Gareth Morgan

..These combined approaches will hopefully transform the current one-for-all care into a more tailored, individual therapeutic strategy for MM patients...

..02) and also from first on-study disease progression (median, 34 months for ZOL vs 27 months for CLO; P = .03). Thalidomide-containing regimens had better efficacy than traditional regimens, and ZOL demonstrated greater benefits than CLO...

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..While these supportive care options are directed towards improving patient quality of life, they also have significant effect against the disease and can improve survival...

..Thalidomide is active in multiple myeloma and is associated with minimal myelosuppression, making it a good candidate for induction therapy prior to high-dose therapy with autologous stem-cell transplantation...

..Overview analysis demonstrated that thalidomide maintenance was associated with a significant late OS benefit. This trial was registered at www.isrctn.org as #ISRCTN68454111...

..Unravelling the mechanisms underlying myeloma-bone interactions will facilitate the development of novel therapeutic agents to treat BD, which as a consequence are likely to improve the clinical outcome of myeloma patients...

..To explore SNP associations with PFS we compared SNP profiles of short term (less than 1 year, n = 70) versus long term progression-free survivors (greater than 3 years, n = 73) in two phase III clinical trials...

..To indentify genetic variation that can modulate and predict the risk of developing thalidomide-related peripheral neuropathy (TrPN)...

..We aimed to establish whether bisphosphonates can affect clinical outcomes in patients with multiple myeloma...

..The MRC Myeloma IX study was designed to compare the effects of zoledronic acid versus clodronic acid in newly diagnosed patients with multiple myeloma. Here, we report the secondary outcomes relating to skeletal events...

..g. induction, salvage, or maintenance) in which they may provide the greatest impact on the disease course...

..We highlight the importance of cytogenetic profiling at diagnosis and effective management of adverse events. This trial was registered at International Standard Randomized Controlled Trials Number as #68454111...

..Further analyses of these data will provide greater insight into ZOL interactions with primary treatment regimens for multiple myeloma...

..0001). These data suggest that the sequence of therapy employed is active in AML, but additional steps are needed to improve the outcome of patients with intermediate- and high-risk cytogenetic abnormalities...

..In this review, we discuss the benefits of SNP-based arrays along with some of the drawbacks and how that data can be used in conjunction with expression data to identify genes with altered expression in regions of interest...

..Using this strategy, of a single prior course of chemotherapy followed by immediate harvest, it is feasible to offer early high-dose therapy in clinical situations where this is important...

..This review assesses the current body of preclinical and clinical evidence in favor of an antitumor effect of bisphosphonates in different cancer types...

..This study highlights the importance of XBP1 in myeloma and its significance as an independent prognostic marker and as a predictor of thalidomide response...

..These findings suggest that non-cycling cells in AML may constitute a disease reservoir that is resistant to TK inhibition. Further studies with a larger sample size and other inhibitors are warranted...

..This study was registered at http://isrctn.org as ISRCTN68454111...

..Overall, DNA methylation changes significantly during disease progression and between cytogenetic subgroups...

..We have documented these genes, providing a focus for further studies to identify and characterize those that are key in the pathogenesis of myeloma...

..The incidence of acquired mutations in AML patients with acute megakaryoblastic leukemia (FAB type M7) was the same as that reported in other non-M0 patients, with only one mutation detected in 20 (5%) patients studied...

..Here, we review the rationale for identifying genetic risk variants for MM and our proposed strategy for establishing MAGIC...

..In conclusion, the clinical outcome of this group of cases is poor even when treated with the intensive regimen DT-PACE; however, a subgroup can do well if DT-PACE is consolidated by ASCT...

..However, these indicators do not capture all prognostic information. Gene expression analysis can be used to identify poor-prognosis patients and this can be improved by combination with information about DNA-level changes...

..These 2 genes and their corresponding pathways provide an important insight into the potential mechanisms by which 16q LOH confers poor prognosis...

..We propose a multiparametric risk-adapted model that includes response to induction chemotherapy and HDM, for identifying patients who may benefit from novel approaches to treatment...

..This represents a challenge for both drug development and clinical trial evaluation, which has the potential to revolutionise the clinical management of myeloma and a paradigm for drug development in other diseases...

..02). In particular, amplification of 2p and deletion of 6q were both more frequent. Cases with >20%TP53-deleted cells had the worst prognosis in the LRF CLL4 trial...

..Lenalidomide, cyclophosphamide and dexamethasone is a safe, effective combination in relapsed myeloma inducing a high response rate, warranting further investigation in phase III trials...

..60%, P = 0.0002) with CVAMP and more thrombotic episodes with CTD (11% vs. 4%). CTD may emerge as the superior induction regimen prior to PBSCT, in terms of high efficacy and better tolerability...

..The role of proteasome inhibitors in the management of myeloma is also discussed...

..Herein, we review the data currently available on both Ig gene rearrangements and protein patterns seen in myeloma with the aim of illustrating how this knowledge has contributed to our understanding of the pathobiology of myeloma...

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..The involvement of MMSET in the pathogenesis of t(4;14) multiple myeloma and the mechanism or genes deregulated by MMSET upregulation are still unclear...

..57; 95% confidence interval, 0.38-0.86. The results of this study did not support our starting hypothesis; that high producer haplotypes at the TNF locus are associated with an increased risk of developing myeloma...

..The clinical trials described in this paper have been registered as follows: MRC Myeloma IX: ISRCTN68454111; Hovon-50: NCT00028886; and ECOG EA100: NCT00033332...

..3 has been identified in myeloma cell lines as the potential target of the deletion. We tested the clinical impact of 1p deletion and used high-resolution techniques to define the role of CDKN2C in primary patient material...

..Several cancer types have differences in incidence and clinical outcome dependent on gender, but these are not well described in myeloma. The aim of this study was to characterize gender disparities in myeloma...

..This reinforces the need for long-term follow-up of all patients exposed to chemoradiotherapy and confirms that chemotherapeutic agents can cause lymphoma...

..All drugs inhibited proliferation and induced cell death with activation of JNK and caspase cleavage. In conclusion, Hsp90 inhibitors induce myeloma cell death at least in part via endoplasmic reticulum stress and the UPR death pathway...

..These studies demonstrate that reversible SLO permeabilisation can successfully be applied to hard-to-transfect human myeloma cell lines to effectively silence genes...

..In this article, based on work in multiple myeloma, we highlight the importance of targeting multiple signalling pathways simultaneously, using the UPR and heat shock proteins as examples, as a means of effectively killing cancer cells...

..In conclusion, inhibiting protein turnover using the aminopeptidase inhibitor CHR-2797 results in myeloma cell apoptosis and represents a novel therapeutic approach that warrants further investigation in the clinical setting...