• The Eag potassium channel as a new prognostic marker in ovarian cancer.

      Asher, Viren; Khan, Raheela; Warren, Averil; Shaw, Robert; Schalkwyk, Gerhard V.; Bali, Anish; Sowter, Heidi M.; Royal Derby Hospital, School of Graduate Entry Medicine and Health, Department of Obstetrics and Gynaecology; University of Derby (2010)
      Ovarian cancer is the second most common cancer of the female genital tract in the United Kingdom (UK), accounting for 6% of female deaths due to cancer. This cancer is associated with poor survival and there is a need for new treatments in addition to existing chemotherapy to improve survival. Potassium (K+) channels have been shown to be overexpressed in various cancers where they appear to play a role in cell proliferation and progression.
    • Identification of novel candidate biomarkers of epithelial ovarian cancer by profiling the Secretomes of three-dimensional genetic models of ovarian carcinogenesis.

      Lawrenson, Kate; Mhawech-Fauceglia, Paulette; Worthington, Jenny; Spindler, Tassja J.; O'Brien, Darragh; Lee, Janet M.; Spain, Georgia; Sharifian, Maryam; Wang, Guisong; Darcy, Kathleen M.; et al. (Wiley, 2014-09-09)
      Epithelial ovarian cancer is still considered the most lethal gynecological malignancy and improved early detection of ovarian cancer is crucial to improving patient prognoses. To address this need, we tested whether candidate EOC biomarkers can be identified using three-dimensional in vitro models. We quantified changes in the abundance of secreted proteins in a 3D genetic model of early-stage EOC, generated by expressing CMYC and KRAS(G12V) in TERT-immortalized normal ovarian epithelial cells. Cellular proteins were labeled in live cells using stable isotopic amino acid analogues, and secreted proteins identified and quantified using liquid chromatography-tandem mass spectrometry. 37 and 55 proteins were differentially expressed by CMYC and CMYC+KRAS(G12V) expressing cells respectively (P<0.05; >2-fold). We evaluated expression of the top candidate biomarkers in ˜210 primary EOCs: CHI3L1 and FKBP4 are both expressed by >96% of primary EOCs, and FASN and API5 are expressed by 86% and 75% of cases. High expression of CHI3L1 and FKBP4 was associated with worse patient survival (P=0.042 and P=0.002 respectively). Expression of LGALS3BP was positively associated with recurrence (P=0.0001) and suboptimal debulking (P=0.018) suggesting that these proteins may be novel prognostic biomarkers. Furthermore, within early stage tumours (I/II), high expression of API5, CHI3L1 and FASN was associated with high tumour grade (P=3x10(-4) , P=0.016, P=0.010, respectively). We show in vitro cell biology models of early-stage cancer development can be used to identify novel candidate biomarkers for disease, and report the identification of proteins that represent novel potential candidate diagnostic and prognostic biomarkers for this highly lethal disease. © 2014 Wiley Periodicals, Inc.
    • The role of Eag and HERG channels in cell proliferation and apoptotic cell death in SK-OV-3 ovarian cancer cell line.

      Asher, Viren; Warren, Averil; Shaw, Robert; Sowter, Heidi M.; Bali, Anish; Khan, Raheela; Royal Derby Hospital, School of Graduate Entry Medicine and Health; University of Derby, Faculty of Education, Health and Science (2011-03)
      The voltage gated potassium (K+) channels Eag and HERG have been implicated in the pathogenesis of various cancers, through association with cell cycle changes and programmed cell death. The role of these channels in the onset and progression of ovarian cancer is unknown. An understanding of mechanism by which Eag and HERG channels affect cell proliferation in ovarian cancer cells is required and therefore we investigated their role in cell proliferation and their effect on the cell cycle and apoptosis of ovarian cancer cells.