https://ogma.newcastle.edu.au/vital/access/ /manager/Index en-au 5 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:53345 Wed 22 Nov 2023 10:19:25 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:48596 Wed 22 Mar 2023 08:46:40 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:50573 30% of patients) of any grade were nausea and musculoskeletal pain. The only dose limiting toxicity (DLT) was diarrhoea in a patient receiving 200 mg NMP (overall DLT rate 8%; 95% CI 0–36%). Hence, the MTD was not defined. Median progression-free and overall survival were 57 (range 29–539) days and 33 (95% CI 9.7– > 44) months, respectively. The best response of stable disease (SD) was achieved in nine patients (69%; 95% CI 39–91%). PK analysis demonstrated proportional dose–concentrations up to 400 mg daily, with a more linear relationship above 500 mg. Maximum plasma concentrations (Cmax) of 16.7 mg/L at the 800 mg dose were below those predicted to inhibit BET-bromodomains. Peripheral blood immune-profiling demonstrated maintenance of natural killer (NK) cells, and a gene expression signature suggestive of enhanced T, B and NK cell functions; a subject with prolonged exposure manifested sustained recovery of B and NK cells at 12 months. Conclusions: NMP demonstrated potential disease stabilising and immunomodulatory activity at sub-BET inhibitory plasma concentrations and was well tolerated in RR–MM; an MTD was not determined up to a maximum dose of 1 g daily. Further dose-finding studies are required to optimise NMP dosing strategies for therapeutic intervention.]]> Wed 15 May 2024 15:53:05 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:33809 -4). We did not find evidence that SNP genotype was influencing the DMR in this cohort. A smaller MHC DMR was also identified at HCG4B, and two non-MHC DMRs at PM20D1 on chr1 and ERICH1 on chr8 were also identified. Conclusions: The findings from this study confirm our previous results of a DMR at HLA-DRB1 and also suggest hypermethylation in an independent MHC locus, RNF39, is associated with MS. Taken together, our results highlight the importance of epigenetic factors at the MHC locus in MS independent of treatment, age and sex. Prospective studies are now required to discern whether methylation at MHC is involved in influencing risk of disease onset or whether the disease itself has altered the methylation profile.]]> Tue 03 Sep 2019 18:30:43 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:52306 Mon 09 Oct 2023 10:16:43 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:52991 Fri 03 Nov 2023 16:05:35 AEDT ]]>