TY  - JOUR
A1  - Côté, Jérôme
A1  - Bovenzi, Veronica
A1  - Savard, Martin
A1  - Dubuc, Céléna
A1  - Fortier, Audrey
A1  - Neugebauer, Witold
A1  - Tremblay, Luc
A1  - Müller-Esterl, Werner
A1  - Tsanaclis, Ana-Maria
A1  - Lepage, Martin
A1  - Fortin, David
A1  - Gobeil, Fernand
T1  - Induction of selective blood-tumor barrier permeability and macromolecular transport by a biostable kinin b1 receptor agonist in a glioma rat model
T2  - PLoS One
N2  - Treatment of malignant glioma with chemotherapy is limited mostly because of delivery impediment related to the blood-brain tumor barrier (BTB). B1 receptors (B1R), inducible prototypical G-protein coupled receptors (GPCR) can regulate permeability of vessels including possibly that of brain tumors. Here, we determine the extent of BTB permeability induced by the natural and synthetic peptide B1R agonists, LysdesArg9BK (LDBK) and SarLys[DPhe8]desArg9BK (NG29), in syngeneic F98 glioma-implanted Fischer rats. Ten days after tumor inoculation, we detected the presence of B1R on tumor cells and associated vasculature. NG29 infusion increased brain distribution volume and uptake profiles of paramagnetic probes (Magnevist and Gadomer) at tumoral sites (T1-weighted imaging). These effects were blocked by B1R antagonist and non-selective cyclooxygenase inhibitors, but not by B2R antagonist and non-selective nitric oxide synthase inhibitors. Consistent with MRI data, systemic co-administration of NG29 improved brain tumor delivery of Carboplatin chemotherapy (ICP-Mass spectrometry). We also detected elevated B1R expression in clinical samples of high-grade glioma. Our results documented a novel GPCR-signaling mechanism for promoting transient BTB disruption, involving activation of B1R and ensuing production of COX metabolites. They also underlined the potential value of synthetic biostable B1R agonists as selective BTB modulators for local delivery of different sized-therapeutics at (peri)tumoral sites.
Y1  - 2012
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/22820
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-228201
SN  - 1932-6203
VL  - 7
IS  - (5): e37485
PB  - PLoS
CY  - Lawrence, Kan.
ER  -