https://nova.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://nova.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://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:15135 Wed 11 Apr 2018 16:07:24 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:40073 Thu 14 Jul 2022 13:32:13 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:33182 Thu 13 Jan 2022 10:31:51 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:8242 Sat 24 Mar 2018 08:40:41 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:11060 Sat 24 Mar 2018 08:10:37 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22116 Streptococcus pneumoniae (Spn). The effect of Spn IMT on the development of asthma [allergic airways disease (AAD)] was determined in mice. Killed Spn was administered before, during or after ovalbumin sensitization, and the subsequent development of AAD was assessed. IMT attenuated T cell cytokine production, goblet cell hyperplasia, airways hyperresponsiveness (AHR), and eosinophil numbers in the blood, bronchoalveolar lavage fluid and peribronchial tissue. This indicates the potential of Spn as an IMT for asthma.]]> Sat 24 Mar 2018 07:13:18 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:42843 n = 195; untreated n = 338). Median on-study pairwise-censored follow-up was 3.4 years (quartiles 1.2–5.5). No difference in the hazard of experiencing 3-month confirmed EDSS progression events was observed between the groups [hazard ratio (HR), 1.0; 95% confidence interval (CI), 0.6–1.7, P = 0.87]. We did not find significant differences in the hazards of confirmed EDSS improvement (HR, 1.0; 95% CI, 0.6–1.6, P = 0.91) or reaching a confirmed EDSS step ≥7 (HR, 1.1; 95% CI, 0.7–1.6, P = 0.69). Conclusion: Our pooled analysis of disease-modifying agents suggests that these therapies have no substantial effect on short- to medium-term disability outcomes in PPMS.]]> Mon 05 Sep 2022 14:44:21 AEST ]]>