https://nova.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 AEBP1 upregulation confers acquired resistance to BRAF (V600E) inhibition in melanoma https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:14360 Wed 11 Apr 2018 17:15:26 AEST ]]> Cotargeting histone deacetylases and oncogenic BRAF synergistically kills human melanoma cells by necrosis independently of RIPK1 and RIPK3 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:14354 V600E melanoma cells by induction of necrosis. Cotreatment with the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) or panobinostat (LBH589) and the BRAF inhibitor PLX4720 activated the caspase cascade, but caspases appeared dispensable for killing, in that inhibition of caspases did not invariably block induction of cell death. The majority of dying cells acquired propidium iodide positivity instantly when they became positive for Annexin V, suggesting induction of necrosis. This was supported by caspase-independent release of high-mobility group protein B1, and further consolidated by rupture of the plasma membrane and loss of nuclear and cytoplasmic contents, as manifested by transmission electron microscopic analysis. Of note, neither the necrosis inhibitor necrostatin-1 nor the small interference RNA (siRNA) knockdown of receptor-interacting protein kinase 3 (RIPK3) inhibited cell death, suggesting that RIPK1 and RIPK3 do not contribute to induction of necrosis by combinations of HDAC and BRAF inhibitors in BRAFV600E melanoma cells. Significantly, SAHA and the clinically available BRAF inhibitor vemurafenib cooperatively inhibited BRAFV600E melanoma xenograft growth in a mouse model even when caspase-3 was inhibited. Taken together, these results indicate that cotreatment with HDAC and BRAF inhibitors can bypass canonical cell death pathways to kill melanoma cells, which may be of therapeutic advantage in the treatment of melanoma.]]> Wed 11 Apr 2018 17:05:48 AEST ]]> Macrophage migration inhibitory factor engages PI3K/Akt signalling and is a prognostic factor in metastatic melanoma https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:20455 Wed 11 Apr 2018 16:49:10 AEST ]]> Regulation of apoptosis induced by targeting the RAF/MEK/ERK pathway in human melanoma https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:15254 Wed 11 Apr 2018 16:23:04 AEST ]]> Reactivation of ERK and Akt confers resistance of mutant BRAF colon cancer cells to the HSP90 inhibitor AUY922 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:28215 Wed 02 Mar 2022 14:25:48 AEDT ]]> Pharmacodynamic effects and mechanisms of resistance to Vemurafenib in patients with metastatic melanoma https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:20093 Sat 24 Mar 2018 08:00:06 AEDT ]]> Targeted therapy in melanoma: the era of personalized medicine https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:19810 Sat 24 Mar 2018 07:57:12 AEDT ]]> Therapeutic targeting of heat shock protein 90 in human colon cancer cells https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:33805 Mon 23 Sep 2019 12:49:49 AEST ]]> Activating kinase mutations in melanoma https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:13257 Fri 07 Dec 2018 16:28:48 AEDT ]]>