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This case report shows that real-time MRI may aid in the precision of intra-arterial delivery of bevacizumab to butterfly glioblastoma. Fast clinical improvement, decrease of contrast enhancing status, and no serious adverse effects were observed at discharge from hospital. The patient regained pre-recurrent neurological status for 2 months with a subsequent fast clinical decline and an increase in tumor volume. The patient underwent a second procedure of intra-arterial delivery of bevacizumab to the brain, with substantial clinical and radiological improvement, but not the level of improvement observed after the first procedure. Another clinical decline occurred with an increase in tumor size and the patient was treated 2 months later with a third intra-arterial infusion of bevacizumab. While another positive effect was achieved, it was less pronounced than before, and the patient died 1.5 months later. There were no technical, ischemic or other complications during the procedures. The patient survived 218 days from the first symptoms of tumor recurrence, 190 days from the first MRI, and 175 days from the first intra-arterial treatment of bevacizumab., Competing Interests: Competing interests: PW and MJ are co-owners of IntraART, LLC and Ti-com, LLC, but they are not directly related to this case report., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Patients suffering from malignant brain tumors are burdened with a grim prognosis. The blood brain barrier is considered a primary obstacle in therapeutic drug delivery to the brain. Intra-arterial (IA) delivery of therapeutic agents following osmotic BBB opening has been attempted for years, but high variability has limited its widespread implementation. It has been recently shown in animal studies that MRI is superior to X-ray for guiding IA infusions, as it allows direct visualization of the brain parenchyma perfused and facilitates predictable drug targeting. Moreover, PET imaging has revealed that IA, not intravenous, delivery of bevacizumab results in brain accumulation, providing strong rationale for utilizing the IA route. Here, we present our experience in a patient with recurrent butterfly glioblastoma enrolled in first-in-man MRI-guided neurointervention for targeted IA drug delivery., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Patients with malignant brain tumors have a poor prognosis. The blood-brain barrier (BBB) is considered a primary obstacle in therapeutic drug delivery to the brain. Intra-arterial (IA) delivery of therapeutic agents following osmotic BBB opening has been attempted for years, but high variability has limited its widespread implementation. It has recently been shown in animal studies that MRI is superior to X-ray for guiding IA infusions, as it allows direct visualization of the brain parenchyma supplied by the catheter and facilitates predictable drug targeting. Moreover, PET imaging has shown that IA rather than intravenous delivery of bevacizumab results in accumulation in the brain, providing a strong rationale for using the IA route. We present a patient with recurrent butterfly glioblastoma enrolled in a first-in-man MRI-guided neurointervention for targeted IA drug delivery., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Glioblastoma (GBM) is an aggressive malignancy associated with profound host immunosuppression. Microglia and macrophages infiltrating GBM acquire the pro-tumorigenic, M2 phenotype and support tumor invasion, proliferation, survival, angiogenesis and block immune responses both locally and systematically. Mechanisms responsible for immunological deficits in GBM patients are poorly understood. We analyzed immune/inflammatory gene expression in five datasets of low and high grade gliomas, and performed Gene Ontology and signaling pathway analyses to identify defective transcriptional responses. The expression of many immune/inflammatory response and TLR signaling pathway genes was reduced in high grade gliomas compared to low grade gliomas. In particular, we found the reduced expression of the IKBKB, a gene coding for IKKβ, which phosphorylates IκB proteins and represents a convergence point for most signal transduction pathways leading to NFκB activation. The reduced IKBKB expression and IKKβ levels in GBM tissues were demonstrated by qPCR, Western blotting and immunohistochemistry. The IKKβ expression was down-regulated in microglia/macrophages infiltrating glioblastoma. NFκB activation, prominent in microglia/macrophages infiltrating low grade gliomas, was reduced in microglia/macrophages in glioblastoma tissues. Down-regulation of IKBKB expression and NFκB signaling in microglia/macrophages infiltrating glioblastoma correlates with defective expression of immune/inflammatory genes and M2 polarization that may result in the global impairment of anti-tumor immune responses in glioblastoma.