https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:50220 Wed 28 Feb 2024 15:47:57 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:47696 Wed 25 Jan 2023 08:57:08 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:47540 Wed 24 Jan 2024 15:22:27 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:31299 Wed 23 Feb 2022 16:01:26 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:37515 Wed 23 Aug 2023 09:36:21 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:30575 Wed 20 Mar 2019 12:05:15 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:37757 ARF in human and p19^ARF in mouse) that binds to and inhibits mouse double minute 2 homolog (MDM2) leading to p53 activation, whereas p53 suppresses c-Myc through a combination of mechanisms involving transcriptional inactivation and microRNA-mediated repression. Nonetheless, the regulatory interactions between c-Myc and p53 are not retained by cancer cells as is evident from the often-imbalanced expression of c-Myc over wildtype p53. Although p53 repression in cancer cells is frequently associated with the loss of ARF, we disclose here an alternate mechanism whereby c-Myc inactivates p53 through the actions of the c-Myc-Inducible Long noncoding RNA Inactivating P53 (MILIP). MILIP functions to promote p53 polyubiquitination and turnover by reducing p53 SUMOylation through suppressing tripartite-motif family-like 2 (TRIML2). MILIP upregulation is observed amongst diverse cancer types and is shown to support cell survival, division and tumourigenicity. Thus our results uncover an inhibitory axis targeting p53 through a pan-cancer expressed RNA accomplice that links c-Myc to suppression of p53.]]> Wed 17 Nov 2021 16:28:34 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:50273 Wed 12 Jul 2023 14:18:12 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:52417 Wed 11 Oct 2023 11:58:33 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:20455 Wed 11 Apr 2018 16:49:10 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:1383 Wed 11 Apr 2018 15:51:49 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:13811 Wed 11 Apr 2018 15:41:21 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:19242 Wed 11 Apr 2018 12:53:35 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:14353 Wed 11 Apr 2018 11:50:58 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:27771 In vitro, breast cancer cells were able to induce neurite outgrowth in PC12 cells, and this neurotrophic activity was partially inhibited by anti-NGF blocking antibodies. In conclusion, infiltration by nerve fibers is a feature of the tumor microenvironment that is associated with aggressiveness and involves NGF production by cancer cells. The potential participation of nerve fibers in breast cancer progression needs to be further considered.]]> Wed 11 Apr 2018 11:44:48 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:16805 Wed 11 Apr 2018 11:29:15 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:9196 Wed 11 Apr 2018 10:54:31 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:5046 Wed 11 Apr 2018 10:25:08 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:18028 Wed 11 Apr 2018 09:44:48 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:49273 Wed 10 May 2023 12:10:31 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:32181 Wed 09 Mar 2022 15:58:36 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:36867 NTR, and the proneurotrophin receptor sortilin were analyzed with immunohistochemistry in a cohort of thyroid cancers (n = 128) and compared with adenomas and normal thyroid tissues (n = 62). TrkA was detected in 20% of thyroid cancers, compared with none of the benign samples (P = 0.0007). TrkA expression was independent of histologic subtypes but associated with lymph node metastasis (P = 0.0148), suggesting the involvement of TrkA in tumor invasiveness. Nerves in the tumor microenvironment were positive for TrkA. p75^NTR was overexpressed in anaplastic thyroid cancers compared with papillary and follicular subtypes (P < 0.0001). Sortilin was overexpressed in thyroid cancers compared with benign thyroid tissues (P < 0.0001). Neurotrophin receptor expression was confirmed in a panel of thyroid cancer cell lines at the mRNA and protein levels. Functional investigations using the anaplastic thyroid cancer cell line CAL-62 found that siRNA against TrkA, p75^NTR, and sortilin decreased cell survival and cell migration through decreased SRC and ERK activation. Together, these data reveal TrkA, p75^NTR, and sortilin as potential therapeutic targets in thyroid cancer.]]> Wed 09 Feb 2022 15:52:42 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:41023 Wed 08 Nov 2023 09:37:41 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:39074 Wed 04 May 2022 15:24:42 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:51136 Tue 22 Aug 2023 15:58:29 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:37665 2 ≥ 0.997). However, TruCount beads produced the most consistent (concentration variation = 3.8%) calculated numbers of plasma CD41⁺/Annexin V⁺ MV, which were significantly higher from that calculated using either Flow-Count or CountBright (p < 0.001). The FACSCanto was able to resolve 0.5 μm beads by FSC and 0.16 μm beads by SSC, but there were significantly more background events using SSC compared with FSC (3113 vs. 470; p = 0.008). In general, sample analysis by SSC resulted in significantly higher numbers of MV (p < 0.0001) but was well correlated with enumeration by FSC for all MV subtypes (ρ = 0.62–0.89, p < 0.0001). We conclude that all counting beads provided linear results at concentrations ranging from 6 beads/μl to 100 beads/μl, but TruCount was the most consistent. Using SSC to gate MV events produced high background which negatively affected counting bead enumeration and overall MV calculations. Strategies to reduce SSC background should be employed in order to reliably use this technique.]]> Tue 09 Mar 2021 18:12:55 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:34397 in vitro. Notably, only the first eluted MP fraction bound HK₂ cells indicating a possible association between MP size and cell‑targeting properties.]]> Tue 03 Sep 2019 18:26:10 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:35745 chromosome 9 open reading frame 3 gene that was transcriptionally activated by p53. Similarly, the host gene of miRNA-455-3p, collagen alpha-1 (XXVII) chain, was also a p53 transcriptional target. Collectively, our results identify miRNA-27b-3p and miRNA-455-3p as important regulators of cancer cell quiescence in response to p53 and suggest that manipulating miRNA-27b-3p and miRNA-455-3p may constitute novel therapeutic avenues for improving outcomes of cancer treatment. Significance: Two novel p53-responsive microRNAs whose distinct mechanisms of action both stabilize p27 to promote cell quiescence and may serve as therapeutic avenues for improving outcomes of cancer treatment.]]> Thu 28 Oct 2021 12:36:09 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:40665 Thu 28 Jul 2022 12:15:19 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45318 Thu 27 Oct 2022 13:56:46 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45314 Thu 27 Oct 2022 13:56:29 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45133 Thu 27 Oct 2022 11:25:41 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:50515 Thu 27 Jul 2023 14:34:40 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:37758 regenerating islet-derived (REG) gene family are important regulators of many cellular processes. Here we functionally characterise a non-protein coding product of the family, the long noncoding RNA (lncRNA) REG1CP that is transcribed from a DNA fragment at the family locus previously thought to be a pseudogene. REG1CP forms an RNA–DNA triplex with a homopurine stretch at the distal promoter of the REG3A gene, through which the DNA helicase FANCJ is tethered to the core promoter of REG3A where it unwinds double stranded DNA and facilitates a permissive state for glucocorticoid receptor α (GRα)-mediated REG3A transcription. As such, REG1CP promotes cancer cell proliferation and tumorigenicity and its upregulation is associated with poor outcome of patients. REG1CP is also transcriptionally inducible by GRα, indicative of feedforward regulation. These results reveal the function and regulation of REG1CP and suggest that REG1CP may constitute a target for cancer treatment.]]> Thu 27 Jan 2022 15:55:02 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:37622 NTR and the proneurotrophin co-receptor sortilin, remains unclear. In the present study, analysis of these proteins was conducted by immunohistochemistry and digital quantification in a series of 204 lung cancers of different histological subtypes versus 121 normal lung tissues. TrkA immunoreactivity was increased in squamous cell carcinoma compared with benign and other malignant lung cancer histological subtypes (p < 0.0001). NGF and proNGF were also increased in squamous cell carcinoma, as well as in adenocarcinoma (p < 0.0001). In contrast, p75^NTR was increased across all lung cancer histological subtypes compared to normal lung (p < 0.0001). Sortilin was higher in adenocarcinoma and small cell carcinoma (p < 0.0001). Nerves in the tumor microenvironment were negative for TrkA, NGF, proNGF, p75^NTR and sortilin. In conclusion, these data suggest a preferential therapeutic value of targeting the NGF-TrkA axis in squamous cell carcinomas of the lung.]]> Thu 24 Mar 2022 11:36:54 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:48496 Thu 24 Aug 2023 13:57:43 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:52635 Thu 19 Oct 2023 15:13:49 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:32504 Thu 14 Apr 2022 10:59:36 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:36692 Thu 13 Jan 2022 10:31:57 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:53744 Thu 11 Jan 2024 12:15:03 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:47931 Thu 09 Feb 2023 12:55:55 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:52226 Thu 05 Oct 2023 10:31:40 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:37125 Thu 03 Feb 2022 12:20:01 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:7349 Sat 24 Mar 2018 08:40:16 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:7006 Sat 24 Mar 2018 08:37:51 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:8335 Sat 24 Mar 2018 08:37:01 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:9621 Sat 24 Mar 2018 08:35:27 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:1955 Sat 24 Mar 2018 08:33:18 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:1051 Sat 24 Mar 2018 08:32:13 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:2788 Sat 24 Mar 2018 08:27:07 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:10609 Sat 24 Mar 2018 08:13:49 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:10654 Sat 24 Mar 2018 08:13:39 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:20838 Sat 24 Mar 2018 08:05:56 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:18969 Sat 24 Mar 2018 07:58:53 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:19564 Sat 24 Mar 2018 07:58:25 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:19159 Sat 24 Mar 2018 07:52:20 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:19310 Sat 24 Mar 2018 07:52:15 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:5563 Sat 24 Mar 2018 07:49:11 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:5319 Sat 24 Mar 2018 07:45:57 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:5398 Sat 24 Mar 2018 07:43:56 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:22827 Sat 24 Mar 2018 07:16:09 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:24678 in vivo and to determine the underlying mechanism by which simvastatin reduces hepatic steatosis.]]> Sat 24 Mar 2018 07:10:52 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:22108 Sat 24 Mar 2018 07:10:20 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:48186 Sat 11 Mar 2023 12:23:00 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:39042 Mon 29 Jan 2024 17:54:16 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:51247 0.2). Nonetheless, the mean expression level of FAT1 was significantly higher in leukemic patients (AML and ALL) than in normal CD34+ cells (p=0.029). Additionally, the FAT1 expression levels were significantly higher in both CD34+ and CD34-leukemic patients than in normal CD34+ cells (p=0.028). Conclusion: No significant differences were found between FAT1 expression in CD34+ and CD34-leukemic samples (p> 0.3). Thus, higher FAT1 expression was evident in ALL and AML leukemia cells but this appeared unrelated to CD34 expression. This suggests in a proportion of adult acute leukemia, FAT1 expression may prove to be a suitable target for therapeutic strategies.]]> Mon 28 Aug 2023 12:28:18 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:49571 Mon 22 May 2023 09:41:08 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:53265 Mon 20 Nov 2023 12:20:50 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:40525 Mon 08 Aug 2022 15:05:19 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:55358 Fri 17 May 2024 16:04:55 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:43403 Fri 16 Sep 2022 10:05:31 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:51723 Fri 15 Sep 2023 17:53:26 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:38689 FAT1 gene was cloned over 20 years ago, but there has only been an incremental understanding of its functional role in cancer and developmental disorders. FAT1 is highly expressed in a large proportion of cases of T-cell acute lymphoblastic leukemia (T-ALL) and B-cell ALL compared to their normal counterparts suggesting an oncogenic function. Conversely, the FAT1 gene is also recurrently mutated in a small subset of TALL cases and also in chronic lymphocytic leukemia. Functionally, the FAT1 cadherin has been implicated in Wnt signaling, hippo signaling and more recently mitochondrial function which together suggests a role outside the classical cadherin function in regulating cell-cell adhesion. Here we show that T-ALL cell lines and clinical samples express a unique N-terminal truncated FAT1 mRNA transcript that generates a protein from a novel transcriptional start site within a retained intronic sequence. This novel transcript is regulated independently of full-length FAT1 and results in the expression of a truncated protein lacking almost the entire extracellular domain of FAT1. Significantly, this truncated protein is a novel biomarker for T-ALL and was found to cooperate with NOTCH in driving T-ALL in vivo, suggesting that in the context of T-ALL, this truncated protein may act as an oncogene.]]> Fri 12 Aug 2022 13:35:10 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:49114 Fri 05 May 2023 11:38:54 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:35545 Fri 03 Dec 2021 10:33:29 AEDT ]]>