SUMOylation in Glioblastoma: A Novel Therapeutic Target.

Protein SUMOylation is a dynamic post-translational modification which is involved in a diverse set of physiologic processes throughout the cell. Of note, SUMOylation also plays a role in the pathobiology of a myriad of cancers, one of which is glioblastoma (GBM). Accordingly, herein, we review core aspects of SUMOylation as it relates to GBM and in so doing highlight putative methods/modalities capable of therapeutically engaging the pathway for treatment of this deadly neoplasm.

Aspiration of Subdural Hygroma Using Augmented Reality Neuronavigation: A Case Report.

Augmented reality (AR) is emerging as a key technology in neurosurgery. Projecting three-dimensional (3D) anatomic models onto the surgical field provides unique operative information to make procedures safer and more efficient. A small footprint, rapid registration AR system was used for bedside guidance during aspiration of a subdural hygroma. A 77-year-old male presented for resection of a suprasellar tumor and subsequently developed a large bilateral subdural hygroma. We performed the aspiration of the hygroma at the bedside using AR guidance. The AR system allowed for precise needle placement during the aspiration. The aim of this report was to demonstrate the clinical feasibility of integrating a novel AR system into the clinical workflow of a bedside procedure. As AR continues to expand in the field, the benefits of this technology for various procedures will become more evident.

Augmented Reality-Guided External Ventricular Drain Placement: A Case Report.

The placement of an external ventricular drain (EVD) is a critical neurosurgical procedure used to relieve intracranial pressure in patients with conditions such as hydrocephalus, traumatic brain injury, and intracranial hemorrhage. Traditional methods rely heavily on anatomical landmarks and the surgeon's experience, which can lead to variability in outcomes and increased risk of complications. Neuronavigation, while available, is infrequently used due to the size, cost, and set-up times associated with these devices. This report explores the use of a headset-based augmented reality (AR) system for guidance during the EVD placement procedure. We describe an AR system that overlays a 3D model of the patient's cranial anatomy, derived from preoperative imaging, onto the patient's head. This system is a head-mounted display and utilizes a rapid fiducial-less registration to provide the surgeon with visualization of 3D anatomy, and targeted trajectories. The system was used with a 32-year-old patient undergoing EVD placement prior to a cranioplasty. Due to the atypical cranial anatomy and due to prior procedures and midline shift, this relatively high-risk catheter placement was an ideal circumstance for the use of AR guidance during the EVD placement. This report described an early use of AR for EVD placement and represents a substantial advancement in neurosurgical practice, offering enhanced precision, efficiency, and safety. Further large-scale studies are warranted to validate these findings and explore the broader applicability of AR in other neurosurgical procedures.

Whole Sella vs Targeted Stereotactic Radiosurgery for Acromegaly: A Multicenter Matched Cohort Study.

BACKGROUND: Targeted stereotactic radiosurgery (SRS) with sparing of the residual pituitary is the traditional radiosurgical method for pituitary adenomas. Whole-sella SRS is an alternative choice for radiologically indeterminate or large adenomas, the safety and efficacy of which has yet to be determined. OBJECTIVE: To determine if whole-sella SRS in acromegaly would have comparable radiographic and biochemical control to targeted SRS. We performed a multicenter, retrospective matched cohort study to compare outcomes between groups. METHODS: We conducted a retrospective review of acromegalic patients who underwent SRS from 1990 to 2016 at 10 centers participating in the International Radiosurgery Research Foundation. Whole-sella and targeted SRS patients were then matched in a 1:1 ratio. RESULTS: A total of 128 patients were eligible for inclusion. Whole-sella patients had a higher pre-SRS random serum growth hormone, larger treatment volume, and higher maximum point dose to the optic apparatus. The rates of initial/durable endocrine remission, new loss of pituitary function, and new cranial neuropathy were similar between groups. Mortality and new visual deficit were higher in the whole-sella cohort, though not statistically significant. CONCLUSION: There was no difference in biochemical remission or recurrence between treatment groups. Although not statistically significant, the higher rates of tumor regression and lower rates of mortality and new visual deficit may suggest consideration of targeted SRS over whole-sella SRS in acromegaly treatment. Further research is needed to determine the association between visual deficits and mortality with whole-sella SRS.

Cauda equina syndrome in an ovarian malignant-mixed müllerian tumor with leptomeningeal spread.

Leptomeningeal metastasis is extremely rare in patients with ovarian cancer, but should be considered in patients presenting with neurologic deficits such as cauda equine syndrome. Given its poor prognosis and lack of data currently on management, additional studies are needed to optimize treatment regimens and improve outcomes.

Histone deacetylase inhibitor thailandepsin-A activates Notch signaling and suppresses neuroendocrine cancer cell growth in vivo.

Novel therapies for neuroendocrine (NE) cancers are desperately needed as they frequently present as metastatic disease and cause debilitating symptoms by secreting excessive hormones. Induction of Notch isoforms has a tumor suppressive effect in NE cancer cell lines, and we have observed that histone deacetylase inhibitors (HDACi) potently activate Notch. In this study, we describe the potential for Burkholderia thailandensis-derived class I HDACi thailandepsin A (TDP-A) as a Notch activator and therapeutic agent against NE cancer. IC50 for TDP-A was determined to be 4-6 nM in NE cancer cell lines (BON, MZ-CRC-1, and TT) without cytotoxicity to lung fibroblasts. The binding characteristics of TDP-A to its target HDAC1 was examined using bioluminescence resonance energy transfer (BRET). Western blot and flow cytometry analysis showed that TDP-A induces cell cycle arrest and apoptosis in a dose-dependent manner. TDP-A dose-dependently activated the Notch pathway as measured by increasing functional CBF1-luciferase reporter signal and mRNA and protein expressions of Notch isoforms, which were attenuated by pretreatment with γ-secretase inhibitor DAPT. Furthermore, TDP-A lead to changes in expression level of downstream targets of Notch pathway and reduced expression of NE cancer markers. An in vivo study demonstrated that TDP-A suppressed NE cancer progression. These results show that TDP-A, as a Notch activator, is a promising agent against NE cancers.