regressions. These results demonstrate the potent efficacy of patupilone against medulloblastoma cell lines and indicate that patupilone represents a promising candidate to replace vincristine as part of a combined treatment strategy with ionizing radiation.","dates":{"release":"2011-01-01T00:00:00Z","publication":"2011 Sep","modification":"2024-11-11T20:41:56.225Z","creation":"2019-03-27T00:43:07Z"},"accession":"S-EPMC3158010","cross_references":{"pubmed":["21743064"],"doi":["10.1093/neuonc/nor069"]}}