In the field of molecular oncology, microRNAs (miRNAs) and their role in regulating physiological processes and cancer pathogenesis have been a revolutionary discovery over the last decade. It is now considered that miRNA dysregulation influences critical molecular pathways involved in tumor progression, invasion, angiogenesis and metastasis in a wide range of cancer types. Hence, altering miRNA levels in cancer cells has promising potential as a therapeutic intervention, which is discussed in many other articles in this Special Issue. Some of the most significant hurdles in therapeutic miRNA usage are the stability and the delivery system. In this review, we cover a comprehensive update on the challenges and strategies for the development of therapeutic miRNA delivery systems that includes virus-based delivery, non-viral delivery (artificial lipid-based vesicles, polymer-based or chemical structures), and recently emerged extracellular vesicle (EV)-based delivery systems.

This study suggested that most PSTs would contain a small fraction of SP cells (possible stem-like population). Targeting the CSC will provide a novel treatment strategy to eradicate refractory PSTs.

Introduction: Patch closure is necessary to achieve tension-free repair in

Neuroblastoma (NB) is a highly metastatic tumor in children. The epithelial-mesenchymal transition (EMT) is an important mechanism for both the initiation of tumor invasion and subsequent metastasis. This study investigated the role of EMT in the progression of NB. Using EMT assays on samples from 11 tumors, we identified 14 genes that were either differentially expressed between tumors of different stages or highly upregulated in NB. Quantitative RT-PCR of these genes was conducted in 96 NB tumors and their expression levels were compared between stages and between tumors with the presence and absence of MYCN amplification. The association of survival rate with differential gene expression was investigated. Expression of KRT19 was significantly decreased in stage 3 or 4 NB as well as stage 4S NB compared with stage 1 or 2 NB. Expression levels of KRT19 and ERBB3 were significantly low, and expression levels of TWST1 and TCF3 were high in MYCN-amplified NB. The patients with low expression of KRT19 or ERBB3 showed significantly worse overall survival. Furthermore, the correlation between high invasive ability and low expression of KRT19 and ERBB3 was suggested in vitro using six NB cell lines. The authors conclude that downregulation of KRT19 is highly associated with tumor progression in NB and metastasis in localized primary NB and that low expression of ERBB3 is also associated with progression of NB.

Recently, tissue engineering of the autologous esophagus has been thought to provide a promising strategy for esophageal substitution. In this study, gastric acellular matrix (GAM) was used as a scaffold for regeneration of the esophagus in a rat model. Usage of GAM has an advantage that naturally derived extracellular matrix autograft can be prepared less invasively in a clinical setting. Twenty-seven F344 female rats were used as recipients. Patch defects created in the abdominal esophagus were replaced by GAM patch grafts. The rats were sacrificed 1 week to 18 months after implantation. The specimen was examined macroscopically as well as microscopically. 5'-Bromo-2'-deoxyuridine (BrdU) proliferation assay was performed in six rats that were sacrificed 1, 2, and 4 weeks after implantation. Twenty-four rats survived without complications. The graft site did not show esophageal stenosis or dilatation in any rat. Keratinized stratified squamous esophageal mucosa was regenerated in the entire graft 2 weeks after implantation. Regeneration of the muscle layer or lamina muscularis mucosae in the graft site was not observed even 18 months after implantation. Marked incorporation of BrdU was observed only in the mucosal layer but not in the muscle layer. GAM patch graft provided satisfactory mucosal regeneration of the esophagus without stenosis or dilatation, although muscle regeneration was still a future challenge.

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