https://nova.newcastle.edu.au/vital/access/ /manager/Index en-au 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:53913 Wed 28 Feb 2024 15:58:52 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:53342 13,000 adult and pediatric tumor samples across 38 distinct cancer cohorts from The Cancer Genome Atlas and The Therapeutically Applicable Research to Generate Effective Treatments data sets. The differences between canonical miRNAs and the wider miRNAome in terms of expression, clustering, dysregulation, and prognostic standpoint were investigated. The combination of canonical miRNAs and modified miRNAs boosted the quality of clustering results, outlining unique clinicopathologic features among cohorts. Certain modified miRNAs showed opposite expression from their canonical counterparts in cancer, potentially impacting their targets and function. Finally, a shifted and edited miRNA isoform was experimentally validated to directly bind and suppress a unique target. These findings outline the importance of going beyond the well-established paradigm of one mature miRNA per miRNA arm to elucidate novel mechanisms related to cancer progression.]]> Wed 22 Nov 2023 10:18:51 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:30306 Wed 15 Dec 2021 16:09:28 AEDT ]]> https://nova.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://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:17989 Wed 11 Apr 2018 14:22:59 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:6915 Wed 11 Apr 2018 13:15:26 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:5046 Wed 11 Apr 2018 10:25:08 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:29356 Tff1) gene and the tamoxifen-inducible Cre recombinase (CreERT2)–coding sequence. The resulting Tg(Tff1-CreERT2) mice were crossed with mice harboring conditional oncogenic mutations in Kras or Braf. The administration of tamoxifen to the resulting adult Tg(Tff1-CreERT2);Kras^LSL-G12D/+ and Tg(Tff1-CreERT2);Braf^LSL-V600E/+ mice resulted in gastric metaplasia, inflammation, and adenoma development, characterized by excessive STAT3 activity. To assess the contribution of STAT3 to the spontaneously developing gastric adenomas in gp130^F/F mice, which carry a knockin mutation in the Il6 signal transducer (Il6st), we generated Tg(Tff1-CreERT2);Stat3^fl/fl;gp130^F/F mice that also harbor a conditional Stat3 knockout allele and found that tamoxifen administration conferred a significant reduction in their tumor burden. Conversely, excessive Kras activity in Tg(Tff1-CreERT2);Kras^LSL-G12D/+;gp130^F/F mice promoted more extensive gastric inflammation, metaplastic transformation, and tumorigenesis than observed in Tg(Tff1-CreERT2);Kras^LSL-G12D/+ mice. Collectively, our findings demonstrate that advanced gastric tumorigenesis requires oncogenic KRAS or BRAF in concert with aberrant STAT3 activation in epithelial precursor cells of the glandular stomach, providing a new conditional model of gastric cancer in which to investigate candidate therapeutic targets and treatment strategies.]]> Wed 09 Mar 2022 16:03:09 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:32181 Wed 09 Mar 2022 15:58:36 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:48776 Wed 05 Apr 2023 14:02:56 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47842 Wed 01 Feb 2023 16:02:55 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:51303 Thu 31 Aug 2023 14:21:09 AEST ]]> https://nova.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://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:223 Thu 25 Jul 2013 09:09:37 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:33114 Thu 24 Mar 2022 11:29:56 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:48858 Thu 13 Apr 2023 13:29:31 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:51479 Thu 07 Sep 2023 10:53:30 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:7617 10 sunburns ever compared with no sunburns ever). Silicone casts of the dorsum of the hand provide a measure of cumulative UVR dose and number of sunburns over the lifetime, which persists after adjustment for chronological age. They can be used as an objective measure of cumulative past sun exposure in epidemiologic studies, but other determinants of skin damage, such as skin pigmentation, should be concurrently evaluated.]]> Sat 24 Mar 2018 08:34:44 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:1946 Sat 24 Mar 2018 08:33:19 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:1606 Sat 24 Mar 2018 08:30:40 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:999 Sat 24 Mar 2018 08:29:51 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:997 Sat 24 Mar 2018 08:29:48 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:1418 Sat 24 Mar 2018 08:28:14 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:14877 Sat 24 Mar 2018 08:22:24 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:11336 Sat 24 Mar 2018 08:13:29 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:11381 Sat 24 Mar 2018 08:11:51 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:11525 Sat 24 Mar 2018 08:10:22 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:11117 20 months; 5 (63%) remained alive. Clinical benefit rate (overall response + stable disease) was 21% (16 partial responses and 35 stable disease), and median overall survival was 10.0 months. Progression-free survival at 6 months was 15%, and survival was 40.3% at 12 months and 22% at 24 months. Common treatment-related adverse events were generally mild to moderate, and grade 3/4 adverse events included diarrhea (n = 28, 11%), fatigue (n = 6, 2%), and colitis (n = 9, 4%). There were 2 (0.8%) treatment-related deaths. Conclusions: Tremelimumab showed an objective response rate of 6.6%, with all responses being durable ≥170 days since enrollment, suggesting a potential role for tremelimumab in melanoma.]]> Sat 24 Mar 2018 08:09:51 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:11344 Sat 24 Mar 2018 08:08:16 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:10447 Sat 24 Mar 2018 08:08:03 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:17481 Sat 24 Mar 2018 08:04:10 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:17425 Sat 24 Mar 2018 08:01:39 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:19635 Sat 24 Mar 2018 08:01:14 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:21562 Sat 24 Mar 2018 07:59:02 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:20878 Sat 24 Mar 2018 07:57:56 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:20183 Sat 24 Mar 2018 07:51:43 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:5319 Sat 24 Mar 2018 07:45:57 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:27952 T, MTHFR 1298A>C, MTRR 66A>G, MTR 2756A>G, MTR 5049C>A, and CBS 2199 T>C). Maternal folic acid use was ascertained via questionnaire. ORs were estimated using unconditional logistic regression. Case–parent trio analyses were also undertaken. Results: There was weak evidence of a reduced risk of CBT for the MTRR 66GG genotype in the child or father: ORs 0.71 [95% confidence interval (CI), 0.48–1.07]; 0.54 (95% CI, 0.34–0.87), respectively. Maternal prepregnancy folic acid supplementation showed a stronger negative association with CBT risk where the child, mother, or father had the MTRR 66GG genotype (P_interaction = 0.07, 0.10, and 0.18, respectively). Conclusions: Evidence for an association between folate pathway genotypes and CBT is limited in this study. There was possible protection by the MTRR 66GG genotype, particularly when combined with maternal prepregnancy folic acid supplementation; these results are novel and require replication. Impact: The possible interaction between folic acid supplementation and MTRR 66A>G, if confirmed, would strengthen evidence for prepregnancy folate protection against CBT.]]> Sat 24 Mar 2018 07:38:45 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:26954 Sat 24 Mar 2018 07:27:01 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:28919 Sat 24 Mar 2018 07:25:58 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:26915 T, MTHFR 1298A>C, MTRR 66A>G, MTR 2756 A>G, MTR 5049 C>A, CBS 844 Ins68, and CBS 2199 T>C) were genotyped in children and their parents. Information on prepregnancy maternal folic acid supplement use was collected. ORs were estimated with unconditional logistic regression adjusted for frequency-matched variables and potential confounders. Case-parent trios were also analyzed. Results: There was some evidence of a reduced risk of ALL among children who had, or whose father had, the MTRR 66GG genotype: ORs 0.60 [95% confidence interval (CI) 0.39-0.91] and 0.64 (95% CI, 0.40-1.03), respectively. The ORs for paternal MTHFR 677CT and TT genotypes were 1.41 (95% CI, 1.02-1.93) and 1.81 (95% CI, 1.06-3.07). ORs varied little by maternal folic acid supplementation. Conclusions: Some folate pathway gene polymorphisms in the child or a parent may influence ALL risk. While biologically plausible, underlying mechanisms for these associations need further elucidation. Impact: Folate pathway polymorphisms may be related to risk of childhood ALL, but larger studies are needed for conclusive results.]]> Sat 24 Mar 2018 07:23:34 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22830 interaction = 0.004). Estrogen receptor transcript levels showed inverse prediction across the time windows: HR, 0.88 (0.73–1.07) and 1.19 (0.99–1.43), respectively (P_interaction = 0.03). Similar time-, module-, and estrogen-dependent relationships were seen for distant recurrence. Conclusions: Patients with tumors with high estrogen receptor transcript levels benefit most from 5 years' endocrine therapy but show increased recurrence rates after 5 years and may benefit from extended therapy. Improved prognostic profiles may be created by considering period of treatment and follow-up time.]]> Sat 24 Mar 2018 07:16:07 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47275 Mon 27 Mar 2023 13:35:02 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:42806 27-IGF-II inhibits IGF-I:IGFBP:VN-stimulated breast cancer cell migration and proliferation in two- and three-dimensional assay systems. Peptide arrays screened to identify regions critical for the IGFBP-3/-5:VN and IGF-II:VN interactions demonstrated IGFBP-3/-5 and IGF-II binds VN through the hemopexin-2 domain, and VN binds IGFBP-3 at residues not involved in the binding of IGF-I to IGFBP-3. IGFBP-interacting VN peptides identified from these peptide arrays disrupted the IGF-I:IGFBP:VN complex, impeded the growth of primary tumor-like spheroids and, more importantly, inhibited the invasion of metastatic breast cancer cells in 3D assay systems. These studies provide first-in-field evidence for the utility of small peptides in antagonizing GF:ECM-mediated biologic functions and present data demonstrating the potential of these peptide antagonists as novel therapeutics.]]> Mon 05 Sep 2022 09:43:19 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:53140 Fri 17 Nov 2023 11:42:18 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:55358 Fri 17 May 2024 16:04:55 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:28221 Fri 16 Oct 2020 16:09:46 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47283 Fri 13 Jan 2023 10:24:53 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:49407 Fri 12 May 2023 14:55:16 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:51515 Fri 08 Sep 2023 12:04:15 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:55248 Fri 03 May 2024 09:04:54 AEST ]]>