https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 Genome-wide association meta-analysis of single-nucleotide polymorphisms and symptomatic venous thromboembolism during therapy for acute lymphoblastic leukemia and lymphoma in caucasian children https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:39993 p < 5 x 10−8) in either cohort. Among the top 34 single-nucleotide polymorphisms (SNPs) (p < 1 x 10−6), two loci had concordant effects in both cohorts: ALOX15B (rs1804772) (MAF: 1%; p = 3.95 x 10−7) that influences arachidonic acid metabolism and thus platelet aggregation, and KALRN (rs570684) (MAF: 1%; p = 4.34 x 10−7) that has been previously associated with risk of ischemic stroke, atherosclerosis, and early-onset coronary artery disease. Conclusion: This represents the largest GWAS meta-analysis conducted to date associating SNPs to VTE in children and adolescents treated on childhood ALL protocols. Validation of these findings is needed and may then lead to patient stratification for VTE preventive interventions. As VTE hemostasis involves multiple pathways, a more powerful GWAS is needed to detect combination of variants associated with VTE.]]> Wed 20 Jul 2022 14:36:48 AEST ]]> TRIM16 inhibits proliferation and migration through regulation of interferon beta 1 in melanoma cells https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:18837 Wed 11 Apr 2018 15:08:53 AEST ]]> Histone deacetylase 2 and N-Myc reduce p53 protein phosphorylation at serine 46 by repressing gene transcription of tumor protein 53-induced nuclear protein 1 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:20844 TP53INP1 was found to be one of the genes most significantly repressed by HDAC2 and N-Myc according to Affymetrix microarray gene expression datasets. HDAC2 and N-Myc reduced TP53INP1 gene expression by direct binding to the TP53INP1 gene promoter, leading to transcriptional repression of TP53INP1, p53 protein de-phosphorylation at serine 46, neuroblastoma cell proliferation and survival. Moreover, low levels of TP53INP1 expression in human neuroblastoma tissues correlated with high levels of N-Myc expression and poor patient outcome, and the BET bromodomain inhibitors JQ1 and I-BET151 reduced N-Myc expression and reactivated TP53INP1 expression in neuroblastoma cells. These findings identify TP53INP1 repression as an important co-factor for N-Myc oncogenesis, and provide further evidence for the potential application of BET bromodomain inhibitors in the therapy of N-Myc-induced neuroblastoma.]]> Wed 11 Apr 2018 13:01:58 AEST ]]> A novel compound which sensitizes BRAF wild-type melanoma cells to vemurafenib in a TRIM16-dependent manner https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:25129 V600E/K mutation. In melanoma cells, loss of TRIM16 expression is a marker of cell migration and metastasis, while the BRAF inhibitor, vemurafenib, induces melanoma cell growth arrest in a TRIM16-dependent manner. Here we identify a novel small molecule compound which sensitized BRAF wild-type melanoma cells to vemurafenib. High throughput, cell-based, chemical library screening identified a compound (C012) which significantly reduced melanoma cell viability, with limited toxicity for normal human fibroblasts. When combined with the BRAFV600E/K inhibitor, vemurafenib, C012 synergistically increased vemurafenib potency in 5 BRAFWT and 4 out of 5 BRAFV600E human melanoma cell lines (Combination Index: CI < 1), and, dramatically reduced colony forming ability. In addition, this drug combination was significantly anti-tumorigenic in vivo in a melanoma xenograft mouse model. The combination of vemurafenib and C012 markedly increased expression of TRIM16 protein, and knockdown of TRIM16 significantly reduced the growth inhibitory effects of the vemurafenib and C012 combination. These findings suggest that the combination of C012 and vemurafenib may have therapeutic potential for the treatment of melanoma, and, that reactivation of TRIM16 may be an effective strategy for patients with this disease.]]> Thu 28 Oct 2021 12:37:19 AEDT ]]> The BET bromodomain inhibitor exerts the most potent synergistic anticancer effects with quinone-containing compounds and anti-microtubule drugs https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:27851 Thu 17 Mar 2022 14:39:27 AEDT ]]> Alterations in γ-actin and tubulin-targeted drug resistance in childhood leukemia https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:992 Sat 24 Mar 2018 08:29:50 AEDT ]]> Maternal folate and other vitamin supplementation during pregnancy and risk of acute lymphoblastic leukemia in the offspring https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:10268 Sat 24 Mar 2018 08:13:06 AEDT ]]> Effects of a novel long noncoding RNA, lncUSMycN, on N-Myc expression and neuroblastoma progression https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:20754 Sat 24 Mar 2018 08:00:25 AEDT ]]> Paternal intake of folate and vitamins B6 and B12 before conception and risk of childhood acute lymphoblastic leukemia https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:19855 Sat 24 Mar 2018 07:57:05 AEDT ]]> What about school?: educational challenges for children and adolescents with cancer https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:26709 Sat 24 Mar 2018 07:26:22 AEDT ]]> Persistent MRD before and after allogeneic BMT predicts relapse in children with acute lymphoblastic leukaemia https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:27000 50. A Cox multivariate regression model for LFS retained both B-other ALL subtype (hazard ratio 4·1, P = 0·0062) and MRD persistence post-HSCT (hazard ratio 3·9, P = 0·0070) as independent adverse prognostic variables. Persistent MRD could be used to direct post-HSCT therapy.]]> Sat 24 Mar 2018 07:25:49 AEDT ]]> Methotrexate-related central neurotoxicity: clinical characteristics, risk factors and genome-wide association study in children treated for acute lymphoblastic leukemia https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:44512 Fri 14 Oct 2022 09:11:36 AEDT ]]>