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      A comprehensive review in improving delivery of small-molecule chemotherapeutic agents overcoming the blood-brain/brain tumor barriers for glioblastoma treatment

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          Abstract

          Glioblastoma (GBM) is the most common and lethal primary brain tumor which is highly resistant to conventional radiotherapy and chemotherapy, and cannot be effectively controlled by surgical resection. Due to inevitable recurrence of GBM, it remains essentially incurable with a median overall survival of less than 18 months after diagnosis. A great challenge in current therapies lies in the abrogated delivery of most of the chemotherapeutic agents to the tumor location in the presence of blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB). These protective barriers serve as a selectively permeable hurdle reducing the efficacy of anti-tumor drugs in GBM therapy. This work systematically gives a comprehensive review on: (i) the characteristics of the BBB and the BBTB, (ii) the influence of BBB/BBTB on drug delivery and the screening strategy of small-molecule chemotherapeutic agents with promising BBB/BBTB-permeable potential, (iii) the strategies to overcome the BBB/BBTB as well as the techniques which can lead to transient BBB/BBTB opening or disruption allowing for improving BBB/BBTB-penetration of drugs. It is hoped that this review provide practical guidance for the future development of small BBB/BBTB-permeable agents against GBM as well as approaches enhancing drug delivery across the BBB/BBTB to GBM.

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          Current state of immunotherapy for glioblastoma

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            Central nervous system pericytes in health and disease.

            Pericytes are uniquely positioned within the neurovascular unit to serve as vital integrators, coordinators and effectors of many neurovascular functions, including angiogenesis, blood-brain barrier (BBB) formation and maintenance, vascular stability and angioarchitecture, regulation of capillary blood flow and clearance of toxic cellular byproducts necessary for proper CNS homeostasis and neuronal function. New studies have revealed that pericyte deficiency in the CNS leads to BBB breakdown and brain hypoperfusion resulting in secondary neurodegenerative changes. Here we review recent progress in understanding the biology of CNS pericytes and their role in health and disease.
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              Single-agent bevacizumab or lomustine versus a combination of bevacizumab plus lomustine in patients with recurrent glioblastoma (BELOB trial): a randomised controlled phase 2 trial.

              Treatment options for recurrent glioblastoma are scarce, with second-line chemotherapy showing only modest activity against the tumour. Despite the absence of well controlled trials, bevacizumab is widely used in the treatment of recurrent glioblastoma. Nonetheless, whether the high response rates reported after treatment with this drug translate into an overall survival benefit remains unclear. We report the results of the first randomised controlled phase 2 trial of bevacizumab in recurrent glioblastoma.
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                Author and article information

                Journal
                Drug Deliv
                Drug Deliv
                IDRD
                idrd20
                Drug Delivery
                Taylor & Francis
                1071-7544
                1521-0464
                2019
                16 May 2019
                : 26
                : 1
                : 551-565
                Affiliations
                [a ]State Key Laboratory of Medicinal Chemical Biology, Nankai University , Tianjin, China;
                [b ]Department of Chemistry, Yale University , New Haven, CT, USA
                Author notes

                Supplemental data for this article is available online at https://doi.org/10.1080/10717544.2019.1616235.

                CONTACT Liang Wang lwang@ 123456nankai.edu.cn ;
                Yue Chen yuechen@ 123456nankai.edu.cn State Key Laboratory of Medicinal Chemical Biology, Nankai Univeristy , Tianjin, China
                Article
                1616235
                10.1080/10717544.2019.1616235
                6534214
                31928355
                9f591273-f070-4fa3-9b95-2cbad1d81342
                © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 12 March 2019
                : 04 May 2019
                : 04 May 2019
                Page count
                Figures: 4, Tables: 1, Pages: 15, Words: 13818
                Funding
                Funded by: National Natural Science Foundation of China (NSFC) 10.13039/501100001809
                Funded by: National Science Fund for Distinguished Young Scholars
                This work was supported by the National Natural Science Foundation of China (NSFC) [Grant No. 81573282 to Y.C.; Grant No. 81703350 to L.W.]; the National Science Fund for Distinguished Young Scholars [Grant No. 81625021] to Y.C.; and the Fundamental Research Funds for the Central Universities and Hundred Young Academic Leaders Program of Nankai University.
                Categories
                Research Article

                Pharmacology & Pharmaceutical medicine
                small-molecule agents,drug delivery,blood-brain barrier,blood-brain tumor barrier,glioblastoma

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