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Hypotheses concerning processes and timing of hydrothermal sulfide mineralization in the central Pennsylvanian Appalachians utilize Mississippi Valley-type (MVT) models with Paleozoic ages. To examine this model, we studied sulfide-bearing veins in the Skytop sulfide occurrence that contain pyrite375 °C. The high temperature fluid inclusions occur within 5 feet of the fault. The Re–Os isotope and fluid inclusion data do not fit current models for sulfide generation in central Pennsylvania that invoke MVT hydrothermal processes. These MVT models imply that mineralization in the area formed in the late Paleozoic at relatively low temperatures (120 ± 40 °C) with metals originating from surrounding sedimentary rocks. The data from the present study indicates that a younger, high temperature (>200 °C) mineralization event (represented by the fault breccia pyrite) overprinted the MVT type mineralization (represented by the vein pyrite). The timing of the younger mineralization event coincides with two Cenozoic events in the Appalachian Basin: the Chesapeake Bay impact and Eocene volcanism in the southern portion of the Nittany anticlinorium. [ABSTRACT FROM AUTHOR]

Bortezomib (Velcade, PS341) was licensed in 2003 as a first-in-class 20S proteasome inhibitor indicated for treatment of multiple myeloma, and is currently being evaluated clinically in a range of solid tumours. The mechanisms underlying its cancer cell toxicity are complex. A growing body of evidence suggests proteasome inhibition-dependent regulation of the BCL-2 family is a critical requirement. In particular, the stabilization of BH3-only proteins BIK, NOXA and BIM, appear to be essential for effecting BAX- and BAK-dependent cell death. These mechanisms are reviewed and the implications for favourable novel drug interactions are highlighted.Oncogene (2008) 27, 1189–1197; doi:10.1038/sj.onc.1210744; published online 10 September 2007 [ABSTRACT FROM AUTHOR]

Investigates the expression of immunogenic tumor-associated antigens in malignant mesothelioma cells. Expression of cancer/testis antigens; Role of DNA methylation in the antigen expression; Suitability of cancer/testis antigen-based immunotherapy as an approach to malignant mesothelioma.