ABSTRACT
The development of new anticancer drugs is necessary in order deal with the disease and with the drawbacks of currently applied drugs. Epigenetic dysregulations are a central hallmark of cancerogenesis and histone deacetylases (HDACs) emerged as promising anticancer targets. HDAC inhibitors are promising epigenetic anticancer drugs and new HDAC inhibitors are sought for in order to obtain potent drug candidates. The new HDAC inhibitor SF5-SAHA was synthesized and analyzed for its anticancer properties. The new compound SF5-SAHA showed strong inhibition of tumor cell growth with IC50 values similar to or lower than that of the clinically applied reference compound vorinostat/SAHA (suberoylanilide hydroxamic acid). Target specific HDAC inhibition was demonstrated by Western blot analyses. Unspecific cytotoxic effects were not observed in LDH-release measurements. Pro-apoptotic formation of reactive oxygen species (ROS) and caspase-3 activity induction in prostate carcinoma and hepatocellular carcinoma cell lines DU145 and Hep-G2 seem to be further aspects of the mode of action. Antiangiogenic activity of SF5-SAHA was observed on chorioallantoic membranes of fertilized chicken eggs (CAM assay). The presence of the pentafluorothio-substituent of SF5-SAHA increased the antiproliferative effects in both solid tumor and leukemia/lymphoma cell models when compared with its parent compound vorinostat. Based on this preliminary study, SF5-SAHA has the prerequisites to be further developed as a new HDAC inhibitory anticancer drug candidate.
ABSTRACT
BACKGROUND: Given the fact of an aging society, new supply measures and living concepts are needed, especially as health impairments along with care dependency increase with age. As many elderly people wish to stay at home for as long as possible, ambient assisted living (AAL) represents a support for aging in place. OBJECTIVE: AAL combines medical and care technology within living environments and is, therefore, a promising approach to cope with demographic change in terms of fast-growing care needs and fewer skilled workers. Ultrasonic whistles represent one innovative technical possibility for such supportive housing solutions. Central fields of application are home automation, emergency service, and positioning. As AAL technologies affect sensitive areas of life, it is of great interest under which conditions they are accepted or rejected, taking individual user requirements into account. Hence, the aim of this study was to investigate users' perception and evaluation of ultrasonic whistles. METHODS: In this study, we examined the acceptance of ultrasonic whistles in home care by function and room using a Web-based questionnaire. Besides an evaluation of the overall usefulness, we focused on the intention to use ultrasonic whistles; 270 participants assessed home automation, emergency service, and positioning as specific functions of ultrasonic whistles. Furthermore, bathroom, bedroom, and living room were evaluated as specific usage locations (rooms). With regard to the user's perspective, the focus was set on age and attitudes toward aging of care receivers. RESULTS: This study revealed a significant influence of function (F2,269=60.444; P<.001), room (F2,269=41.388; P<.001), and the interaction of function and room (F4,269=8.701; P<.001) on the acceptance of ultrasonic whistles. The use of emergency services within the bathroom represented the most accepted alternative, whereas positioning within the living room received the comparably lowest evaluations. Although user diversity played a minor role for acceptance overall, the assessment of single applications differed among user groups, particularly with regard to age differences (F20,500=1.988; P<.01) in the evaluation of specific installation options such as automated doors. CONCLUSIONS: The study revealed profound insights into the user-centered assessment of ultrasonic whistles in home care and discovered function and room as influencing acceptance parameters. Concerning user characteristics, age, and attitude toward aging partly affected these evaluations, forming the basis for and showing the importance of further investigations in this context.
