Glioblastoma (GBM) is characterized by extremely poor prognoses, despite the use of gross surgical resection, alkylating chemotherapeutic agents, and radiotherapy. Evidence increasingly highlights the role of the tumor microenvironment in enabling this aggressive phenotype. Despite this interest, the role of neurotransmitters, brain-specific messengers underlying synaptic transmission, remains murky. These signaling molecules influence a complex network of molecular pathways and cellular behaviors in many CNS-resident cells including neural stem cells and progenitor cells, neurons, and glia cells. Critically, available data convincingly demonstrate that neurotransmitters can influence proliferation, quiescence, and differentiation status of these cells. This ability to affect progenitors and glia—GBM-initiating cells—and their availability in the CNS, strongly support the notion that neurotransmitters participate in the onset and progression of GBM. This review will focus on dopamine and serotonin, as studies indicate they contribute to gliomagenesis. Particular attention will be paid to how these neurotransmitters and their receptors can be utilized as novel therapeutic targets. Overall, this review will analyze the complex biology governing the interaction of GBM with neurotransmitter signaling and highlight how this interplay shapes the aggressive nature of GBM.

Oncolytic virotherapy for cancer is an innovative therapeutic option where the ability of a virus to promote cell lysis is harnessed and reprogrammed to selectively destroy cancer cells. Such treatment modalities exhibited antitumor activity in preclinical and clinical settings and appear to be well tolerated when tested in clinical trials. However, the clinical success of oncolytic virotherapy has been significantly hampered due to the inability to target systematic metastasis. This is partly due to the inability of the therapeutic virus to survive in the patient circulation, in order to target tumors at distant sites. An early study from various laboratories demonstrated that cells infected with oncolytic virus can protect the therapeutic payload form the host immune system as well as function as factories for virus production and enhance the therapeutic efficacy of oncolytic virus. While a variety of cell lineages possessed potential as cell carriers, copious investigation has established stem cells as a very attractive cell carrier system in oncolytic virotherapy. The ideal cell carrier desire to be susceptible to viral infection as well as support viral infection, maintain immunosuppressive properties to shield the loaded viruses from the host immune system, and most importantly possess an intrinsic tumor homing ability to deliver loaded viruses directly to the site of the metastasis—all qualities stem cells exhibit. In this review, we summarize the recent work in the development of stem cell-based carrier for oncolytic virotherapy, discuss the advantages and disadvantages of a variety of cell carriers, especially focusing on why stem cells have emerged as the leading candidate, and finally propose a future direction for stem cell-based targeted oncolytic virotherapy that involves its establishment as a viable treatment option for cancer patients in the clinical setting.

Glioblastoma (GBM) is the most common primary brain malignancy in adults, with a 100% recurrence rate and 21-month median survival. Our lab and others have shown that GBM contains a subpopulation of glioma stem cells (GSCs) that expand during chemotherapy and may contribute to therapeutic resistance and recurrence in GBM. To investigate the mechanism behind this expansion, we applied gene set expression analysis (GSEA) to patient-derived xenograft (PDX) cells in response to temozolomide (TMZ), the most commonly used chemotherapy against GBM. Results showed significant enrichment of cancer stem cell and cell cycle pathways (False Discovery Rate (FDR) < 0.25). The ligand of numb protein 1 (LNX1), a known regulator of Notch signaling by targeting negative regulator Numb, is strongly upregulated after TMZ therapy (p < 0.0001) and is negatively correlated with survival of GBM patients. LNX1 is also upregulated after TMZ therapy in multiple PDX lines with concomitant downregulations in Numb and upregulations in intracellular Notch1 (NICD). Overexpression of LNX1 results in Notch1 signaling activation and increased GSC populations. In contrast, knocking down LNX1 reverses these changes, causing a significant downregulation of NICD, reduction in stemness after TMZ therapy, and resulting in more prolonged median survival in a mouse model. Based on this, we propose that during anti-GBM chemotherapy, LNX1-regulated Notch1 signaling promotes stemness and contributes to therapeutic resistance.

A lumboperitoneal shunt facilitates dynamic flow of cerebrospinal fluid into the peritoneum. Consequently, neuraxial technique placement in the parturient with a lumboperitoneal shunt can result in unexpected levels of blockade. We present the case of a parturient with a lumboperitoneal shunt who experienced symptoms consistent with high blockade after epidural administration of 450 mg chloroprocaine. This report emphasizes potential mechanisms for high neuraxial blockade and strategies to decrease risks in this unique patient population.

Purpose: To use validated outcome measures to evaluate the clinical results of surgical repair of distal triceps tendon ruptures using transosseous tunnels and high‐strength sutures with proximally based knots. Methods: A consecutive series of traumatic distal triceps tendon ruptures at a single institution was studied. All cases were surgically repaired by 1 surgeon using high‐strength suture with a bone tunnel–based repair technique. Repair knots were oriented proximally instead of in the traditional distal position. All patients were evaluated at long‐term follow‐up with a physical examination performed by the orthopaedic surgeon and the following validated outcome measures: Disabilities of the Arm, Shoulder and Hand score; Mayo Elbow Performance Score; and visual analog scale score. Results: Seven male patients with a mean age of 38 years (range, 19‐50 years) and mean follow‐up period of 4.1 ± 1.2 years underwent distal triceps tendon repair with bone tunnels and high‐strength sutures with proximally positioned knots. Of the repairs, 4 involved the dominant arm. At final follow‐up, the mean Disabilities of the Arm, Shoulder and Hand score was 1.3 ± 3.1; the mean Mayo Elbow Performance Score was 99.3 ± 1.9; and the mean visual analog scale score was 0. One additional patient who declined participation in the study had wound dehiscence and infection with an associated partial rerupture. Conclusions: This case series of triceps tendon repairs using transosseous tunnels and proximally based knots showed favorable postoperative elbow function based on validated outcome measures. Level of Evidence: Level IV, therapeutic case series.