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Now showing items 11-20 of 24
A selective chemical probe for exploring the role of CDK8 and CDK19 in human disease.
(NATURE PUBLISHING GROUP, 2015-12-01)
There is unmet need for chemical tools to explore the role of the Mediator complex in human pathologies ranging from cancer to cardiovascular disease. Here we determine that CCT251545, a small-molecule inhibitor of the WNT ...
Comparative methylome analysis identifies new tumour subtypes and biomarkers for transformation of nephrogenic rests into Wilms tumour
(2015-02-01)
Background: Wilms tumours (WTs) are characterised by several hallmarks that suggest epimutations such as aberrant DNA methylation are involved in tumour progression: loss of imprinting at 11p15, lack of recurrent mutations ...
Multiple mechanisms of MYCN dysregulation in Wilms tumour
(2015-03-01)
Genomic gain of the proto-oncogene transcription factor gene MYCN is associated with poor prognosis in several childhood cancers. Here we present a comprehensive copy number analysis of MYCN in Wilms tumour (WT), demonstrating ...
Restricting direct interaction of CDC37 with HSP90 does not compromise chaperoning of client proteins.
(NATURE PUBLISHING GROUP, 2015-01-02)
The HSP90 molecular chaperone plays a key role in the maturation, stability and activation of its clients, including many oncogenic proteins. Kinases are a substantial and important subset of clients requiring the key ...
Combined MYC and P53 defects emerge at medulloblastoma relapse and define rapidly progressive, therapeutically targetable disease.
(CELL PRESS, 2015-01-12)
We undertook a comprehensive clinical and biological investigation of serial medulloblastoma biopsies obtained at diagnosis and relapse. Combined MYC family amplifications and P53 pathway defects commonly emerged at relapse, ...
Titration of signalling output: insights into clinical combinations of MEK and AKT inhibitors.
(OXFORD UNIV PRESS, 2015-07-01)
BACKGROUND: We aimed to understand the relative contributions of inhibiting MEK and AKT on cell growth to guide combinations of these agents. MATERIALS AND METHODS: A panel of 20 cell lines was exposed to either the MEK ...
First-in-Human Pharmacokinetic and Pharmacodynamic Study of the Dual m-TORC 1/2 Inhibitor AZD2014.
(AMER ASSOC CANCER RESEARCH, 2015-08-01)
PURPOSE: AZD2014 is a novel, oral, m-TORC 1/2 inhibitor that has shown in vitro and in vivo efficacy across a range of preclinical human cancer models. EXPERIMENTAL DESIGN: A rolling six-dose escalation was performed to ...
MOARF, an Integrated Workflow for Multiobjective Optimization: Implementation, Synthesis, and Biological Evaluation.
(AMER CHEMICAL SOC, 2015-06-22)
We describe the development and application of an integrated, multiobjective optimization workflow (MOARF) for directed medicinal chemistry design. This workflow couples a rule-based molecular fragmentation scheme (SynDiR) ...
Neuroblastoma Arginase Activity Creates an Immunosuppressive Microenvironment That Impairs Autologous and Engineered Immunity.
(AMER ASSOC CANCER RESEARCH, 2015-08-01)
Neuroblastoma is the most common extracranial solid tumor of childhood, and survival remains poor for patients with advanced disease. Novel immune therapies are currently in development, but clinical outcomes have not ...
Prognostic role of the LCS6 KRAS variant in locally advanced rectal cancer: results of the EXPERT-C trial.
(OXFORD UNIV PRESS, 2015-09-01)
BACKGROUND: Lethal-7 (let-7) is a tumour suppressor miRNA which acts by down-regulating several oncogenes including KRAS. A single-nucleotide polymorphism (rs61764370, T > G base substitution) in the let-7 complementary ...