There is growing evidence that astrocytes play critical roles in neuron-glial interactions at the synapse. Astrocytes are believed to regulate presynaptic and postsynaptic structures and functions, in part, by the release of gliotransmitters such as glutamate, ATP, and D-serine; however, little is known of how neurons and astrocytes communicate to regulate these processes. Here, we investigated a family of transmembrane proteins called ephrinBs and Eph receptors that are expressed in the synapse and are known to regulate synaptic transmission and plasticity. In addition to their presence on CA1 hippocampal neurons, we determined that ephrins and Eph receptors are also expressed on hippocampal astrocytes. Stimulation of hippocampal astrocytes with soluble ephrinB3, known to be expressed on CA1 postsynaptic dendrites, enhanced D-serine synthesis and release in culture. Conversely, ephrinB3 had no effect on D-serine release from astrocytes deficient in EphB3 and EphA4, which are the primary receptors for ephrinB3. Eph receptors mediate this response through interactions with PICK1 (protein interacting with C-kinase) and by dephosphorylating protein kinase C ␣ to activate the conversion of L-serine to D-serine by serine racemase. These findings are supported in vivo, where reduced D-serine levels and synaptic transmissions are observed in the absence of EphB3 and EphA4. These data support a role for ephrins and Eph receptors in regulating astrocyte gliotransmitters, which may have important implications on synaptic transmission and plasticity.

Brachytherapy (BT) for glioblastoma multiforme (GBM) involves the use of radioactive isotopes to deliver ionizing radiation directly into the tumor bed. Its application as a means to prolong survival in GBM patients over the past few decades has come with variable success. The objective of this review is to describe the utility of BT in GBM, and to report the outcomes and adverse events associated with its use in different multimodal treatment approaches. A search of the literature was conducted using the PubMed database. The most recent search was performed in September 2015. Thirty-two series involving 1571 patients were included in our review. The longest median overall survival (MOS) following BT for newly diagnosed GBM reached 28.5 months. Overall, 1-, 2-, and 3-year survival rates were 46-89 %, 20-57 %, and 14-27 %. For recurrent GBM, the longest reported MOS after BT was 15.9 months. One-, 2- and 3-year survival rates for recurrent GBM were 10-66 %, 3-23 %, and 9-15 %. Adverse events were reported in 27 % of patients. Reoperation for radiation necrosis occurred in 4 and 27 % of patients following low- and high-dose rate BT, respectively. BT is a feasible option for extending survival in carefully selected GBM patients. As patient outcomes and overall survival improve with more aggressive radiotherapy, so does the risk of radiation-related complications. The most effective use of BT is likely as a part of multimodal treatment with other novel therapies.

Interplay effects in highly modulated stereotactic body radiation therapy lung cases treated with volumetric modulated arc therapy. Purpose: To evaluate the influence of tumor motion on dose delivery in highly modulated stereotactic body radiotherapy (SBRT) of lung cancer using volumetric modulated arc therapy (VMAT). Methods: 4D-CT imaging data of the quasar respiratory phantom were acquired, using a GE Lightspeed 16-slice CT scanner, while the phantom reproduced patient specific respiratory traces. Flattening filter-free (FFF) dual-arc VMAT treatment plans were created on the acquired images in Pinnacle 3 treatment planning system. Each plan was generated with varying levels of complexity characterized by the modulation complexity score. Static and dynamic measurements were delivered to Gaf-Chromic EBT3 film inside the respiratory phantom using an Elekta Versa HD linear accelerator. The treatment prescription was 10 Gy per fraction for 5 fractions. Comparisons of the planned and delivered dose distribution were performed using Radiological Imaging Technology (RIT) software. Results: For the motion amplitudes and periods studied, the interplay effect is insignificant to the GTV coverage. The mean dose deviations between the planned and delivered dose distribution never went below −2.00% and a minimum dose difference of −5.05% was observed for a single fraction. However for amplitude of 2 cm, the dose error could be as large as 20.00% near the edges of the PTV at increased levels of complexity. Additionally, the modulation complexity score showed an ability to provide information related to dose delivery. A correlation value (R) of 0.65 was observed between the complexity score and the gamma passing rate for GTV coverage. Conclusions: As expected, respiratory motion effects are most evident for large amplitude respirations, complex fields, and small field margins. However, under all tested conditions target coverage was maintained.

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