59 research outputs found

    Clinical and laboratory experience of vorinostat (suberoylanilide hydroxamic acid) in the treatment of cutaneous T-cell lymphoma

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    The most common cutaneous T-cell lymphomas (CTCLs) – mycosis fungoides (MF) and Sézary Syndrome – are characterised by the presence of clonally expanded, skin-homing helper-memory T cells exhibiting abnormal apoptotic control mechanisms. Epigenetic modulation of genes that induce apoptosis and differentiation of malignant T cells may therefore represent an attractive new strategy for targeted therapy for T-cell lymphomas. In vitro studies show that vorinostat (suberoylanilide hydroxamic acid or SAHA), an oral inhibitor of class I and II histone deacetylases, induces selective apoptosis of malignant CTCL cell lines and peripheral blood lymphocytes from CTCL patients at clinically achievable doses. In a Phase IIa clinical trial, vorinostat therapy achieved a meaningful partial response (>50% reduction in disease burden) in eight out of 33 (24%) patients with heavily pretreated, advanced refractory CTCL. The most common major toxicities of oral vorinostat therapy were fatigue and gastrointestinal symptoms (diarrhoea, altered taste, nausea, and dehydration from not eating). Thrombocytopenia was dose limiting in patients receiving oral vorinostat at the higher dose induction levels of 300 mg twice daily for 14 days. These studies suggest that vorinostat represents a promising new agent in the treatment of CTCL patients. Additional studies are underway to define the exact mechanism (s) of by which vorinostat induces selective apoptosis in CTCL cells and to further evaluate the antitumour efficacy of vorinostat in a Phase IIb study in CTCL patients

    The Space Physics Environment Data Analysis System (SPEDAS)

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    With the advent of the Heliophysics/Geospace System Observatory (H/GSO), a complement of multi-spacecraft missions and ground-based observatories to study the space environment, data retrieval, analysis, and visualization of space physics data can be daunting. The Space Physics Environment Data Analysis System (SPEDAS), a grass-roots software development platform (www.spedas.org), is now officially supported by NASA Heliophysics as part of its data environment infrastructure. It serves more than a dozen space missions and ground observatories and can integrate the full complement of past and upcoming space physics missions with minimal resources, following clear, simple, and well-proven guidelines. Free, modular and configurable to the needs of individual missions, it works in both command-line (ideal for experienced users) and Graphical User Interface (GUI) mode (reducing the learning curve for first-time users). Both options have “crib-sheets,” user-command sequences in ASCII format that can facilitate record-and-repeat actions, especially for complex operations and plotting. Crib-sheets enhance scientific interactions, as users can move rapidly and accurately from exchanges of technical information on data processing to efficient discussions regarding data interpretation and science. SPEDAS can readily query and ingest all International Solar Terrestrial Physics (ISTP)-compatible products from the Space Physics Data Facility (SPDF), enabling access to a vast collection of historic and current mission data. The planned incorporation of Heliophysics Application Programmer’s Interface (HAPI) standards will facilitate data ingestion from distributed datasets that adhere to these standards. Although SPEDAS is currently Interactive Data Language (IDL)-based (and interfaces to Java-based tools such as Autoplot), efforts are under-way to expand it further to work with python (first as an interface tool and potentially even receiving an under-the-hood replacement). We review the SPEDAS development history, goals, and current implementation. We explain its “modes of use” with examples geared for users and outline its technical implementation and requirements with software developers in mind. We also describe SPEDAS personnel and software management, interfaces with other organizations, resources and support structure available to the community, and future development plans
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