ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2015
Combined local blood-brain barrier opening and systemic methotrexate for the treatment of brain tumors.
Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Breaking the Barrier of Brain Disease Therapeutics: Advocating Targeted Drug Delivery for Improved Neuro-Resident Interventions.AAPS PharmSciTech · 2026Review
- Nanoparticle-Based Approaches for Glioblastoma Treatment: Advances and Future Prospects.CNS & neurological disorders drug targets · 2026Review
- Nose-to-Brain (N2B) Delivery: An Alternative Route for the Delivery of Biologics in the Management and Treatment of Central Nervous System Disorders.Pharmaceutics · 2023Review
- Albumin-Methotrexate Prodrug Analogues That Undergo Intracellular Reactivation Following Entrance into Cancerous Glioma Cells.Pharmaceutics · 2021Article
- Nanomaterial-based blood-brain-barrier (BBB) crossing strategies.Biomaterials · 2019Review
- A Novel Compound Targeting Protease Receptor 1 Activators for the Treatment of Glioblastoma.Frontiers in neurology · 2018Article
- Advances in drug delivery to high grade gliomas.Brain pathology (Zurich, Switzerland) · 2016Review
- Convection-enhanced Drug Delivery for Glioblastoma: A Systematic Review Focused on Methodological Differences in the Use of the Convection-enhanced Delivery Method.Asian journal of neurosurgeryReview
Corrections and comments
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Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite aggressive therapy, existing treatments offer poor prognosis for glioblastoma multiforme patients, in part due to poor penetration of most drugs across the blood-brain barrier (BBB). We propose a minimal-invasive combined treatment approach consisting of local BBB disruption in the tumor in parallel to systemic drug administration. Local BBB disruption is obtained by convection-enhanced delivery of a novel BBB disruption agent, enabling efficient/targeted delivery of the systemically administered drug by the tumors own vasculature. Various human serum albumin (HSA) analogs were synthesized and screened for BBB disruption efficacy in custom in vitro systems. The candidate analogs were then delivered into naïve rat brains by convection-enhanced delivery and screened for maximal BBB disruption and minimal brain toxicity. These studies found a noncationized/neutralized analog, ethylamine (EA)-HSA, to be the optimal BBB-opening agent. Immunocytochemical studies suggested that BBB disruption by EA-HSA may be explained by alterations in occludin expression. Finally, an efficacy study in rats bearing intracranial gliomas was performed. The rats were treated by convection-enhanced delivery of EA-HSA in parallel to systemic administration of Methotrexate, showing significant antineoplastic effects of the combined approached reflected in suppressed tumor growth and significantly (~x3) prolonged survival.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.