scholarly journals Histone Deacetylase Inhibitors as Therapeutic Agents for Acute Central Nervous System Injuries

2011 ◽  
Vol 17 (5-6) ◽  
pp. 448-456 ◽  
Author(s):  
Na’ama A Shein ◽  
Esther Shohami
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors ◽  
Therapeutic Agents

scholarly journals Histone deacetylase inhibition enhances the therapeutic effects of methotrexate on primary central nervous system lymphoma

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Kenji Fujimoto ◽  
Naoki Shinojima ◽  
Mitsuhiro Hayashi ◽  
Tomoyuki Nakano ◽  
Koichi Ichimura ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cell Viability ◽  
Tumor Cells ◽  
Histone Deacetylase ◽  
Protein Modification ◽  
Histone Deacetylase Inhibitors ◽  
Central Nervous System Lymphoma ◽  
Therapeutic Effects ◽  
Combined Effects

Abstract Background Polyglutamylation is a reversible protein modification that commonly occurs in tumor cells. Methotrexate (MTX) in tumor cells is polyglutamylated and strongly binds to dihydrofolate reductase (DHFR) without competitive inhibition by leucovorin. Therefore, tumor cells with high polyglutamylation levels are supposed to be selectively killed, whereas normal cells with lower polyglutamylation are rescued by leucovorin. This study investigated the combined effects of MTX plus histone deacetylase inhibitors (HDACIs), which upregulate MTX polyglutamylation, in primary central nervous system lymphoma (PCNSL). Methods We evaluated cell viability after MTX treatment and leucovorin rescue and compared the expression of folylpolyglutamate synthetase (FPGS), γ-glutamyl hydrolase (GGH), and DHFR in 2 human PCNSL-derived cell lines (HKBML and TK) and a human Burkitt lymphoma cell line (TL-1). Combination treatments were created using 4 HDACIs: panobinostat, vorinostat, sodium butyrate, and valproic acid. The expression of DHFR was examined as well as ratios of FPGS/GGH expression. The combined effects of MTX plus HDACIs were evaluated using a cell viability assay, mass spectroscopy imaging, and subcutaneous and intracranial xenograft models. Results HDACIs upregulated the ratio of FPGS/GGH expression resulting in increased polyglutamylation of MTX, but also downregulated expression of the target molecule of MTX: DHFR. The combination of MTX and vorinostat decreased cell viability in vitro (P < .05) and tumor volumes in a subcutaneous model (P < .0001), and prolonged survival in an intracranial model (P < .01), relative to controls. Conclusion HDACIs enhanced the therapeutic effect of MTX through increased polyglutamylation of MTX and concomitant downregulation of DHFR expression.

scholarly journals The Past, Present and Future of Flow Cytometry in Central Nervous System Malignancies

2021 ◽  
Vol 4 (1) ◽  
pp. 11
Author(s):  
Evrysthenis Vartholomatos ◽  
George Vartholomatos ◽  
George A. Alexiou ◽  
Georgios S. Markopoulos
Keyword(s):  
Central Nervous System ◽  
Flow Cytometry ◽  
Nervous System ◽  
Therapeutic Agents ◽  
Phenotypic Characterization ◽  
Cell Phenotype ◽  
Analytical Technique ◽  
The Past ◽  
Current Review

Central nervous system malignancies (CNSMs) are categorized among the most aggressive and deadly types of cancer. The low median survival in patients with CNSMs is partly explained by the objective difficulties of brain surgeries as well as by the acquired chemoresistance of CNSM cells. Flow Cytometry is an analytical technique with the ability to quantify cell phenotype and to categorize cell populations on the basis of their characteristics. In the current review, we summarize the Flow Cytometry methodologies that have been used to study different phenotypic aspects of CNSMs. These include DNA content analysis for the determination of malignancy status and phenotypic characterization, as well as the methodologies used during the development of novel therapeutic agents. We conclude with the historical and current utility of Flow Cytometry in the field, and we propose how we can exploit current and possible future methodologies in the battle against this dreadful type of malignancy.

scholarly journals Delivery of Therapeutic Agents to the Central Nervous System and the Promise of Extracellular Vesicles

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 492
Author(s):  
Charlotte A. René ◽  
Robin J. Parks
Keyword(s):  
Central Nervous System ◽  
Endothelial Cells ◽  
Nervous System ◽  
Blood Brain Barrier ◽  
Extracellular Vesicles ◽  
Therapeutic Agents ◽  
Target Cells ◽  
Significant Barrier ◽  
The Central Nervous System ◽  
Delivery Vehicles

The central nervous system (CNS) is surrounded by the blood–brain barrier (BBB), a semipermeable border of endothelial cells that prevents pathogens, solutes and most molecules from non-selectively crossing into the CNS. Thus, the BBB acts to protect the CNS from potentially deleterious insults. Unfortunately, the BBB also frequently presents a significant barrier to therapies, impeding passage of drugs and biologicals to target cells within the CNS. This review provides an overview of different approaches to deliver therapeutics across the BBB, with an emphasis in extracellular vesicles as delivery vehicles to the CNS.

Histone Deacetylase Inhibitors: Emerging Anticancer Therapeutic Agents?

2005 ◽  
Vol 7 ◽  
pp. S19-S30 ◽  
Author(s):  
Rebecca Kristeleit ◽  
Peter Fong ◽  
G. Wynne Aherne ◽  
Johann de Bono
Keyword(s):  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors ◽  
Therapeutic Agents

scholarly journals The neuroprotection effects of exosome in central nervous system injuries: A new target for therapeutic intervention

2021 ◽  
Author(s):  
Li Zhang ◽  
Lei Mao ◽  
Handong Wang
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neurological Disorders ◽  
Therapeutic Agents ◽  
Great Promise ◽  
Nuclear Factor ◽  
Cns Injury ◽  
Cord Injury ◽  
Extracellular Regulated Protein Kinases ◽  
Light Chain Enhancer

Abstract Central nervous system (CNS) injuries, including traumatic brain injury (TBI), spinal cord injury (SCI) and subarachnoid hemorrhage (SAH), are the most common cause of death and disability around the world. As a key subset of extracellular vesicles (EVs), exosomes have recently attracted great attentions due to their functions in remodeling extracellular matrix, and transmitting signals and molecules. A large number of studies have suggested that exosomes played an important role in brain development and involved in many neurological disorders, particularly in CNS injuries. It has been proposed that exosomes could improve cognition function, inhibit apoptosis, suppress inflammation, regulate autophagy and protect blood brain barrier (BBB) in CNS injuries via different molecules and pathways including microRNA (miRNA), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), ph1osphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B (PI3K/AKT), Notch1 and extracellular regulated protein kinases (ERK). Therefore, exosomes showed great promise as potential targets in CNS injuries. In this article, we present a review highlighting the applications of exosomes in CNS injuries. Hence, on the basis of these properties and effects, exosomes may be developed as therapeutic agents for CNS injury patients.

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