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Delivery of bevacizumab by intracranial injection: assessment in glioma model

Authors Liu YX, Liu WJ, Zhang HR, Zhang ZW

Received 14 December 2017

Accepted for publication 20 March 2018

Published 8 May 2018 Volume 2018:11 Pages 2673—2683

DOI https://doi.org/10.2147/OTT.S159913

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 3

Editor who approved publication: Dr Ingrid Espinoza


Yu-Xiao Liu,1,* Wen-Jia Liu,2,* Hui-Ru Zhang,1,3 Zhi-Wen Zhang1

1Department of Neurosurgery, First Affiliated Hospital of Chinese PLA General Hospital, Beijing, People’s Republic of China; 2Beijing Institute of Biotechnology, Beijing, People’s Republic of China; 3College of Biological Engineering, HeNan University of Technology, Beijing, People’s Republic of China

*These authors contributed equally to this work

Background:
Many reports have indicated that the intravenous administration of bevacizumab produces a number of systemic side effects. Therefore, we investigated the therapeutic effects of intratumoral bevacizumab administration using a glioma animal model.
Methods: The glioma cell lines U251 and U87 that carried luciferase were implanted into the brains of mice to develop glioma models. Glioma-bearing mice were treated with bevacizumab intravenously or intratumorally by Alzet micro-osmotic pumps, and the survival time of mice was monitored. Tumor volumes and location were observed by fluorescence imaging and histological analysis. Levels of microvessel marker, cancer stem cell marker as well as angiogenesis-, invasion-, and inflammation-related factors in tumors were examined by immunohistochemical staining.
Results: Mice treated with intratumoral low-dose bevacizumab had smaller tumor volumes, longer survival time, lower microvessel density, and fewer cancer stem cells as compared with untreated and intravenously treated mice. Furthermore, expression levels of inflammation-related factors increased signifiwhereas that of angiogenesis- and invasion-related factors decreased in intratumorally treated animals, compared with intravenously treated mice.
Conclusion: These results implied bevacizumab delivery by intratumoral injection via Alzet micro-osmotic pumps may be a more effective and safer protocol for treating gliomas.

Keywords:
bevacizumab, anti-angiogenic, glioma cell line, intratumoral delivery, fluorescence imaging

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