@article{1c542b4f68704312a7f6c12041d2948b,
title = "Therapeutic effect of cabazitaxel and blood-brain barrier opening in a patient-derived glioblastoma model",
abstract = "Treatment of glioblastoma and other diseases in the brain is especially challenging due to the blood-brain barrier, which effectively protects the brain parenchyma. In this study we show for the first time that cabazitaxel, a semi-synthetic derivative of docetaxel can cross the blood-brain barrier and give a significant therapeutic effect in a patient-derived orthotopic model of glioblastoma. We show that the drug crosses the blood-brain barrier more effectively in the tumor than in the healthy brain due to reduced expression of p-glycoprotein efflux pumps in the vasculature of the tumor. Surprisingly, neither ultrasound-mediated blood-brain barrier opening (sonopermeation) nor drug formulation in polymeric nanoparticles could increase either accumulation of the drug in the brain or therapeutic effect. This indicates that for hydrophobic drugs, sonopermeation of the blood brain barrier might not be sufficient to achieve improved drug delivery. Nonetheless, our study shows that cabazitaxel is a promising drug for the treatment of brain tumors.",
keywords = "Cabazitaxel, Glioblastoma, Orthotopic model, Sonopermeation",
author = "Einar Sulheim and Yrr M{\o}rch and Sofie Snipstad and Borgos, {Sven Even} and Hrvoje Miletic and Rolf Bjerkvig and {de Lange Davies}, Catharina and {\AA}slund, {Andreas K.O.}",
note = "Funding Information: Federica de Lorenzi at ExMi RWTH Aachen is thanked for help in histology analysis and training of the InForm segmentation system, Ida Sofie Jorstad and Ida Marie H{\o}iaas for SEM imaging. SEM imaging was performed at the NTNU Nanolab and The Research Council of Norway is acknowledged for the support to the Norwegian Micro-and Nano-Fabrication Facility, NorFab, project number 245963/F50. Formulation/synthesis of NP, NPMB and cab, as well as tissue extraction and LC-MS/MS quantification of cab was performed at SINTEF, and Anne Rein Hatletveit and Catherine L{\o}vmo are especially thanked for technical help. HES staining was performed by Ingunn Nervik at CMIC NTNU, MRI at the MR core facility NTNU, tumor implantation and animal housing at CoMed NTNU. The project was supported by The Central Norway Regional Health Authority, project number 46084000 and The Research Council of Norway project number 240316. Publisher Copyright: {\textcopyright} Ivyspring International Publisher.",
year = "2019",
doi = "10.7150/ntno.31479",
language = "English",
volume = "3",
pages = "103--112",
journal = "Nanotheranostics",
issn = "2206-7418",
publisher = "Ivyspring International Publishers",
number = "1",
}