• Coping strategies and styles of family carers of persons with enduring mental illness: a mixed methods analysis.

      Kartalova-O'Doherty, Yulia; Doherty, Donna Tedstone; Health Research Board (HRB) (Health Research Board (HRB), 2008-03)
      A qualitative exploratory study investigated the experiences and needs of family carers of persons with enduring mental illness in Ireland. The current mixed-methods secondary study used content analysis and statistical procedures to identify and explore the coping strategies emerging from the original interviews. The majority of family carers reported use of active behavioural coping strategies, sometimes combined with active cognitive or avoidance strategies. The percentage of cares reporting use of active cognitive strategies was the lowest among those whose ill relative lived in their home, and the highest among those whose relative lived independently. Participants with identified active cognitive strategies often reported that their relative was employed or in training. Participants who reported use of avoidance strategies were significantly younger than participants who did not report use of such strategies. The lowest percentage of avoidance strategies was among participants whose ill relative lived independently, whereas the highest was among carers whose relative lived in their home. The findings of this study highlight the importance of a contextual approach to studying coping styles and processes. Further research questions and methodological implications are discussed.
    • Effects of cIAP-1, cIAP-2 and XIAP triple knockdown on prostate cancer cell susceptibility to apoptosis, cell survival and proliferation.

      Gill, Catherine; Dowling, Catherine; O'Neill, Amanda J; Watson, R William G; UCD School of Medicine and Medical Science, University College Dublin, Dublin, Ireland. cgill@hrb.ie (2009)
      BACKGROUND: Manipulating apoptotic resistance represents an important strategy for the treatment of hormone refractory prostate cancer. We hypothesised that the Inhibitor of Apoptosis (IAP) Proteins may be mediating this resistance and knockdown of cIAP-1, cIAP-2 and XIAP would increase sensitivity to apoptosis. METHODS: cIAP-1, cIAP-2 and XIAP where knocked down either individually or in combination using siRNA in androgen independent prostate cancer PC-3 cells as confirmed by real-time PCR and western blotting. Cells were then treated with TRAIL, Etoposide, or Tunicamycin, and apoptosis assessed by PI DNA staining. Apoptosis was confirmed with Annexin V labelling and measurement of PARP cleavage, and was inhibited using the pan-caspase inhibitor, zVAD.fmk. Clonogenic assays and assessment of ID-1 expression by western blotting were used to measure recovery and proliferation. RESULTS: PC-3 are resistant to TRAIL induced apoptosis and have elevated expression of cIAP-1, cIAP-2 and XIAP. Combined knockdown sensitised PC-3 to TRAIL induced apoptosis, but not to Etoposide or Tunicmycin, with corresponding increases in caspase activity and PARP cleavage which was inhibited by ZVAD.fmk. Triple knock down decreased proliferation which was confirmed by decreased ID-1 expression. CONCLUSION: Simultaneous knock down of the IAPs not only sensitised the PC-3 to TRAIL but also inhibited their proliferation rates and clonogenic survival. The inability to alter sensitivity to other triggers of apoptosis suggests that this effect is specific for death receptor pathways and knock down might facilitate immune-surveillance mechanisms to counter cancer progression and, in combination with therapeutic approaches using TRAIL, could represent an important treatment strategy.