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Rabin N.,University College London | Lai M.,Myeloma UK | Pratt G.,Birmingham Hertlands Hospital | Morgan G.,Haemato Oncology | And 9 more authors.
International Journal of Laboratory Hematology | Year: 2014

Therapeutic advances and the availability of novel agents have significantly improved outcomes in myeloma; yet, it remains incurable and strategies to improve survival continue to be sought. One approach is to prolong the duration of response and increase progression-free survival (PFS) through consolidation or maintenance treatment with regimens that have low toxicity profiles, and do not negatively impact on quality of life. Data from several studies with thalidomide, lenalidomide and bortezomib consistently show improvements in response and PFS, although results have still to be confirmed with respect to overall survival (OS). Despite the promising data, the optimal use of consolidation and maintenance treatment in terms of regimen, dose and duration has yet to be defined. Given the evidence to date, the UK Myeloma Forum believes that both maintenance and consolidation therapy should be considered as treatment options for patients with myeloma. Patients should be encouraged to enrol in clinical studies. This document reviews the current position of maintenance and consolidation for patients with myeloma treated in the UK. © 2014 John Wiley & Sons Ltd. Source


Austin C.,Selcia Ltd | Pettit S.N.,Selcia Ltd | Magnolo S.K.,Selcia U.S. Inc | Sanvoisin J.,Selcia Ltd | And 5 more authors.
Journal of Biomolecular Screening | Year: 2012

CEfrag is a new fragment screening technology based on affinity capillary electrophoresis (ACE). Here we report on the development of a mobility shift competition assay using full-length human heat shock protein 90α (Hsp90α), radicicol as the competitor probe ligand, and successful screening of the Selcia fragment library. The CEfrag assay was able to detect weaker affinity (IC50 >500 μM) fragments than were detected by a fluorescence polarization competition assay using FITC-labeled geldanamycin. The binding site of selected fragments was determined by co-crystallization with recombinant Hsp90α N-terminal domain and X-ray analysis. The results of this study confirm that CEfrag is a sensitive microscale technique enabling detection of fragments binding to the biological target in near-physiological solution. © 2012 Society for Laboratory Automation and Screening. Source


Bailey D.,Incisive Media | Carpenter E.P.,Research Building | Coker A.,Center for Amyloidosis and Acute Phase Proteins | Coker S.,Center for Amyloidosis and Acute Phase Proteins | And 13 more authors.
Acta Crystallographica Section D: Biological Crystallography | Year: 2012

The analysis reported here describes detailed structural studies of endothiapepsin (the aspartic proteinase from Endothia parasitica), with and without bound inhibitors, and human pepsin 3b. Comparison of multiple crystal structures of members of the aspartic proteinase family has revealed small but significant differences in domain orientation in different crystal forms. In this paper, it is shown that these differences in domain orientation do not necessarily correlate with the presence or absence of bound inhibitors, but appear to stem at least partly from crystal contacts mediated by sulfate ions. However, since the same inherent flexibility of the structure is observed for other enzymes in this family such as human pepsin, the native structure of which is also reported here, the observed domain movements may well have implications for the mechanism of catalysis. © 2012 International Union of Crystallography Printed in Singapore - all rights reserved. Source

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