Hepatoblastoma (HB) is the most common liver malignancy in children. The prognosis changes according to the histologic subtypes of HB. In the present study, we aimed to characterize the expression level of selected microRNAs (miRNAs) in HB as well as in histologic subtypes, and to consider the association with the prognosis. A total of 22 HB tumor samples, subtyped as fetal (n=16) and embryonal (n=6), and 10 nontumorous surrounding liver samples were evaluated in this study. Expressions of miR-17, miR-146a, miR-302d, and miR-19b were analyzed in 22 HB tumor samples and 10 nontumorous surrounding liver samples by quantitative real-time polymerase chain reaction. Lower miRNA-17 expression levels were obtained in tumor samples in comparison with nontumorous surrounding liver samples (P=0.028). Lower miRNA-17 expression was significant for predicting prognosis in HB patients (area under receiver-operator characteristic curve=0.875, P=0.044). A higher-level of miR-19b was found in embryonal samples (P=0.008). Overall and event-free survival was not found to correlate with miRNA expression levels (P>0.05). This research finds miRNA-17 and miRNA-19b expression levels can provide important data on diagnosis and prognosis in HB showing different clinical behaviors.
Aims: Ototoxicity is one of the main side effects of the chemotherapeutic agent Cisplatin (CDDP). CDDP ototoxicity is caused by damage of the organ of Corti, spiral ganglion cells or lateral wall (stria vascularis and spiral ligament). Mesenchymal stem cells (MSCs) were shown to differentiate into neurogenic and auditory hair cells in vitro. In this study, effect of MSCs in CDDP ototoxicity model of HEI-OC1 cochlear cells was evaluated.
Method:The cochlear cells were exposed to 50 and 100 microM CDDP for 24, 48, 72 hours with and without MSCs as coculture. The viability of the cells was analyzed with trypan blue dye and the percentage of apoptosis with Annexin-V by flow cytometer. The differentiation of MSCs to immature cochlear cells were shown by Math1, Calretinin and Myosin IIa immunohistochemistry.Results: At 100 microM dose, CDDP caused cytotoxicity on cochlear cells predominantly via necrosis. In co-culture, MSCs decreased cochlear cell damage of CDDP. In co-culture the ratio of Math1 and calretinin positive cells were increased supporting the idea of differentiation of MSCs into immature hair cells.
Conclusion:In this in vitro study, our data support that MSCs protects cochlear cells from CDDP cytotoxicity. MSC therapy might be a candidate cellular therapy approach to overcome CDDP ototoxicity. The mechanism seems to be via differentiation of MSCs into immature hair cells. Our next step is to plan in vivo nude mice neuroblastoma animal model comparing CDDP therapy with and without systemic MSC administration and check ototoxicity.
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