https://nova.newcastle.edu.au/vital/access/ /manager/Index en-au 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:15687 Wed 11 Apr 2018 11:09:30 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:21178 BRCA1, EN1, DLEC1, HOXA9, RASSF1A, GATA4, GATA5, HSULF1, CDH1, SFN) were examined and compared in a cohort of 80 primary HGSOC and 12 benign ovarian surface epithelium (OSE) samples using methylation-specific headloop suppression PCR. Results: The genes were variably methylated in primary HGSOC, with HOXA9 methylation observed in 95% of cases. Most genes were rarely methylated in benign OSE, with the exception of SFN which was methylated in all HGSOC and benign OSE samples examined. Methylation of DLEC1 was associated with disease recurrence, independent of tumor stage and suboptimal surgical debulking (HR 3.5 (95% CI:1.10–11.07), p = 0.033). A combination of the methylation status of HOXA9 and EN1 could discriminate HGSOC from benign OSE with a sensitivity of 98.8% and a specificity of 91.7%, which increased to 100% sensitivity with no loss of specificity when pre-operative CA125 levels were also incorporated. Conclusions: This study provides further evidence to support the feasibility of detecting altered DNA methylation patterns as a potential diagnostic and prognostic approach for HGSOC.]]> Sat 24 Mar 2018 07:58:05 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:20038 Sat 24 Mar 2018 07:50:54 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:27522 in vitro and in vivo models. Treatment with HDACi [suberoylanilide hydroxamic acid (SAHA)] and DNMTi [5-AZA-2' deoxycytidine (5-AZA-dc)] decreased cell proliferation in MiaPaCa2 cells, and SAHA treatment, with or without 5-AZA-dc, resulted in higher cell death and lower DNA synthesis compared to 5-AZA-dc alone and controls (DMSO). Further, combination treatment with SAHA and 5-AZA-dc significantly increased expression of p21^WAF1, leading to G1 arrest. Treatment with epigenetic agents delayed tumour growth in vivo, but did not decrease growth of established pancreatic tumours. In conclusion, these data demonstrate a potential role for epigenetic modifier drugs for the management of PC, specifically in the chemoprevention of PC, in combination with other chemotherapeutic agents.]]> Sat 24 Mar 2018 07:28:54 AEDT ]]>