Novel Pannexin 1 isoform is increased in cancer.

Pannexin 1 (PANX1) is upregulated in many cancers, where its activity and signalling promote tumorigenic properties. Here, we report a novel ∼25 kDa isoform of human PANX1 (hPANX1-25K) which lacks the N-terminus and was detected in several human cancer cell lines including melanoma, osteosarcoma, breast cancer and glioblastoma multiforme. This isoform was increased upon CRISPR/Cas9 deletion targeting the first exon near M1, suggesting a potential alternative translation initiation (ATI) site.

Spatiotemporally dynamic electric fields for brain cancer treatment: aninvestigation.

. The treatment of glioblastoma (GBM) using low intensity electric fields (∼1 V cm) is being investigated using multiple implanted bioelectrodes, which was termed intratumoral modulation therapy (IMT). Previous IMT studies theoretically optimized treatment parameters to maximize coverage with rotating fields, which required experimental investigation.

Development of Brain-Derived Bioscaffolds for Neural Progenitor Cell Culture.

Biomaterials derived from brain extracellular matrix (ECM) have the potential to promote neural tissue regeneration by providing instructive cues that can direct cell survival, proliferation, and differentiation. This study focused on the development and characterization of microcarriers derived from decellularized brain tissue (DBT) as a platform for neural progenitor cell culture. First, a novel detergent-free decellularization protocol was established that effectively reduced the cellular content of porcine and rat brains, with a >97% decrease in the dsDNA content, while preserving collagens (COLs) and glycosaminoglycans (GAGs).

Planning system for the optimization of electric field delivery using implanted electrodes for brain tumor control.

Background: The use of non-ionizing electric fields from low-intensity voltage sources (< 10 V) to control malignant tumor growth is showing increasing potential as a cancer treatment modality. A method of applying these low-intensity electric fields using multiple implanted electrodes within or adjacent to tumor volumes has been termed as intratumoral modulation therapy (IMT).

Purpose: This study explores advancements in the previously established IMT optimization algorithm, and the development of a custom treatment planning system for patient-specific IMT.

Cranial nerve and intramedullary spinal malignant peripheral nerve sheath tumor associated with neurofibromatosis-1.

Background: Malignant peripheral nerve sheath tumors (MPNSTs) are uncommon but aggressive neoplasms associated with radiation exposure and neurofibromatosis Type I (NF1). Their incidence is low compared to other nervous system cancers, and intramedullary spinal lesions are exceedingly rare. Only a few case reports have described intramedullary spinal cord MPNST.

Optimization of multi-electrode implant configurations and programming for the delivery of non-ablative electric fields in intratumoral modulation therapy.

Purpose: Application of low intensity electric fields to interfere with tumor growth is being increasingly recognized as a promising new cancer treatment modality. Intratumoral modulation therapy (IMT) is a developing technology that uses multiple electrodes implanted within or adjacent tumor regions to deliver electric fields to treat cancer. In this study, the determination of optimal IMT parameters was cast as a mathematical optimization problem, and electrode configurations, programming, optimization, and maximum treatable tumor size were evaluated in the simplest and easiest to understand spherical tumor model.

Expanding the search for genetic biomarkers of Parkinson's disease into the living brain.

Altered gene expression related to Parkinson's Disease (PD) has not been described in the living brain, yet this information may support novel discovery pertinent to disease pathophysiology and treatment. This study compared the transcriptome in brain biopsies obtained from living PD and Control patients. To evaluate the novelty of this data, a comprehensive literature review also compared differentially expressed gene (DEGs) identified in the current study with those reported in PD cadaveric brain and peripheral tissues.

Response to commentary on "the middle fossa approach with self-drilling screws: a novel technique for BONEBRIDGE implantation".

The aim of this letter is to respond to a commentary on a published article on the middle fossa approach to BONEBRIDGE implantation with self-drilling screws published by the senior authors.

The middle fossa approach with self-drilling screws: a novel technique for BONEBRIDGE implantation.

Background: Bone conduction implants can be used in the treatment of conductive or mixed hearing loss. The BONEBRIDGE bone conduction implant (BB-BCI) is an active, transcutaneous device. BB-BCI implantation can be performed through either the transmastoid or retrosigmoid approach with their respective limitations.

Diffuse intrinsic pontine glioma cells are vulnerable to low intensity electric fields delivered by intratumoral modulation therapy.

Introduction: Diffuse intrinsic pontine glioma (DIPG) is a high fatality pediatric brain cancer without effective treatment. The field of electrotherapeutics offers new potential for other forms of glioma but the efficacy of this strategy has not been reported for DIPG. This pilot study evaluated the susceptibility of patient-derived DIPG cells to low intensity electric fields delivered using a developing technology called intratumoral modulation therapy (IMT).

Preclinical outcomes of Intratumoral Modulation Therapy for glioblastoma.

Glioblastoma (GBM) is the leading cause of high fatality cancer arising within the adult brain. Electrotherapeutic approaches offer new promise for GBM treatment by exploiting innate vulnerabilities of cancer cells to low intensity electric fields. This report describes the preclinical outcomes of a novel electrotherapeutic strategy called Intratumoral Modulation Therapy (IMT) that uses an implanted stimulation system to deliver sustained, titratable, low intensity electric fields directly across GBM-affected brain regions.

Staged multi-modality treatment approaches for giant cerebellopontine angle hemangioblastomas.

Giant hemangioblastomas (HBs) located in the cerebellopontine angle (CPA) present rare, high risk neurosurgical challenges. En bloc resection has been traditionally recommended for HBs, however this approach may pose unacceptable risk with giant tumors. Alternative treatment strategies have not been well described and the relevant literature is scant.

Direct motor evoked potentials and cortical mapping using the NIM® nerve monitoring system: A technical note.

Motor evoked potentials (MEPs) are commonly used to prevent neurological injury when operating in close proximity to the motor cortex or corticospinal pathway. We report a novel application of the NIM® nerve monitoring system (Medtronic@ NIM response 3.0) for intraoperative direct cortical (dc)-MEPs monitoring.

Advances in HSP27 and HSP90-targeting strategies for glioblastoma.

Glioblastoma (GBM) is the most common and malignant primary brain tumor in adults. There is a critical need for novel strategies to abolish the molecular mechanisms that support GBM growth, invasion and treatment resistance. The heat shock proteins, HSP27 and HSP90, serve these pivotal roles in tumor cells and have been identified as effective targets for developing therapeutics.

In Vitro Validation of Intratumoral Modulation Therapy for Glioblastoma.

Background/aim: This proof-of-concept study evaluated the antitumor impact of a direct electrical stimulation technique, termed intratumoral modulation therapy (IMT) on glioblastoma (GBM) cells.

Materials And Methods: An in vitro IMT model comprised of a calibrated electrode to deliver continuous, low-intensity stimulation within GBM preparations. Viability and apoptosis assays were performed in treated immortalized and patient-derived GBM cells, and post-mitotic neurons.

Cerebellar liponeurocytoma: a rare intracranial tumor with possible familial predisposition. Case report.

The biological origin of cerebellar liponeurocytomas is unknown, and hereditary forms of this disease have not been described. Here, the authors present clinical and histopathological findings of a young patient with a cerebellar liponeurocytoma who had multiple immediate family members who harbored similar intracranial tumors. A 37-year-old otherwise healthy woman presented with a history of progressive headaches.

Advances in Neurotrophic Factor and Cell-Based Therapies for Parkinson's Disease: A Mini-Review.

Parkinson's disease (PD) affects an estimated 7-10 million people worldwide and remains without definitive or disease-modifying treatment. There have been many recent developments in cell-based therapy (CBT) to replace lost circuitry and provide chronic biological sources of therapeutic agents to the PD-affected brain. Early neural transplantation studies underscored the challenges of immune compatibility, graft integration and the need for renewable, autologous graft sources.

HSP27 knockdown produces synergistic induction of apoptosis by HSP90 and kinase inhibitors in glioblastoma multiforme.

Background/aim: The heat-shock proteins HSP27 and HSP90 perpetuate the malignant nature of glioblastoma multiforme (GBM) and offer promise as targets for novel cancer therapeutics. The present study sought to define synergistic antitumor benefits of concurrent HSP27-knockdown and the HSP90 inhibitor, 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) or, comparatively, the non-selective kinase inhibitor, staurosporine, in GBM cells.

Materials And Methods: Dose-response relations were determined for 17-AAG and staurosporine in three GBM cell lines.

Neurotrophic factor expression in expandable cell populations from brain samples in living patients with Parkinson's disease.

Cell-based therapies offer promise for patients with Parkinson's disease (PD); however, durable and effective transplantation substrates need to be defined. This study characterized the feasibility and growth properties of primary cultures established from small-volume brain biopsies taken during deep brain stimulation (DBS) surgery in patients with PD. The lineage and expression of neurotrophic factors with known beneficial actions in PD-affected brain circuitry were also evaluated.

Perioperative ischemic complications of the brain after carotid endarterectomy.

Background: The potential morbidity of cerebral ischemia after carotid endarterectomy (CEA) has been recognized, but its reported incidence varies widely.

Objective: To prospectively evaluate the development of cerebral ischemic complications in patients treated by CEA at a high-volume cerebrovascular center.

Methods: Fifty patients with moderate or severe carotid stenosis awaiting CEA were studied with perioperative diffusion-weighted imaging of the brain and standardized neurological evaluations.

Lateral transpeduncular approach to intrinsic lesions of the rostral pons.

Objective: We describe the lateral transpeduncular approach to access lesions in the rostral pons. The surgical indications and technique are discussed in the context of an illustrative case and pertinent anatomic considerations.

Methods: A 38-year-old man with acute right hemiparesis and bulbar symptoms had a left pontine hemorrhage with an associated cavernous malformation and venous anomaly.

Sustained relief of dystonia following cessation of deep brain stimulation.

We describe the unusual clinical course of a patient with cranial dystonia (i.e., Meige syndrome) and additional upper limb involvement, who developed sustained relief of motor symptoms following cessation of a prolonged course of bilateral pallidal deep brain stimulation (DBS).

Development of a provincial guideline for the acute assessment and management of adult and pediatric patients with head injuries.

Background: Regionalized approaches to trauma care improve patient outcomes. We developed and distributed a clinical reference poster to standardize the emergency department evaluation and management of patients with traumatic head injuries in hospitals throughout Nova Scotia.

Methods: We conducted a MEDLINE literature search to identify publications in the fields of prehospital and emergency management of head injuries.

Impaired percent alpha variability on continuous electroencephalography is associated with thalamic injury and predicts poor long-term outcome after human traumatic brain injury.

Continuous electroencephalography (cEEG) is potentially useful in determining prognosis in patients with traumatic brain injuries (TBI). The objective of this prospective, observational cohort study was to determine if the percent alpha variability (PAV) on cEEG was predictive of outcome following TBI. Injury characteristics were indexed to assess whether lesions in specific cerebral loci were correlated with PAV and patient recovery.

Enhanced expression of heat shock protein 27 is correlated with axonal regeneration in mature retinal ganglion cells.

The small heat shock protein, Hsp27, promotes axonal regeneration in peripheral neurons; however, an analogous role in the central nervous system has not been described. This study examined the relationship between Hsp27 expression and regeneration in mature retinal ganglion cells (RGCs). Adult rat optic nerves were transected and exposed to peripheral nerve autografts to stimulate regeneration of cut RGC axons.