Translational research : the journal of laboratory and clinical medicine
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Oncolytic virotherapy is a therapeutic approach that uses replication-competent viruses to kill cancers. The ability of oncolytic viruses to selectively replicate in cancer cells leads to direct cell lysis and induction of anticancer immune response. ⋯ This review provides an insight into the different characteristics of oncolytic viruses (natural and genetically modified) that contribute to effective applications of oncolytic virotherapy in preclinical and clinical trials, and strategies to overcome the limitations. The potential of oncolytic virotherapy combining with other conventional treatments or cancer immunotherapies involving immune checkpoint inhibitors and CAR-T therapy could form part of future multimodality treatment strategies.
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The 7 members of the A3 family of cytidine deaminases (A3A to A3H) share a conserved catalytic activity that converts cytidines in single-stranded (ss) DNA into uridines, thereby inducing mutations. After their initial identification as cell-intrinsic defenses against HIV and other retroviruses, A3s were also found to impair many additional viruses. Moreover, some of the A3 proteins (A3A, A3B, and A3H haplotype I) are dysregulated in cancer cells, thereby causing chromosomal mutations that can be selected to fuel progression of malignancy. ⋯ Two independent lines of evidence supported the conclusion that the multiprotein CRLpVHL complex is necessary for A3 degradation. CRLpVHL more effectively induced degradation of nuclear, procancer A3 (A3B) than the cytoplasmic, antiretroviral A3 (A3G). These results identify specific cellular factors that regulate A3s post-translationally.
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Neuroblastoma (NB) is the most common extracranial pediatric solid cancer originating from undifferentiated neural crest cells. NB cells express EZH2 and GLI1 genes that are known to maintain the undifferentiated phenotype of cancer stem cells (CSC) in NB. Recent studies suggest that tumor-derived extracellular vesicles (EVs) can regulate the transformation of surrounding cells into CSC by transferring tumor-specific molecules they contain. ⋯ Using these models, we observed an enrichment of GLI1 and EZH2 mRNAs in NB-derived EVs. As a consequence of the uptake of NB-derived EVs, the host cells increased the expression levels of GLI1 and EZH2. These results suggest the alteration of the expression profile of stromal cells through an EV-based mechanism, and point the GLI1 and EZH2 mRNAs in the EV cargo as diagnostic biomarkers in NB.
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The microRNAs (miRNAs) that can regulate diabetic kidney disease (DKD) have not been fully characterized. The aim of this study was to identify the miRNAs that affect DKD and could be used as specific biomarkers or therapeutic agents. First, kidney tissues from two DKD mouse models and control mice were screened for differences in miRNA expression by microarray analysis followed by quantitative real-time reverse transcription-PCR. ⋯ Furthermore, the serum level of miRNA-125b-5p was significantly higher in patients with DKD (1.89±0.40-fold, P<0.05) compared with patients with other kidney diseases (0.94±0.13-fold) and healthy subjects (1.00±0.19-fold). Serum levels of miRNA-181b-5p were lower in patients with DKD (0.30±0.06-fold, P<0.05) compared with patients with other kidney diseases (1.06±0.20-fold) and healthy subjects (1.00±0.16-fold). These results suggest that miRNA-125b-5p and miRNA-181b-5p may represent novel diagnostic biomarkers and that miRNA-181b-5p may represent a therapeutic target for DKD.
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Review
Immune responses to injury and their links to eye disease: Immune responses to wounding in the eye.
The eye is regarded as an immune privileged site. Since the presence of a vasculature would impair vision, the vasculature of the eye is located outside of the central light path. As a result, many regions of the eye evolved mechanisms to deliver immune cells to sites of dysgenesis, injury, or in response to the many age-related pathologies. ⋯ The response to traumatic or pathological injury is distinct in different regions of the eye. Age-related diseases impact both the anterior and posterior segment and lead to reduced quality of life and blindness. Here we focus attention on the role that inflammation and fibrosis play in the progression of age-related pathologies of the cornea and the lens as well as in glaucoma, the formation of epiretinal membranes, and in proliferative vitreoretinopathy.