TY  - JOUR
A1  - Feldheim, Jonas
A1  - Wend, David
A1  - Lauer, Mara J.
A1  - Monoranu, Camelia M.
A1  - Glas, Martin
A1  - Kleinschnitz, Christoph
A1  - Ernestus, Ralf-Ingo
A1  - Braunger, Barbara M.
A1  - Meybohm, Patrick
A1  - Hagemann, Carsten
A1  - Burek, Malgorzata
T1  - Protocadherin Gamma C3 (PCDHGC3) is strongly expressed in glioblastoma and its high expression is associated with longer progression-free survival of patients
JF  - International Journal of Molecular Sciences
N2  - Protocadherins (PCDHs) belong to the cadherin superfamily and represent the largest subgroup of calcium-dependent adhesion molecules. In the genome, most PCDHs are arranged in three clusters, α, β, and γ on chromosome 5q31. PCDHs are highly expressed in the central nervous system (CNS). Several PCDHs have tumor suppressor functions, but their individual role in primary brain tumors has not yet been elucidated. Here, we examined the mRNA expression of PCDHGC3, a member of the PCDHγ cluster, in non-cancerous brain tissue and in gliomas of different World Health Organization (WHO) grades and correlated it with the clinical data of the patients. We generated a PCDHGC3 knockout U343 cell line and examined its growth rate and migration in a wound healing assay. We showed that PCDHGC3 mRNA and protein were significantly overexpressed in glioma tissue compared to a non-cancerous brain specimen. This could be confirmed in glioma cell lines. High PCDHGC3 mRNA expression correlated with longer progression-free survival (PFS) in glioma patients. PCDHGC3 knockout in U343 resulted in a slower growth rate but a significantly faster migration rate in the wound healing assay and decreased the expression of several genes involved in WNT signaling. PCDHGC3 expression should therefore be further investigated as a PFS-marker in gliomas. However, more studies are needed to elucidate the molecular mechanisms underlying the PCDHGC3 effects.
KW  - glioblastoma multiforme
KW  - glioma
KW  - astrocytoma
KW  - recurrence
KW  - relapse
KW  - mRNA
KW  - protein
KW  - brain
KW  - expression
KW  - PCDHGC3
KW  - WNT signaling
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284433
SN  - 1422-0067
VL  - 23
IS  - 15
ER  - 
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  -