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BACKGROUND We have previously shown that MYCN knockdown causes a G1 arrest in MYCN amplified (MNA), p53 wild type (wt) and p53 mutant MNA neuroblastoma cell lines, with increases in p21(WAF1) and hypo RB in p53 wt cell lines. HYPOTHESIS MYCN acts by inhibiting p21(WAF1), and also by p21(WAF1) independent mechanisms to override the G1 checkpoint in(More)
p53 mutations have been reported in cell lines derived from relapsed neuroblastoma tumors. We hypothesize that functional inactivation of p53 by mutation or other mechanisms is common in relapsed neuroblastoma and can contribute to chemoresistance. Our aim was to determine the frequency of p53 mutations, p14(ARF) methylation, or deletion and MDM2(More)
The MYCN oncogene encodes a transcription factor which is amplified in up to 40% of high risk neuroblastomas. MYCN amplification is a well-established poor prognostic marker in neuroblastoma, however the role of MYCN expression and the mechanisms by which it acts to promote an aggressive phenotype remain largely unknown. This review discusses the current(More)
PURPOSE Targeting BET proteins was previously shown to have specific antitumoral efficacy against MYCN-amplified neuroblastoma. We here assess the therapeutic efficacy of the BET inhibitor, OTX015, in preclinical neuroblastoma models and extend the knowledge on the role of BRD4 in MYCN-driven neuroblastoma. EXPERIMENTAL DESIGN The efficacy of OTX015 was(More)
Pyrimidine metabolism is a major route for therapeutic intervention against malaria. Here we report inhibition and structural studies on the deoxyuridine nucleotidohydrolase from the malaria parasite Plasmodium falciparum (PfdUTPase). We have identified a series of triphenylmethane derivatives of deoxyuridine with antimalarial activity in vitro which(More)
A chimera comprising the N-terminal region of the human alpha7 nicotinic acetylcholine receptor, fused to the transmembrane/C-terminal domains of the mouse serotonin 5-HT3 receptor, was constructed. Injection of the chimera cDNA into Xenopus oocytes, or transient transfection in human embryonic kidney (HEK-293) cells, resulted in the expression of(More)
We previously reported that 3 p53 wild type (wt) MYCN amplified (MNA) neuroblastoma cell lines failed to G1 arrest after DNA damage despite induction of p53, p21(WAF1) and MDM2. We hypothesised that this was due to high MYCN expression. p53 responses to DNA damage were examined in an additional 13 p53 wt neuroblastoma cell lines. MNA was significantly(More)
Background:The current biomarkers alpha-fetoprotein and human chorionic gonadotropin have limited sensitivity and specificity for diagnosing malignant germ-cell tumours (GCTs). MicroRNAs (miRNAs) from the miR–371–373 and miR–302/367 clusters are overexpressed in all malignant GCTs, and some of these miRNAs show elevated serum levels at diagnosis. Here, we(More)
The overexpression of secreted proteins is of critical importance to the biotechnology and biomedical fields. A common roadblock to high yields of proteins is in the endoplasmic reticulum (ER) where proofreading for properly folded proteins is often rate limiting. Heterologous expression of secreted proteins can saturate the cell's capacity to properly fold(More)
p53 mutations have been reported in cell lines derived from relapsed neuroblastoma tumors. We hypothesize that functional inactivation of p53 by mutation or other mechanisms is common in relapsed neuroblastoma and can contribute to chemoresistance. Our aim was to determine the frequency of p53 mutations, p14 methylation, or deletion and MDM2 amplification(More)