TY  - JOUR
A1  - Novakova, Iveta
A1  - Subileau, Eva-Anne
A1  - Toegel, Stefan
A1  - Gruber, Daniela
A1  - Lachmann, Bodo
A1  - Urban, Ernst
A1  - Chesne, Christophe
A1  - Noe, Christian R.
A1  - Neuhaus, Winfried
T1  - Transport Rankings of Non-Steroidal Antiinflammatory Drugs across Blood-Brain Barrier In Vitro Models
JF  - PLoS ONE
N2  - The aim of this work was to conduct a comprehensive study about the transport properties of NSAIDs across the blood-brain barrier (BBB) in vitro. Transport studies with celecoxib, diclofenac, ibuprofen, meloxicam, piroxicam and tenoxicam were accomplished across Transwell models based on cell line PBMEC/C1-2, ECV304 or primary rat brain endothelial cells. Single as well as group substance studies were carried out. In group studies substance group compositions, transport medium and serum content were varied, transport inhibitors verapamil and probenecid were added. Resulted permeability coefficients were compared and normalized to internal standards diazepam and carboxyfluorescein. Transport rankings of NSAIDs across each model were obtained. Single substance studies showed similar rankings as corresponding group studies across PBMEC/C1-2 or ECV304 cell layers. Serum content, glioma conditioned medium and inhibitors probenecid and verapamil influenced resulted permeability significantly. Basic differences of transport properties of the investigated NSAIDs were similar comparing all three in vitro BBB models. Different substance combinations in the group studies and addition of probenecid and verapamil suggested that transporter proteins are involved in the transport of every tested NSAID. Results especially underlined the importance of same experimental conditions (transport medium, serum content, species origin, cell line) for proper data comparison.
KW  - NSAIDs
KW  - astrocytes
KW  - transport inhibition assay
KW  - drug-drug interactions
KW  - diazepam
KW  - permeability
KW  - glioma
KW  - scanning electron microscopy
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-119992
VL  - 9
IS  - 1
ER  - 
TY  - JOUR
A1  - Rieger, Johannes
A1  - Bähr, Oliver
A1  - Maurer, Gabriele D.
A1  - Hattingen, Elke
A1  - Franz, Kea
A1  - Brucker, Daniel
A1  - Walenta, Stefan
A1  - Kämmerer, Ulrike
A1  - Coy, Johannes F.
A1  - Weller, Michael
A1  - Steinbach, Joachim P.
T1  - ERGO: A pilot study of ketogenic diet in recurrent glioblastoma
JF  - International Journal of Oncology
N2  - Limiting dietary carbohydrates inhibits glioma growth in preclinical models. Therefore, the ERGO trial (NCT00575146) examined feasibility of a ketogenic diet in 20 patients with recurrent glioblastoma. Patients were put on a low-carbohydrate, ketogenic diet containing plant oils. Feasibility was the primary endpoint, secondary endpoints included the percentage of patients reaching urinary ketosis, progression-free survival (PFS) and overall survival. The effects of a ketogenic diet alone or in combination with bevacizumab was also explored in an orthotopic U87MG glioblastoma model in nude mice. Three patients (15%) discontinued the diet for poor tolerability. No serious adverse events attributed to the diet were observed. Urine ketosis was achieved at least once in 12 of 13 (92%) evaluable patients. One patient achieved a minor response and two patients had stable disease after 6 weeks. Median PFS of all patients was 5 (range, 3-13) weeks, median survival from enrollment was 32 weeks. The trial allowed to continue the diet beyond progression. Six of 7 (86%) patients treated with bevacizumab and diet experienced an objective response, and median PFS on bevacizumab was 20.1 (range, 12-124) weeks, for a PFS at 6 months of 43%. In the mouse glioma model, ketogenic diet alone had no effect on median survival, but increased that of bevacizumab-treated mice from 52 to 58 days (p<0.05). In conclusion, a ketogenic diet is feasible and safe but probably has no significant clinical activity when used as single agent in recurrent glioma. Further clinical trials are necessary to clarify whether calorie restriction or the combination with other therapeutic modalities, such as radiotherapy or anti-angiogenic treatments, could enhance the efficacy of the ketogenic diet.
KW  - feasibility
KW  - glucose
KW  - glioma
KW  - metabolism
KW  - ketogenic diet
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-121170
VL  - 44
IS  - 6
ER  -