https://nova.newcastle.edu.au/vital/access/ /manager/Index en-au 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:30268 Wed 23 Feb 2022 16:06:20 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:30575 Wed 20 Mar 2019 12:05:15 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:48900 Wed 19 Apr 2023 16:40:13 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:20299 Wed 11 Apr 2018 16:54:44 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:19023 V600E or MEK downregulated Noxa, whereas activation of MEK/ERK caused its upregulation. In addition, introduction of BRAF^V600E increased Noxa expression in melanocytes. Upregulation of Noxa was due to a transcriptional increase mediated by cAMP responsive element binding protein, activation of which was also increased by MEK/ERK signaling in melanoma cells. Significantly, Noxa appeared necessary for constitutive activation of autophagy, albeit at low levels, by MEK/ERK in melanoma cells. Furthermore, it was required for autophagy activation that delayed apoptosis in melanoma cells undergoing nutrient deprivation. These results reveal that oncogenic activation of MEK/ERK drives Noxa expression to promote autophagy, and suggest that Noxa has an indirect anti-apoptosis role in melanoma cells under nutrient starvation conditions.]]> Wed 11 Apr 2018 16:41:25 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:27772 Wed 11 Apr 2018 15:54:06 AEST ]]> https://nova.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 ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:28036 Wed 11 Apr 2018 12:47:04 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:28215 Wed 02 Mar 2022 14:25:48 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:46696 in vitro system that can be used to evaluate other IVDD therapies.]]> Tue 29 Nov 2022 09:49:28 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:27776 Thu 28 Oct 2021 13:04:26 AEDT ]]> https://nova.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 BRAF^V600E/K inhibitor, vemurafenib, C012 synergistically increased vemurafenib potency in 5 BRAF^WT and 4 out of 5 BRAF^V600E 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 ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:27851 Thu 17 Mar 2022 14:39:27 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:54816 Thu 14 Mar 2024 14:38:44 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:33474 Thu 03 Feb 2022 12:18:02 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:51497 A (p.P.A148T) and survival of patients with bladder or kidney cancer remains controversial. Materials and Methods: We compared the allele frequencies of NOD2 c.3020insC and CDKN2A p.A148T allele in 706 patients with bladder cancer, 410 cases with kidney cancer against two control groups. The Cox proportional hazards model was used to determine whether there were any survival differences between carriers of the NOD2 c.3020insC or the CDKN2A p.A148T variant. Results: Among the three patient subgroups: patients under 60 years of age, non-smokers and a third with histological features of low grade noninvasive papillary bladder cancer, we observed that the c.3020insC allele had a nominal statistically significant effect on survival. We also observed that the NOD2 c.3020insC variant was more frequent in patients with bladder cancer aged between 51 and 60 years. There was some nominal evidence that the CDKN2A p.A148T polymorphism reduced survival in the subgroup of bladder cancer patients under 60 years of age. We observed that in kidney cancer patients, the incidence of the NOD2 variant appeared to be lower in the group aged between 60 and 70 years, however, this was not statistically significant. In addition, in patients with histological features of grade III chromophobic kidney cancer, the c.3020insC allele also appeared to be overrepresented but this too was not statistically significant. Conclusion: We have shown that the NOD2 c.3020insC allele and the CDKN2A p.A148T polymorphism does not play a role in the survival of patients with bladder cancer.]]> Fri 08 Sep 2023 11:56:10 AEST ]]>