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Abstract: Mutations and/or overexpression of c-Kit proto-oncogene frequently occur in subsets of acute myeloid leukemia (AML) and contribute to abnormal cell proliferation and poor outcomes. We showed that c-Kit expression was subject to post-transcriptional regulation by microRNA (miRNA)-193b. Notably, miR-193b was significantly down-regulated in the examined AML cells and its levels were inversely correlated with c-Kit levels. Restoration of miR-193b expression in AML cells resulted in distinctly reduced c-Kit expression and inhibited cell growth. These data reveal a role for miR-193b dysregulation in myeloid leukemogenesis and the therapeutic promise of regulating miR-193b expression for c-Kit-positive AML. [Copyright &y& Elsevier]

Abstract: NK cells as a component of the innate immune system provide a first line of defense against viral infections and malignancies. Killer immunoglobulin-like receptors (KIRs) are a polymorphic gene family expressed on NK cells. The crucial role of DNA methylation in determining the variegated expression pattern of KIRs has recently been reported. In this study the direct effect of DNA demethylating treatment on human NK cell cytotoxicity was analyzed. In a human NK cell line NK-92MI, inhibitory KIR genes exhibited characteristic epigenetic repression, whose promoter regions are densely methylated. Treatment of NK-92MI cells with methyltransferase inhibitor 5-azacytidine significantly increased the expression levels of inhibitory KIRs and strongly suppressed their cytolytic activity against human K562 leukemic cells. Cytolytic activity of human polyclonal NK cells was also suppressed upon 5-azacytidine-treatment. The suppression of NK cell cytotoxicity was associated with 5-azacytidine-induced overexpression of inhibitory KIRs and impaired granzyme B and perforin release by these cells. The results demonstrate for the first time that demethylating treatment can suppress NK cell cytolytic activity. The aberrant methylation patterns of KIR genes during NK cell differentiation and maturation may have importance for its abnormal function. [Copyright &y& Elsevier]

Background S100A4 gene product has been implicated in tumor invasion and metastasis. The overall survival rate of children with neuroblastoma remains poor because of disease dissemination at the time of diagnosis. The purpose of this study was to investigate the effect and mechanism of S100A4 on invasion and metastasis of neuroblastoma. Methods A 20-mer phosphorothioate antisense oligodeoxynucleotide (asODN) targeted against the S100A4 mRNA was transfected into the human neuroblastoma cell line LA-N-6 by Lipofectamine 2000. The expressions of S100A4 and MMP-2 mRNAs were quantified by the reverse transcription polymerase chain reaction. The capability of migration and invasion of LA-N-6 cells were evaluated by the transwell chamber assay. Results The S100A4 mRNA and the MMP-2 mRNA levels in asODN-treated cells were decreased by 35.6% and 25.5%, respectively, compared with those in nontreated cells. The numbers of migrating and invading LA-N-6 cells were both significantly lower in the asODN-treated groups than those in the nontreated groups ( 9.33 ± 4.73 vs 20.67 ± 2.89 and 2.33 ± 1.15 vs 9.00 ± 2.65, respectively; both P = .03 ). Conclusions The S100A4 asODN significantly reduced the S100A4 mRNA levels and the motility and invasive ability of neuroblastoma cells, with concomitant decrease of the MMP-2 mRNA levels. Thus, S100A4 may exert its effect on invasion and metastasis of neuroblastoma cells by stimulating the motility of tumor cells as well as influencing the expression of MMP-2. [ABSTRACT FROM AUTHOR]

An optimized Enhanced Recovery After Surgery (ERAS) program is lacking for adolescent idiopathic scoliosis (AIS). The aim of the present study was to evaluate the impact and feasibility of an optimized ERAS pathway in patients with surgically treated AIS. In total, 79 patients with AIS who underwent corrective surgery without 3-column osteotomy were recruited from Xijing Hospital of the Fourth Military Medical University between 2012 and 2018. Forty-four patients were treated according to a traditional protocol and 35 were managed using an optimized ERAS pathway, which was designed and implemented by a multidisciplinary team. The following data were collected and retrospectively analyzed, demographic characteristics, Cobb angle, curve type (Lenke), surgical duration, fusion level, correction rate, estimated blood loss, postoperative hemoglobin level, postoperative pain score, pain relief time, hemovac drainage, drainage removal time, first ambulation time, length of hospital stay, and postoperative complications. There was no significant difference between the traditional and ERAS groups with respect to demographic characteristics, Cobb angle, curve type (Lenke), fusion level, and correction rate. However, the ERAS group had a shorter surgical duration, less blood loss and hemovac drainage, a higher postoperative hemoglobin level, and earlier pain relief, ambulation, and discharge. The rates of postoperative nausea and vomiting were lower in the ERAS group than in the traditional group. The ERAS pathway is capable of improving the perioperative status of patients with AIS by offering stronger analgesia, faster ambulation, and earlier discharge. [ABSTRACT FROM AUTHOR]