摘要：Objective: The incidence and mortality rates for cutaneous melanoma (CM) have increased markedly in the last few years. As such, the aim of this study was to forecast their progression in Spain up until 2022. Design: A prospective epidemiological study using the Miamod technique. The primary data source was the mortality statistics released by the National Statistics Institute. Study selection: The MIAMOD method was used. Data extraction: Cases of death due to general and melanoma-related mortality in Spain between 1998 and 2007. Results: In men, the incidence is expected to increase from 11.85 (adjusted: 8.52) to 14.79 (adjusted: 9.43) per 100,000 inhabitants over the period 1998-2022. Similarly, the mortality is expected to increase slightly from 5.84 (adjusted: 4.12) to 7.19 (adjusted: 4.49) per 100,000 inhabitants, and the prevalence from 73.72 (adjusted: 52.31) to 95.46 (adjusted: 60.02) per 100,000 inhabitants over the same period. In women, the incidence is expected to increase from 3.79 (adjusted: 3.04) to 6.46 (adjusted: 4.21) per 100,000 inhabitants between 1998 and 2022, although this increase is not statistically significant. The mortality is expected to increase from 1.67 (adjusted: 1.24) to 2.98 (adjusted: 1.86) per 100,000 inhabitants, and the prevalence from 50.04 (adjusted: 44.54) to 84.81 per (adjusted: 56.18) 100,000 inhabitants over the same period. Conclusions: Primary and secondary prevention programs for this disease must be maintained.

摘要：The differential distribution between cancer cells and normal adult tissues makes survivin a very attractive cancer drug target. We have previously reported a series of novel selective survivin inhibitors with the most potent compound MX 106 reaching nanomolar activity in several cancer cell lines. Further optimization of the MX 106 scaffold leads to the discovery of more potent and more selective survivin inhibitors. Various structural modifications were synthesized and their anticancer activities were evaluated to determine the structure activity relationships for this MX 106 scaffold. In vitro anti-proliferative assays using two human melanoma cell lines showed that several new analogs have improved potency compared to MX 106. Very interestingly, these new analogs generally showed significantly higher potency against P-glycoprotein overexpressed cells compared with the corresponding parental cells, suggesting that these compounds may strongly sensitize tumors that have high expressions of the Pglycoprotein drug efflux pumps. Western blotting analysis confirmed that the new MX 106 analogs maintained their mechanism of actions by selectively suppressing survivin expression level among major inhibitors of apoptotic proteins and induced strong apoptosis in melanoma tumor cells.