Quantitative phosphoproteomic analysis identifies the potential therapeutic target EphA2 for overcoming sorafenib resistance in hepatocellular carcinoma cells.

Limited therapeutic options are available for advanced-stage hepatocellular carcinoma owing to its poor diagnosis. Drug resistance to sorafenib, the only available targeted agent, is commonly reported. The comprehensive elucidation of the mechanisms underlying sorafenib resistance may thus aid in the development of more efficacious therapeutic agents. To clarify the signaling changes contributing to resistance, we applied quantitative phosphoproteomics to analyze the differential phosphorylation changes between parental and sorafenib-resistant HuH-7 cells. Consequently, an average of ~1500 differential phosphoproteins were identified and quantified, among which 533 were significantly upregulated in resistant cells. Further bioinformatic integration via functional categorization annotation, pathway enrichment and interaction linkage analysis led to the discovery of alterations in pathways associated with cell adhesion and motility, cell survival and cell growth and the identification of a novel target, EphA2, in resistant HuH-7R cells. In vitro functional analysis indicated that the suppression of EphA2 function impairs cell proliferation and motility and, most importantly, overcomes sorafenib resistance. The attenuation of sorafenib resistance may be achieved prior to its development through the modulation of EphA2 and the subsequent inhibition of Akt activity. Binding analyses and in silico modeling revealed a ligand mimic lead compound, prazosin, that could abate the ligand-independent oncogenic activity of EphA2. Finally, data obtained from in vivo animal models verified that the simultaneous inhibition of EphA2 with sorafenib treatment can effectively overcome sorafenib resistance and extend the projected survival of resistant tumor-bearing mice. Thus our findings regarding the targeting of EphA2 may provide an effective approach for overcoming sorafenib resistance and may contribute to the management of advanced hepatocellular carcinoma.

The influence of personality traits and socio-demographic characteristics on paediatric nurses' compassion satisfaction and fatigue.

AIMS: To explore the level of and the association between, compassion satisfaction and fatigue of paediatric nurses; to determine the association between personality traits and compassion satisfaction and fatigue; to identify the determinants of compassion satisfaction and fatigue. BACKGROUND: Paediatric nurses are prone to experiencing compassion fatigue associated with caring for children with illness and their families, yet its connection with nurses' personality traits remains unknown. DESIGN: A cross-sectional descriptive study design was used. METHODS: The data collection used three instruments measuring socio-demography, responses to the compassion satisfaction and fatigue test and the revised NEO personality inventory. The study used descriptive, correlation and multiple regression analysis for the data collected between April - July 2014. RESULTS: From 173 female paediatric nurses, two-thirds worked in critical care units and indicated a satisfactory level of compassion satisfaction and a low level of compassion fatigue, despite a lack of association between the two concepts. Four determinants-agreeableness, extraversion, conscientiousness and engaging with outdoor activities-were predictive and explained 43.6% of total variance of compassion satisfaction. Two risk factors of compassion fatigue identified were less emotional stability and singlehood (marital status) and these explained 26.1% of total variance of compassion fatigue. CONCLUSION: Support for improving agreeableness and emotional stability in paediatric nurses' workplaces including involvement in the outdoor activities and an increase in social connection may enhance compassion satisfaction and prevent exhaustive compassion fatigue.

Main caregivers' experiences of managing pain for children with neuroblastoma in Taiwan.

Neuroblastoma is a common malignant tumor among children. Seventy percent of children with neuroblastoma have metastatic disease when the diagnosis is established. The aim of this study was to understand the main caregivers' lived experiences in managing pain for children with neuroblastoma. A descriptive qualitative design was used. Twelve main caregivers of children with neuroblastoma were interviewed. Two themes evolved: experiences of pain and coping with pain. Three subthemes were found under the theme "experience of pain": pain assessment based on language expressions and behavioral observations, tendency of misdiagnosing tumor metastasis-related pain, and unique manifestations of pain at various phases. Four subthemes evolved under the theme "coping with pain": utilization of pharmacological and nonpharmacological modalities for pain management, learning to confront pain, seeking mental and emotional support, and adjustment of family lifestyle. The results provide a description regarding the expression of pain in children with neuroblastoma and the pain management modalities used by the main caregivers. The findings serve as a reference for health care providers in Taiwan as they manage pain for children with neuroblastoma and seek to understand the needs of the main caregivers.