Supporting People With Type 2 Diabetes in the Effective Use of Their Medicine Through Mobile Health Technology Integrated With Clinical Care to Reduce Cardiovascular Risk : Protocol for an Effectiveness and Cost-effectiveness Randomized Controlled Trial

Funding Information: The Support Through Mobile Messaging and Digital Health Technology for Diabetes research team acknowledges the support of the National Institute for Health Research (NIHR) through the Clinical Research Networks. AF, LT, and RR have received support from the NIHR Oxford Biomedical Research Centre. RH received support from the NIHR Collaboration for Leadership in Applied Health Research and Care and North Thames at Bart's Health National Health Service (NHS) Trust. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health. This paper presents independent research funded by the NIHR under its Program Grants for Applied Research as part of a wider program of work (RP-PG-1214-20003). The authors thank the personnel of the University of Oxford Primary Care and Vaccines Clinical Trials Collaborative for providing support in the conduct of the trial.Peer reviewedPublisher PD

Supporting people with type 2 diabetes in effective use of their medicine through mobile health technology integrated with clinical care (SuMMiT-D pilot) : results of a feasibility randomised trial

Funding Information: This publication presents independent research funded by the National Institute for Health and Care Research (NIHR) under its Programme Grants for Applied Research programme (RP-PG-1214–20003). AF and RR are supported by the National Institute for Health and Care Research (NIHR) Oxford Biomedical Research Centre. DPF is supported by the NIHR Manchester Biomedical Research Centre (IS-BRC-1215–20007). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. This research was funded in whole, or in part, by the National Institute for Health and Care Research (NIHR) under its Programme Grants for Applied Research programme (RP-PG-1214–20003). For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. The SuMMiT-D research team acknowledges the support of the Primary Care Clinical Trials Unit and the National Institute for Health and Care Research Clinical Research Network (NIHR CRN). The authors would like to thank the Thames Valley and South Midlands, West Midlands, South West Peninsula and the Greater Manchester Clinical Research Networks and the participating general practices for help with recruitment. The funder had no role in the design, execution, analyses, interpretation of the data, or decision to submit results for this study.Peer reviewe

Abstracts from the NIHR INVOLVE Conference 2017

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Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia

Recurrent chromosomal translocations involving the mixed lineage leukaemia (MLL) gene initiate aggressive forms of leukaemia, which are often refractory to conventional therapies1. Many MLL-fusion partners are members of the super elongation complex (SEC), a critical regulator of transcriptional elongation, suggesting that aberrant control of this process has an important role in leukaemia induction2, 3. Here we use a global proteomic strategy to demonstrate that MLL fusions, as part of SEC2, 3 and the polymerase-associated factor complex (PAFc)4, 5, are associated with the BET family of acetyl-lysine recognizing, chromatin ‘adaptor’ proteins. These data provided the basis for therapeutic intervention in MLL-fusion leukaemia, via the displacement of the BET family of proteins from chromatin. We show that a novel small molecule inhibitor of the BET family, GSK1210151A (I-BET151), has profound efficacy against human and murine MLL-fusion leukaemic cell lines, through the induction of early cell cycle arrest and apoptosis. I-BET151 treatment in two human leukaemia cell lines with different MLL fusions alters the expression of a common set of genes whose function may account for these phenotypic changes. The mode of action of I-BET151 is, at least in part, due to the inhibition of transcription at key genes (BCL2, C-MYC and CDK6) through the displacement of BRD3/4, PAFc and SEC components from chromatin. In vivo studies indicate that I-BET151 has significant therapeutic value, providing survival benefit in two distinct mouse models of murine MLL–AF9 and human MLL–AF4 leukaemia. Finally, the efficacy of I-BET151 against human leukaemia stem cells is demonstrated, providing further evidence of its potent therapeutic potential. These findings establish the displacement of BET proteins from chromatin as a promising epigenetic therapy for these aggressive leukaemias