ZD55-shMYCN provides a novel agent for treating MYCN-amplified and p53-inactive aggressive neuroblastoma, representing a promising approach for further clinical development.
Neuroblastoma is among the most aggressive tumors that occur in childhood and infancy. The clinical prognosis of children with advanced-stage neuroblastoma is still poor. Interleukin-24 (IL-24) is emerging as a new cytokine involved in tumor cellular proliferation, differentiation, and apoptosis and has been widely studied as a tumor inhibitor. However, little is known about this cytokine's role in neuroblastoma. In this study, we investigated the possible effects of IL-24 on inducing neuroblastoma cell differentiation, growth inhibition, and apoptosis in vitro. Our data show that IL-24 promotes neuroblastoma SH-SY5Y cell differentiation, growth inhibition, and apoptosis. Furthermore, we found that the differentiation- and apoptosis-inducing action of IL-24 depends on the accumulation of reactive oxygen species (ROS). These results suggest that IL-24 can induce neuroblastoma cell differentiation and apoptosis and may be a potential therapeutic agent for neuroblastoma.
The amplification of MYCN is a typical characteristic of aggressive neuroblastomas, whereas acquired mutations of p53 lead to refractory and relapsed cases. We had previously examined the applicability of the replication-competent oncolytic adenovirus, ZD55-shMYCN, to deliver a short hairpin RNA targeting MYCN gene for p53-null and MYCN-amplified neuroblastoma cell line LA1-55N. Our data have shown that ZD55-shMYCN has an additive tumor growth inhibitory response through shRNA-mediated MYCN knockdown and ZD55-mediated cancer cell lysis. In this regard, ZD55-shMYCN can downregulate MYCN and perform anticancer effects, thereby acquiring significance in the administration of MYCN-amplified and p53-null neuroblastomas. Hence, we further investigated the anticancer properties of ZD55-shMYCN in neuroblastomas. Our data showed that ZD55-shMYCN induced G2/M arrest via decreasing the levels of cyclin D1 and cyclin B1 irrespective of p53 status. ZD55-shMYCN effectively induced apoptosis in neuroblastomas through activation of caspase-3 and enhancing PARP cleavage. Furthermore, ZD55-shMYCN could downregulate phosphoinositide 3-kinase and pAkt and upregulate RKIP levels. Similarly, pro-apoptosis was revealed by the histopathologic examination of paraffin-embedded section of resected tumors of mice xenograft. In vitro and in vivo studies, we elucidate the apoptosis properties and mechanisms of action of ZD55-shMYCN, which provide a promising approach for further clinical development.
To compare a novel modified W-incision scrotoplasty (MWS) operation method with the conventional V-Y scrotoplasty for treatment of severe penoscrotal webbing (PSW) in children a retrospective study was conducted on 26 children. Circumcision combined with modified scrotoplasty was used to repair the webbed penis and phimosis of children and another 32 patients undergoing V-Y scrotoplasty served as the control group. There was a statistically significant difference of angle improvements of penis and scrotum in a horizontal position (−66 ± 10; −57 ± 6, P < 0.001) and the parent satisfaction score (Five Likert Scale) (4.7 ± 0.56; 3.8 ± 0.47, P < 0.001) between the two groups. All 26 children who underwent MWS presented with no serious postoperative complications, and there was no significant difference in surgical complications compared to children treated with V-Y scrotoplasty.
The aim of the study was to summarize the preliminary experience of minimally invasive open nephrectomy operation on children with multicystic dysplastic kidney (MCDK). A retrospective review was performed on the clinical materials of the 15 children that had accepted consecutive minimally invasive open nephrectomies during the previous 2 years. The enrolled children were diagnosed with unilateral MCDK under computed tomography, emission computerized tomography and ultrasound and no anomaly in the contralateral functioning kidney was found. Of the 15 children, 12 were boys and 3 were girls, with 5 cases on the right and 10 cases on the left. Operations were completed at the retroperitoneal space in order to open an incision on the waists and ribs of the children, the length of which ranged from 1.5 to 2.0 cm (average 1.7 cm). The age of the children at operation ranged from 3 months to 5.6 years old, with an average of 2.4 years old. Surgery lasted for 30–50 min, with an average of 34.6 min. The estimated blood loss of each child was <5 ml. After operation, prophylactic intravenous antibiotics were administered for 2–4 days to prevent infection. All of the operations proved very successful. Following surgery the children were hospitalized for 2–4 days for observation, with an average of 2.8 days. No complications occurred during the follow-up period. In conclusion, minimally invasive open nephrectomy is effective for children with MCDK. The procedure is superior with regard to operative time, cosmesis, and length of stay. It is a safe and effective treatment choice for patietns with MCDK and can be easily performed on children.
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