0000000000677350
AUTHOR
Roland Goldbrunner
Reprogramming of Pericyte-Derived Cells of the Adult Human Brain into Induced Neuronal Cells
SummaryReprogramming of somatic cells into neurons provides a new approach toward cell-based therapy of neurodegenerative diseases. A major challenge for the translation of neuronal reprogramming into therapy is whether the adult human brain contains cell populations amenable to direct somatic cell conversion. Here we show that cells from the adult human cerebral cortex expressing pericyte hallmarks can be reprogrammed into neuronal cells by retrovirus-mediated coexpression of the transcription factors Sox2 and Mash1. These induced neuronal cells acquire the ability of repetitive action potential firing and serve as synaptic targets for other neurons, indicating their capability of integrat…
BIOM-08. DNA METHYLATION-BASED SUBGROUPING PREDICTS SURVIVAL BENEFIT FROM LOMUSTINE/TEMOZOLOMID COMBINATION THERAPY IN MGMT PROMOTOR-METHYLATED GLIOBLASTOMA
Abstract BACKGROUND The CeTeG/NOA-09 trial showed that lomustine/temozolomide chemotherapy prolongs survival for newly diagnosed MGMT-methylated glioblastoma patients. Previous reports on temozolomide monotherapy suggested, that the survival benefit of temozolomide in MGMT-methylated tumors may be restricted to the RTK II methylation subgroup and absent in RTK I and MES subgroups. To identify patients with a particularly strong benefit from CCNU/TMZ, we explored the association of methylation subgroups with outcome after lomustine/temozolomide therapy. METHODS All patients from the CeTeG/NOA-09 trial with sufficiently available tumor tissue (n = 98) underwent 850K methylation array analysis…
ACTR-58. PHASE III TRIAL OF CCNU/TEMOZOLOMIDE (TMZ) COMBINATION THERAPY VS. STANDARD TMZ THERAPY FOR NEWLY DIAGNOSED MGMT-METHYLATED GLIOBLASTOMA PATIENTS: THE CeTeg/NOA-09 trial
There is an urgent need for more effective therapies in glioblastoma (GBM). Data from the single arm UKT-03 trial (Glas et al., J Clin Oncol 27, 1257, 2009) suggested that combined lomustine/temozolomide (CCNU/TMZ) therapy might have superior activity in MGMT-methylated GBM. The phase III CeTeG/NOA-09 trial was set up to test this hypothesis in a randomized setting. Patients with MGMT-methylated GBM were randomized (1:1) for standard therapy with daily TMZ (75 mg/m2) during local radiotherapy (RT, 30 x 2 Gy) followed by 6 courses of TMZ (150–200 mg/m2/day for 5 days q4w) or experimental therapy with CCNU/TMZ in addition to local RT. Six 6-week courses of CCNU/TMZ (CCNU 100 mg/m2 d1, TMZ 100…
Lomustine-temozolomide combination therapy versus standard temozolomide therapy in patients with newly diagnosed glioblastoma with methylated MGMT promoter (CeTeG/NOA–09): a randomised, open-label, phase 3 trial
Summary Background There is an urgent need for more effective therapies for glioblastoma. Data from a previous unrandomised phase 2 trial suggested that lomustine-temozolomide plus radiotherapy might be superior to temozolomide chemoradiotherapy in newly diagnosed glioblastoma with methylation of the MGMT promoter. In the CeTeG/NOA-09 trial, we aimed to further investigate the effect of lomustine-temozolomide therapy in the setting of a randomised phase 3 trial. Methods In this open-label, randomised, phase 3 trial, we enrolled patients from 17 German university hospitals who were aged 18–70 years, with newly diagnosed glioblastoma with methylated MGMT promoter, and a Karnofsky Performance …