This paper focuses on the first phase of research that sought to encourage discussion and to promote a better understanding of the effects of strategic knowledge management (SKM) on innovation and performance in the Portuguese footwear industry. The rationale for the research is based on the understanding that innovation has played a major role in the recent good performance of this industry, building up its global market share and increasing employment and value in the context of Portugal's economic recession. This empirical study, to our knowledge, is the first to examine the interface between SKM, innovation and performance in the footwear industry. The research used a qualitative methodology, gathering data through semi-structured interviews with three chief executive officers of footwear firms and three academic specialists in SKM and innovation. After doing content analysis, we found support for our initial expectation that SKM effects can be inferred whenever shifts in a firm's performance occur as a result of technological and/or organisational innovations. We further propose a model of relationships between SKM, innovation and performance, which will be assessed in a second phase using a quantitative approach.
Less toxic treatment strategies for testicular germ cell tumor (TGCT) patients are needed, as overtreatment is a concern due to the long-term side effects of platin-based chemotherapy. Although clinical benefit from classical hypomethylating agents has to date been limited, TGCTs show an abnormal DNA methylome indicating the potential of treating TGCTs with hypomethylating drugs. We tested, for the first time in TGCT cell lines, a new synthetic flavonoid compound (MLo1302) from the 3-nitroflavanone family of DNA methyltransferase (DNMT) inhibitors. We show that MLo1302 reduces cell viability (including of cisplatin resistant cell line NCCIT-R), with IC50s (inhibitory concentration 50) within the nanomolar range for NCCIT and NTERA-2 cells, and proved its cytotoxic effect. Exposure to MLo1302 reduced DNMT protein expression, similar to decitabine, and showed a partial effect in cell differentiation, reducing protein expression of pluripotency markers. RT2 profiler expression array indicated several dysregulated targets, related to activation of apoptosis, differentiation, and cell cycle arrest. We validated these data by showing increased apoptosis, increased protein expression of cleaved caspase 8 and activated caspase 2, and reduced proliferation (BrdU assay), with increase in CDKN1A and decrease in MIB-1 expression. Therefore, synthetic drugs designed to target DNA methylation in cells may uncover effective treatments for TGCT patients.
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