Epstein–Barr virus (EBV) lytic induction therapy is an emerging virus-targeted therapeutic approach that exploits the presence of EBV in tumor cells to confer specific killing effects against EBV-associated malignancies. Efforts have been made in the past years to uncover the mechanisms of EBV latent-lytic switch and discover different classes of chemical compounds that can reactivate the EBV lytic cycle. Despite the growing list of compounds showing potential to be used in the lytic induction therapy, only a few are being tested in clinical trials, with varying degrees of success. This review will summarize the current knowledge on EBV lytic reactivation, the major hurdles of translating the lytic induction therapy into clinical settings, and highlight some potential strategies in the future development of this therapy for EBV-related lymphoid and epithelial malignancies.
The development of the CNS in vertebrate embryos involves the generation of different sub-types of neurons and glia in a complex but highly-ordered spatio-temporal manner. Zebrafish are commonly used for exploring the development, plasticity and regeneration of the CNS, and the recent development of reliable protocols for isolating and culturing neural stem/progenitor cells (NSCs/NPCs) from the brain of adult fish now enables the exploration of mechanisms underlying the induction/specification/differentiation of these cells. Here, we refined a protocol to generate proliferating and differentiating neurospheres from the entire brain of adult zebrafish. We demonstrated via RT-qPCR that some isoforms of ip3r, ryr and stim are upregulated/downregulated significantly in differentiating neurospheres, and via immunolabelling that 1,4,5-inositol trisphosphate receptor (IP3R) type-1 and ryanodine receptor (RyR) type-2 are differentially expressed in cells with neuron- or radial glial-like properties. Furthermore, ATP but not caffeine (IP3R and RyR agonists, respectively), induced the generation of Ca transients in cells exhibiting neuron- or glial-like morphology. These results indicate the differential expression of components of the Ca-signaling toolkit in proliferating and differentiating cells. Thus, given the complexity of the intact vertebrate brain, neurospheres might be a useful system for exploring neurodegenerative disease diagnosis protocols and drug development using Ca signaling as a read-out.
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