Hunter Cancer Research Alliance
As a multidisciplinary and multi-institutional alliance, the Hunter Cancer Research Alliance (HCRA) functions to provide capacity building, funding and strategic support to cancer research across the translational research continuum – from basic research through clinical trials to behavioural, implementation and health services research.
With the support of our partnering institutions, executive leaders and a membership that consists of 250+ cancer-focused researchers, we are working to promote the excellence of cancer research in the Hunter and ultimately improve cancer patient outcomes in our region and beyond.
Journal: Cancer Research
Skp2-Mediated Stabilization of MTH1 Promotes Survival of Melanoma Cells upon Oxidative Stress
Jia Yu Wang, Guang Zhi Liu, James S.Wilmott, Ting La,Yu Chen Feng, Hamed Yari, Xu Guang Yan, Rick F. Thorne, Richard A. Scolyer, Xu Dong Zhang, and Lei Jin
MTH1 helps prevent misincorporation of ROS-damaged dNTPs into genomic DNA; however, there is little understanding of how MTH1 itself is regulated. Here, we report that MTH1 is regulated by polyubiquitination mediated by the E3 ligase Skp2. In melanoma cells, MTH1 was upregulated commonly mainly due to its improved stability caused by K63-linked polyubiquitination. Although Skp2 along with other components of the Skp1-Cullin-F-box (SCF) ubiquitin ligase complex was physically associated with MTH1, blocking the SCF function ablated MTH1 ubiquitination and expression. Conversely, overexpressing Skp2-elevated levels of MTH1 associated with an increase in its K63-linked ubiquitination. In melanoma cell lines and patient specimens, we observed a positive correlation of Skp2 and MTH1 expression. Mechanistic investigations showed that Skp2 limited DNA damage and apoptosis triggered by oxidative stress and that MAPK upregulated Skp2 and MTH1 to render cells more resistant to such stress. Collectively, our findings identify Skp2-mediated K63-linked polyubiquitination as a critical regulatory mechanism responsible for MTH1
upregulation in melanoma, with potential implications to target the MAPK/Skp2/MTH1 pathway to improve its treatment.
Journal: Women and Birth
Wula (Voices) of Aboriginal women on barriers to accepting smoking cessation support during pregnancy: Findings from a qualitative study
M.Bovill, M.Gruppetta, Y.Cadet-James, M.Clarke, B.Bonevski, G.S.Gould
To gather Aboriginal women’s stories of smoking and becoming pregnant to identify the barriers in accepting smoking cessation support during pregnancy.
Qualitative data were collected through use of yarning methodology between August 2015 and January 2016 by an Aboriginal Researcher with experience in social and community services. A short on-line survey was used to collect quantitative data. Interviews only recorded the therapeutic yarning process, which ranged from 9 to 45 min duration, averaging 30 min. Audio-recorded interviews were transcribed and independently coded. A general inductive analysis was used to determine emergent themes.
Twenty Aboriginal women between 17–38 years of age, who were pregnant or recently given birth, living in the Hunter New England (HNE) area took part. Eleven women were still smoking; nine had quit. Most were highly aware of the implications of smoking for their babies. Major themes identified for accepting support were: ambivalence towards a need for support, health professional advice, reduction in smoking, and attitudes to Nicotine Replacement Therapy (NRT). Women reported being advised to cut down, rather than to quit; reducing consumption may be a barrier to accepting NRT. Women recommended enhanced clinical support and Aboriginal community engagement in cessation care.
Aboriginal women in the HNE area reported quitting or reducing their cigarette intake during pregnancy. Health Professionals working with Aboriginal women during pregnancy should give consistent messages to quit smoking completely, and offer increased, ongoing and extensive smoking cessation support to Aboriginal mothers. Clinical practices could partner with Aboriginal communities to support the delivery of smoking cessation services.