https://ogma.newcastle.edu.au/vital/access/ /manager/Index en-au 5 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:31071 CLU−/−) mice persisted after bleomycin and it was associated with increased DNA damage, reduced DNA repair responses, and elevated cellular senescence. Remarkably, this pattern mirrored that observed in IPF lung tissues. Together, our results show that cellular localization of Clusterin leads to divergent effects on epithelial cell regeneration and lung repair during fibrosis.]]> Wed 24 Nov 2021 15:51:40 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:49890 Wed 14 Jun 2023 17:16:17 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:15166 V600E melanoma cells to B-RAF inhibitors. Experimental Design: B-RAF^V600E melanoma cells were exposed to the B-RAF inhibitor PLX4720 for prolonged periods to select for cells resistant to apoptosis induced by the inhibitor. The resultant cells were analyzed for activation of extracellular signal regulated kinase (ERK), MAP/ERK kinase (MEK), and Akt, and related signals. Their roles in survival of the cells were also examined. Results: B-RAF^V600E melanoma cells selected for resistant to PLX4720-induced apoptosis retained the V600E mutation in B-RAF, and proliferated steadily in the presence of the inhibitor, albeit with slow growth rate. These cells displayed high levels of ERK activation, that is, at least in part, independent of the conventional RAF/MEK/ERK pathway, as MEK activation was low and inhibition of MEK did not significantly block activation of ERK. In contrast, extracellular signals appeared involved. This was associated with elevated activation of the phosphoinositide 3-kinase (PI3k)/Akt pathway and could be inhibited by serum starvation and inhibition of PI3k/Akt. Inhibition of MEK did not impact on survival of these cells, whereas serum starvation, inhibition of PI3K/Akt, and inhibition of ERK1/2 reduced their viability. Conclusions: These results indicate that sensitivity to induction of apoptosis may be a major determinant of long-term responses of B-RAF^V600E melanomas to specific inhibitors and suggest that rebound melanoma growth after initial treatment with the inhibitors may not be responsive to MEK inhibitors, but may be susceptible to inhibition of the PI3k/Akt pathway.]]> Wed 11 Apr 2018 16:15:39 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:6913 Wed 11 Apr 2018 15:38:21 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:18030 Wed 11 Apr 2018 14:49:14 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:22877 Wed 11 Apr 2018 13:19:11 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:14362 Wed 11 Apr 2018 12:28:38 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:14359 -ΔΔCt method was used to calculate the degree of expression. MTT assay showed the expression of miR-10b to have no effect on the proliferation of NPC cell lines. The wound healing assay showed that miR-10b mimics promoted the mobility and invasion of NPC cell lines. Inhibitors of miR-10b reduced the ability of NPC cell lines to migrate and invade. In addition, the expression of genes related to migration and invasion, such as E-cadherin, vimentin, and MMP-9, were confirmed to be different in the CNE-2Z NPC cell line transfected with miR-10b mimics and with miR-10b inhibitors. In the present study, miR-10b was found to upregulate the expression of MMP-9 and knockdown of miR-10b was found to significantly downregulate the expression of E-cadherin. On the whole, these results showed that miR-10b plays an important role in the invasion and metastasis of NPC cells.]]> Wed 11 Apr 2018 12:17:27 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:26547 in vitro and in vivo. PI staining showed significant apoptosis in NPC cells accompanied by the overproduction of ROS and downregulation of mitochondrial membrane potential (MMP, ΔΨm) by 3-BrPA. However, the ROS scavenger N-acetyl-L-cysteine (NAC) significantly reduced 3-BrPA-induced apoptosis by decreasing ROS and facilitating the recovery of MMP. We elucidated the molecular mechanisms underlying 3-BrPA activity and found that it caused mitochondrial dysfunction and ROS production, leading to necroptosis of NPC cells. We investigated the effects of the caspase inhibitor z-VAD-fmk, which inhibits apoptosis but promotes death domain receptor (DR)-induced NPC cell necrosis. Necrostatin-1 (Nec-1) inhibits necroptosis, apparently via a DR signaling pathway and thus abrogates the effects of z-VAD‑fmk. In addition, we demonstrated the effective attenuation of 3-BrPA-induced necrotic cell death by Nec-1. Finally, animal studies proved that 3-BrPA exhibited significant antitumor activity in nude mice. The present study is the first demonstration of 3-BrPA-induced non-apoptotic necroptosis and ROS generation in NPC cells and provides potential strategies for developing agents against apoptosis‑resistant cancers.]]> Wed 11 Apr 2018 11:05:32 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:14383 Wed 11 Apr 2018 09:49:12 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:30132 Wed 09 Feb 2022 15:54:15 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:46558 Tue 07 Nov 2023 11:36:39 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:31285 Thu 28 Oct 2021 12:36:57 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:24957 in vivo and assessed for possible clinical applications.]]> Thu 27 Jan 2022 15:58:35 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:25166 Thu 03 Feb 2022 12:22:19 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:10447 Sat 24 Mar 2018 08:08:03 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:19089 Sat 24 Mar 2018 08:05:24 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:17365 Sat 24 Mar 2018 08:01:31 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:18033 Sat 24 Mar 2018 07:56:32 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:18006 Sat 24 Mar 2018 07:56:16 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:22689 Streptomyces hygroscopicus. In the present study, we examined the anticancer effects of 17-DR on human hepatocellular carcinoma (HCC) cell lines HepG2 and SMMC7721, and its underlying mechanisms. The results indicated that 17-DR could concentration-dependently inhibit the proliferation, and decrease the colony formation in HCC cells. It also induced significant apoptosis in HCC cells, which was mediated by mitochondria via a caspase-dependent pathway. The mechanisms involved in 17-DR-induced apoptosis included the downregulation of myeloid cell leukemia-1 (Mcl-1), and upregulation of Bcl-2 antagonist killer 1 (Bak). And the upregulated Bak expression resulted from downregulation of Mcl-1 played an essential role in this process. Taken together, these results indicated that 17-DR possessed potent anticancer effects on HCC cells by inhibiting cell proliferation and inducing apoptosis.]]> Sat 24 Mar 2018 07:11:11 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:44872 Mon 24 Oct 2022 11:16:47 AEDT ]]>