Our data suggests that the specific downregulation of Mcl-1 by RNAi is a promising approach to induce apoptosis and enhance the chemosensitivity for pancreatic carcinoma gene therapy.

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The currently used vaccine against tuberculosis, Bacille Calmette‐Guérin (BCG), has variable efficacy, so new vaccine development is crucial. In this study, we evaluated a recombinant vaccine prepared from non‐pathogenic Mycobacterium smegmatis (rMS) that expresses a fusion of early secreted antigenic target 6‐kDa antigen (ESAT6) and culture filtrate protein 10 (CFP10). C57BL/6 mice were immunized with the rMS expressing the ESAT6‐CFP10 fusion protein (rM.S‐e6c10) or with BCG. The mice in the rM.S‐e6c10 group had a significantly higher titre of anti‐ESAT6‐CFP10 antibodies than did animals in the BCG or saline groups. Spleen cells from rM.S‐e6c10‐immunized mice exhibited a cytotoxic response to ESAT6 and CFP10‐expressed target cells, but spleen cells from animals in the other groups did not. Levels of IFN‐γ and IL‐2 production by purified T cells from spleens were significantly higher in rM.S‐e6c10 group than in BCG group. Finally, after M. tuberculosis (MTB)‐challenged mice, dramatic reduction in the numbers of MTB colony‐forming units (CFUs) in the lungs was observed for the mice immunized with the rMS. The protective efficacy of rM.S‐e6c10 and BCG vaccination was similar based on measures of MTB burden and lung pathology. Our data indicate that the recombinant M. smegmatis vaccine expressing the ESAT6‐CFP10 fusion protein has potential in clinic application.

Stathmin (Oncoprotein18), a signal transduction regulatory factor, plays an important role in cell division and malignant tumor development. Stathmin is a ubiquitous intracellular phosphoprotein that is overexpressed in a variety of human malignancies, including osteosarcoma. To investigate the potential use of stathmin as a therapeutic target for human osteosarcomas, we employed RNA interference [small interfering RNA (siRNA)] to reduce stathmin expression in human osteosarcoma cell lines and analyzed their phenotypic changes. Results showed that the downregulation of stathmin expression in human osteosarcoma cells significantly inhibited cell proliferation in vitro and tumorigenicity in vivo. The specific downregulation induced cell arrest in the G 2 /M phase of cell cycle and eventually apoptotic cell death. Taxanes are a group of effective chemotherapeutic agents whose activity is mediated through stabilization of the microtubules of the mitotic spindle. In the present study, we also observed a synergistic enhancement of the cytotoxicity effect by combination use of taxanes and RNA interference-mediated stathmin downregulation. All these experimental data indicate that stathmin downregulation can lead to potent antitumor activity and chemosensitizing activity to taxanes in human osteosarcomas.

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