Medulloblastoma (MB) is the most common children brain cancer. Recent advances in cancer biology strMBongly suggest that impaired microRNAs expression is one of the critical events driving cancer development. Previous studies of microRNA expression profiling suggested hsa-miR-383 as one of the down-regulated microRNAs in MB. However, the functions of this microRNA in MB remain unclear. In this study, we demonstrated frequent down-regulation of hsa-miR-383 expression in MB by quantitative stem-loop-RT-PCR analysis. Twenty-three out of 29 (79%) MB samples expressed .2-fold of the lower level of hsa-miR-383 compared with normal cerebellar samples and also limited/ non-detectable levels were found in 4 MB cell lines (DAOY, ONS-76, D283, and D458). Ectopic expression of hsa-miR-383 by microRNA mimic significantly inhibited MB cell growth along with increase of PARP cleavage, suggesting induction of apoptosis in the hsa-miR-383-mimic-treated MB cells and tumor suppressive roles of hsa-miR-383. By transcriptome analysis of hsa-miR-383-mimic-treated MB cells and computational prediction of hsa-miR-383 targets, we identified Peroxiredoxin 3 (PRDX3) as one of the targets with significant downregulation of expression in the mimic-treated MB cells. Down-regulation was verified at both RNA and protein levels. In addition, the mimic significantly reduced luciferase activity of the reporter that was constructed with the 3'UTR of PRDX3 in MB cells. Site-directed mutation of the predicted recognition site abrogated the reduction, and this demonstrated the specificity of hsa-miR-383-mediated repression on PRDX3 expression in MB cells. Furthermore, siRNA knockdown of PRDX3 resulted in cell growth inhibition and induction of PARP cleavage, mimicking the effects of the hsa-miR-383 restoration by microRNA mimic in MB cells. In conclusion, hsa-miR-383 may function as tumor suppressive microRNA in MB and this is mediated through its target PRDX3 to control MB cell growth. Centro di Riferimento Oncologico, Aviano, Italy BACKGROUND: A prospective intensive chemo-radiotherapy trial was launched for ncPNET. After introducing HDCT, we amended CSI to focal RT for selected cases. METHODS: From 1997 to 2010 we enrolled 25 consecutive patients in a pre-radiation schedule cointaining HDMTX, HDVP16, HDCTX and HDCBDCA, followed by HART-CSI at total doses 31-39 Gy, implemented with 2 hd thiotepa courses following CSI after the first 5 patients. Six children received the same chemotherapy but only focal RT at 54 Gy. RESULTS: 16 were males, median age was 7 years. Median follow-up was 42 mos (11-152). 5year PFS and OS were 56% and 47%, respectively, being PFS 80% for pineal tumors (n 10) vs 43% for other sites (p 0.05). Residual disease (n 22), metastases (4), response to pre-RT CT were not prognostically significant. Patients receiving HDCT had a PFS of 64% vs 37.5% (p 0.09). Response to RT in children with residual tumor was MB-02. QUESTIONABLE ROLE OF CRANIOSPINAL IRRADIATION (CSI) IN NON CEREBELLAR PNET(NCPNET) WHEN USING A HIGH-DOSE CHEMOTHERAPY...

No abstract