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...

PURPOSE: To investigate whether tissue factor (TF) regulates fibroblast growth factor (FGF)-2-induced angiogenesis in retinoblastoma. METHODS: In an orthotopic transplantation mouse model of retinoblastoma, immunofluorescence staining for TF and CD31 (an endothelial cell maker) was performed. With treatment of FGF-2 (10 ng/ml), TF expression in human umbilical vein endothelial cells (HUVECs) was measured by Western blotting. To confirm the role of TF in tumor angiogenesis in retinoblastoma, anti-angiogenic activity of TF pathway inhibitor (TFPI) was investigated by treating TFPI on FGF-2-induced proliferation, migration and in vitro tube formation of HUVECs. In addition, inhibition of ERK1/2 phosphorylation by TFPI was measured by Western blot analysis. RESULTS: TF was highly expressed on vascular endothelial cells of retinoblastoma, co-localized with CD31. With FGF-2-induced proliferation of HUVECs, TF expression was significantly up-regulated. Interestingly, TFPI effectively inhibited FGF-2-induced proliferation, migration and in vitro tube formation of HUVECs, which was accompanied by inhibition of ERK1/2 phosphorylation. CONCLUSIONS: TF is involved in tumor angiogenesis of retinoblastoma via extracellular signal-regulated kinase pathway.

Since the beginning of the 1990s, palaeontologists have been interested in understanding biological processes recorded within the bone microstructure of deinonychosaurian theropods, the group comprising Troodontidae and Dromaeosauridae. Several studies were published on this subject, and the growing database requires the first revision of used terminology and older interpretations. Furthermore, a platform correlating the developmental characters of all investigated taxa is missing. Hence, we lack a perspective to evaluate the potential of deinonychosaurian osteohistology for understanding their evolution and that of their close relatives, including avialans. This study aimed to fill in this gap by offering a comprehensive review of the previous osteohistological investigations published on deinonychosaurians and Archaeopteryx. Four significant evolutionary phenomena are assumed from the investigated deinonychosaurian taxa: (1) it is likely that troodontids evolved general osteohistology closer to basal avialans than to dromaeosaurids, (2) in troodontids, reticular vasculature is correlated to maturation timing, (3) the first growth deceleration occurs later in smaller deinonychosaurs (e.g. Changyuraptor, Sinornithosaurus) than in larger forms (e.g. Buitreraptor), and (4) the growth rate of the deinonychosaurs' hind limbs might be correlated with a specific type of locomotion.