Brian J Golbourn
Prominent publications by Brian J Golbourn
Brainstem blood brain barrier disruption using focused ultrasound: A demonstration of feasibility and enhanced doxorubicin delivery
[ PUBLICATION ]
Magnetic Resonance Image-guided Focused Ultrasound (MRgFUS) has been used to achieve transient blood brain barrier (BBB) opening without tissue injury. Delivery of a targeted ultrasonic wave causes an interaction between administered microbubbles and the capillary bed resulting in enhanced vessel permeability. The use of MRgFUS in the brainstem has not previously been shown but could provide value in the treatment of tumours such as Diffuse Intrinsic Pontine Glioma (DIPG) where the ...
|Known for Brain Barrier | Focused Ultrasound | Bbb Opening | Drug Delivery | Administered Microbubbles|
Malignant astrocytomas are highly invasive brain tumors. The Rho family of cytoskeletal GTPases are key regulators of astrocytoma migration and invasion; expression of the guanine nucleotide exchange factor ECT2 is elevated in primary astrocytomas and predicts both survival and malignancy. Mice bearing orthotopically implanted astrocytoma cells with diminished ECT2 levels following ECT2 knockdown exhibit longer survival. Although ECT2 is normally expressed in the nucleus, we show that ...
|Known for Astrocytoma Cells | Ect2 Expression | Amoeboid Phenotype | Binding Protein | Cdc42 Gtp|
Transcriptional profiling of GBM invasion genes identifies effective inhibitors of the LIM kinase-Cofilin pathway
[ PUBLICATION ]
Malignant gliomas are highly proliferative and invasive neoplasms where total surgical resection is often impossible and effective local radiation therapy difficult. Consequently, there is a need to develop a greater understanding of the molecular events driving invasion and to identify novel treatment targets. Using microarray analysis comparing normal brain samples and mesenchymal glioblastoma multiforme (GBM), we identified over 140 significant genes involved in cell migration and ...
|Known for Gbm Invasion | Lim Kinase | Cell Migration | Actin Filaments | Malignant Gliomas|
Proliferating cancer cells are characterized by high rates of glycolysis, lactate production, and altered mitochondrial metabolism. This metabolic reprogramming provides important metabolites for proliferation of tumor cells, including glioblastoma. These biological processes, however, generate oxidative stress that must be balanced through detoxification of reactive oxygen species (ROS). Using an unbiased retroviral loss-of-function screen in nontransformed human astrocytes, we ...
|Known for Oxidative Stress | Tumor Cells | Glioblastoma Growth | Pink1 Loss | Metabolic Reprogramming|
Inhibition of Aurora kinase B has been evaluated as a therapy to block solid tumor growth in breast cancer, hepatocellular carcinoma, lung adenocarcinoma, and colorectal cancer models. Aurora kinase inhibitors are in early clinical trials for the treatment of leukemia. We hypothesized that Aurora B inhibition would reduce malignant glioma cell viability and result in impaired tumor growth in vivo. Aurora B expression is greater in cultured malignant glioma U251 cells compared to ...
|Known for Aurora Kinase | Glioma Cell | Tumor Growth | Azd1152 Hqpa | Serine Threonine|
Mechanism of action and therapeutic efficacy of Aurora kinase B inhibition in MYC overexpressing medulloblastoma
[ PUBLICATION ]
Medulloblastoma comprises four molecular subgroups of which Group 3 medulloblastoma is characterized by MYC amplification and MYC overexpression. Lymphoma cells expressing high levels of MYC are susceptible to apoptosis following treatment with inhibitors of mitosis. One of the key regulatory kinases involved in multiple stages of mitosis is Aurora kinase B. We hypothesized that medulloblastoma cells that overexpress MYC would be uniquely sensitized to the apoptotic effects of Aurora B ...
|Known for Aurora Kinase | Neoplastic Humans | Myc Overexpressing | Cell Tumor | Molecular Subgroups|
Poly-ADP-Ribose Polymerase as a Therapeutic Target in Pediatric Diffuse Intrinsic Pontine Glioma and Pediatric High-Grade Astrocytoma
[ PUBLICATION ]
Pediatric high-grade astrocytomas (pHGA) and diffuse intrinsic pontine gliomas (DIPG) are devastating malignancies for which no effective therapies exist. We investigated the therapeutic potential of PARP1 inhibition in preclinical models of pHGA and DIPG. PARP1 levels were characterized in pHGA and DIPG patient samples and tumor-derived cell lines. The effects of PARP inhibitors veliparib, olaparib, and niraparib as monotherapy or as radiosensitizers on cell viability, DNA damage, and ...
|Known for Ribose Polymerase | Intrinsic Pontine | Parp1 Activity | Pediatric Diffuse | Cell Lines|
Medulloblastoma is the most common malignant pediatric brain tumor, with metastases present at diagnosis conferring a poor prognosis. Mechanisms of dissemination are poorly understood and metastatic lesions are genetically divergent from the matched primary tumor. Effective and less toxic therapies that target both compartments have yet to be identified. Here, we report that the analysis of several large nonoverlapping cohorts of patients with medulloblastoma reveals MET kinase as a ...
|Known for Sonic Hedgehog | Signal Transduction | Shh Medulloblastoma | Tumor Cell | Mice Mice|
First-line cancer therapies such as alkylating agents and radiation have limited survival benefits for Glioblastoma (GBM) patients. Current research strongly supports the notion that inhibition of aberrant tumor metabolism holds promise as a therapeutic strategy when used in combination with radiation and chemotherapy. Hexokinase 2 (HK2) has been shown to be a key driver of altered metabolism in GBM, and presents an attractive therapeutic target. To date, no study has fully assessed the ...
|Known for Hexokinase 2 | Tumor Metabolism | Glioblastoma Gbm | Cell Lines | Dna Damage|
ATM Regulates 3-Methylpurine-DNA Glycosylase and Promotes Therapeutic Resistance to Alkylating Agents
[ PUBLICATION ]
Alkylating agents are a first-line therapy for the treatment of several aggressive cancers, including pediatric glioblastoma, a lethal tumor in children. Unfortunately, many tumors are resistant to this therapy. We sought to identify ways of sensitizing tumor cells to alkylating agents while leaving normal cells unharmed, increasing therapeutic response while minimizing toxicity. Using an siRNA screen targeting over 240 DNA damage response genes, we identified novel sensitizers to ...
|Known for Alkylating Agents | Animal Drug Resistance | Ataxia Telangiectasia | Dna Glycosylase | Tumor Cells|
The role of drebrin in glioma migration and invasion
[ PUBLICATION ]
Glioblastoma (GBM) is the most common primary brain tumor in adults. Despite current advances in therapy consisting of surgery followed by chemotherapy and radiation, the overall survival rate still remains poor. Therapeutic failures are partly attributable to the highly infiltrative nature of tumor adjacent to normal brain parenchyma. Recently, evidence is mounting to suggest that actin cytoskeleton dynamics are critical components of the cell invasion process. Drebrin is an ...
|Known for Role Drebrin | Cell Motility | Brain Tumor | Actinbinding Protein | Actin Filament Organization|
The cofilin pathway plays a central role in the regulation of actin polymerization and the formation of cell membrane protrusions that are essential for cell migration. Overexpression of cofilin has been linked to the aggressiveness of a variety of different cancers. In these cancers, the phosphorylation of cofilin at Ser3 is a key regulatory mechanism modulating cofilin activity. The activation status of cofilin has been directly linked to tumor invasion. Accordingly, in this study, we ...
|Known for Cofilin Activity | Cell Migration | Activation Status | Local Invasiveness | Actin Polymerization|
Cdc42 is a Rho-GTPase which plays a major role in regulating cell polarity and migration by specifying the localization of filopodia. However, the role of Cdc42 in GBM invasion has not been thoroughly investigated. We generated stable doxycycline-inducible clones expressing wild type (WT)-, constitutively active (CA)-, and dominant negative (DN)-Cdc42 in three different human glioma cell lines. Expression of CA-Cdc42 significantly increased the migration and invasive properties of ...
|Known for Role Cdc42 | Cell Adhesion | Glioblastoma Multiforme | Malignant Gliomas | Migration Invasion|
Telomerase inhibition abolishes the tumorigenicity of pediatric ependymoma tumor-initiating cells
[ PUBLICATION ]
Pediatric ependymomas are highly recurrent tumors resistant to conventional chemotherapy. Telomerase, a ribonucleoprotein critical in permitting limitless replication, has been found to be critically important for the maintenance of tumor-initiating cells (TICs). These TICs are chemoresistant, repopulate the tumor from which they are identified, and are drivers of recurrence in numerous cancers. In this study, telomerase enzymatic activity was directly measured and inhibited to assess ...
|Known for Pediatric Ependymoma | Telomerase Activity | Alternative Lengthening | Maintenance Mechanisms | Cell Tumor|
Integrated (epi)-Genomic Analyses Identify Subgroup-Specific Therapeutic Targets in CNS Rhabdoid Tumors
[ PUBLICATION ]
We recently reported that atypical teratoid rhabdoid tumors (ATRTs) comprise at least two transcriptional subtypes with different clinical outcomes; however, the mechanisms underlying therapeutic heterogeneity remained unclear. In this study, we analyzed 191 primary ATRTs and 10 ATRT cell lines to define the genomic and epigenomic landscape of ATRTs and identify subgroup-specific therapeutic targets. We found ATRTs segregated into three epigenetic subgroups with distinct genomic ...
|Known for Rhabdoid Tumor | Differential Methylation | Epigenomic Analyses | Specific Therapeutic | Smarcb1 Protein|
Brian J Golbourn: Influence Statistics
|enhanced local migration||#6|
|lim kinasecofilin pathway||#6|
|fak neoplastic genes||#6|
|role activated cdc42||#6|
|cdc42 gbm invasion||#6|
|temporary bbb opening||#7|
|normal murine brainstem||#7|
|doxorubicin mrgfustreated animals||#7|
|mrgfus drug delivery||#7|
|cofilin cfl pathway||#8|
|gbm invasiveness phosphorylation||#8|
|cofilin regulating kinases||#8|
|gbm invasion genes||#8|
|dipg benzimidazoles blotting||#9|
|niraparib cell viability||#9|
|relative cell niraparib||#9|
|niraparib parp1 activity||#9|
|activated cdc42 binds||#9|
|niraparib dna damage||#9|
Key People For Aurora Kinase
Brian J Golbourn:Expert Impact
Concepts for whichBrian J Golbournhas direct influence:Aurora kinase, 3 medulloblastoma, Effective therapy, Tumor cell, Inbred nod mice, Pediatric ependymoma, Supratentorial ependymoma, Cofilin pathway.
Brian J Golbourn:KOL impact
Concepts related to the work of other authors for whichfor which Brian J Golbourn has influence:Focused ultrasound, Brain tumors, Rhabdoid tumor, Dna repair, Aurora kinase, Parp inhibitors, Glioblastoma cells.
Is this your profile? Claim your profile Copy URL Embed Link to your profile