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Inhibition of the proteasome offers many therapeutic possibilities in inflammation as well as in neoplastic diseases. However, clinical use of proteasome inhibitors is limited by the development of resistance or severe side effects. In our study we characterized the anti-tumor properties of the novel proteasome inhibitor BSc2118. The sensitivity of tumor lines to BSc2118 was analyzed in comparison to bortezomib using crystal violet staining in order to assess cell viability. The In Vivo distribution of BSc2118 in mouse tissues was tracked by a fluorescent-modified form of BSc2118 (BSc2118-FL) and visualized by confocal microscopy. Inhibition of the 20S proteasome was monitored both in cultured cell lines and in mice, respectively. Finally, safety and efficacy of BSc2118 was evaluated in a mouse melanoma model. BSc2118 inhibits proliferation of different tumor cell lines with a similar potency as compared with bortezomib. Systemic administration of BSc2118 in mice is well tolerated, even when given in a dose of 60 mg/kg body weight. After systemic injection of BSc2118 or bortezomib similar proteasome inhibition patterns are observed within the murine organs. Detection of BSc2118-FL revealed correlation of distribution pattern of BSc2118 with inhibition of proteasomal activity in cells or mouse tissues. Finally, administration of BSc2118 in a mouse melanoma model shows significant local anti-tumor effects. Concluding, BSc2118 represents a novel low-toxic agent that might be alternatively used for known proteasome inhibitors in anti-cancer treatment.

Military global influenza surveillance began in 1976 as an Air Force program. In 1997, the Department of Defense (DoD) Global Emerging Infections Surveillance and Response System expanded the program to include all services. Also included were local residents in areas where DoD overseas research activities operated. This new, worldwide DoD surveillance infrastructure provides valuable information and can respond quickly to outbreaks. This was demonstrated during the current influenza season when a suspected outbreak was reported in Panama. In less than 3 weeks, specimens were collected, transported, and cultured, and isolates were subtyped and sent to the Centers for Disease Control and Prevention for further studies. This influenza surveillance initiative combines viral isolation, antigenic characterization, and molecular sequencing with clinical and public health management of information. The information obtained is shared with the Centers for Disease Control and Prevention and the World Health Organization and has contributed to important decisions in influenza vaccine composition.