CAR T Cell Therapy for Pediatric Brain Tumors.

Chimeric Antigen Receptor (CAR) T cell therapy has recently begun to be used for solid tumors such as glioblastoma multiforme. Many children with pediatric malignant brain tumors develop extensive long-term morbidity of intensive multimodal curative treatment. Others with certain diagnoses and relapsed disease continue to have limited therapies and a dismal prognosis. Novel treatments such as CAR T cells could potentially improve outcomes and ameliorate the toxicity of current treatment. In this review, we discuss the potential of using CAR therapy for pediatric brain tumors. The emerging insights on the molecular subtypes and tumor microenvironment of these tumors provide avenues to devise strategies for CAR T cell therapy. Unique characteristics of these brain tumors, such as location and associated morbid treatment induced neuro-inflammation, are novel challenges not commonly encountered in adult brain tumors. Despite these considerations, CAR T cell therapy has the potential to be integrated into treatment schema for aggressive pediatric malignant brain tumors in the future.

Surgical Treatment of Symptomatic Small Medial Petrous Meningiomas Causing Trigeminal Neuralgia.

BACKGROUND: Symptomatic trigeminal neuralgia caused by small (<3 cm) skull base meningiomas is treated by radiosurgery or surgical resection. Although radiosurgery is less invasive, surgical resection provides more rapid resolution of symptoms. We reviewed a short series of patients who underwent an anterior transpetrosal approach for surgical resection of meningiomas causing trigeminal neuralgia. METHODS: A retrospective review of 5 consecutive patients with meningiomas causing trigeminal neuralgia of the senior author was included. Preoperative parameters (size, proximity to critical neurovascular structures, presence of brainstem compression), intraoperative parameters (Simpson grade of resection, loss of brainstem evoked potentials, surgical approach), and outcomes (symptom resolution, extent of resection, follow-up) were recorded. RESULTS: Patient median age was 67 years (range, 60-73 years). All patients had symptoms concerning trigeminal neuralgia with 2 having associated areas of facial numbness. The anterior transpetrosal approach was used to achieve complete resection (Simpson grade I). Postresection, the trigeminal nerve and brainstem were clearly visible to evaluate neurovascular structures and ensure decompression. No postoperative complications were reported, and all patients experienced sustained symptomatic relief 1 month postsurgery. CONCLUSIONS: With the advent of radiosurgery for skull base meningiomas, surgical resection is not always considered; however, such meningiomas causing trigeminal neuralgia can be resected safely using the anterior transpetrosal approach allowing rapid resolution of symptoms. This review of operative nuances provides a guide for neurosurgeons to provide safe surgical resection.

Molecular events in MSC exosome mediated cytoprotection in cardiomyocytes.

A host of hormonal-metabolic alterations take place following exposure of cardiomyocytes to hypoxia and other noxious stimuli. Here, we demonstrate that exposure of cultured rat cardiomyocytes to lipopolysaccharide (LPS) resulted in upregulation (~1.5 fold) of oxidized low-density lipoprotein receptor-1 (LOX-1). There was also a marked increase in apoptosis 12 hrs after LPS treatment with caspase-3 levels being significantly elevated (~1.3 fold) and a significant increase in LDH release at 24 hrs. Interestingly, there was a ~1.4-fold upregulation of LC-3 expression post-LPS treatment indicating development of autophagy, which probably is a compensatory response to combat cellular injury induced by LPS. Treatment with LPS also reduced the size and morphology of cardiomyocyte spheroids. In an attempt to limit LPS-induced injury, cardiomyocytes were treated with exosomes derived from mesenchymal stromal cells (MSCs). We noted a significant suppression of LOX-1 expression that in turn suppressed apoptosis as well as autophagic response and restored spheroid morphology. Mass spectrophotometric analysis of MSC exosomes revealed a cargo rich in proteins which are involved in pathways negatively modulating cell death and apoptosis while promoting cell survival. This is first report to our knowledge on the initial molecular events in MSC exosome mediated cytoprotection of stressed cardiomyocytes.