Development and optimisation of in vitro sonodynamic therapy for glioblastoma.

Sonodynamic therapy (SDT) is currently on critical path for glioblastoma therapeutics. SDT is a non-invasive approach utilising focused ultrasound to activate photosensitisers like 5-ALA to impede tumour growth. Unfortunately, the molecular mechanisms underlying the therapeutic functions of SDT remain enigmatic. This is primarily due to the lack of intricately optimised instrumentation capable of modulating SDT delivery to glioma cells in vitro. Consequently, very little information is available on the effects of SDT on glioma stem cells which are key drivers of gliomagenesis and recurrence. To address this, the current study has developed and validated an automated in vitro SDT system to allow the application and mapping of focused ultrasound fields under varied exposure conditions and setup configurations. The study optimizes ultrasound frequency, intensity, plate base material, thermal effect, and the integration of live cells. Indeed, in the presence of 5-ALA, focused ultrasound induces apoptotic cell death in primary patient-derived glioma cells with concurrent upregulation of intracellular reactive oxygen species. Intriguingly, primary glioma stem neurospheres also exhibit remarkably reduced 3D growth upon SDT exposure. Taken together, the study reports an in vitro system for SDT applications on tissue culture-based disease models to potentially benchmark the novel approach to the current standard-of-care.

Sacral ependymoma presents 20 years after initial posterior fossa lesion.

Posterior fossa ependymomas (PFEs) are designated histologically as low-grade neoplasms. Despite being characterised as benign, cases of metastasis have been reported only a few times with the patients concurrently diagnosed with the primary tumour. Interval drop metastasis or spontaneous second distal tumours are extremely rare and, in most cases, are diagnosed within a few months of primary tumour resection. Here, we report a patient with a grade 2 paediatric PFE exhibiting a 20-year interval to a second sacral ependymoma. The patient was initially diagnosed with a PFE at the age of 10 years and underwent tumour resection and postoperative radiotherapy. In their late 20s, the patient presented with basilar artery occlusion complicated by life-threatening epistaxis. Post-thrombolysis, the patient presented with a large sacral grade 1 myxopapillary ependymoma with cauda equina syndrome-like symptoms. Here, we present a rare case of two ependymomas with a 20-year interval in the same patient with compounding comorbidities.