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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 ...
Intra-tumor genetic heterogeneity and alternative driver genetic alterations in breast cancers with heterogeneous HER2 gene amplification.
(BMC, 2015-05-22)
BACKGROUND: HER2 is overexpressed and amplified in approximately 15% of invasive breast cancers, and is the molecular target and predictive marker of response to anti-HER2 agents. In a subset of these cases, heterogeneous ...
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 ...
Evaluation of diffusion models in breast cancer.
(WILEY, 2015-08-01)
PURPOSE: The purpose of this study is to investigate whether the microvascular pseudodiffusion effects resulting with non-monoexponential behavior are present in breast cancer, taking into account tumor spatial heterogeneity. ...
Many private mutations originate from the first few divisions of a human colorectal adenoma.
(WILEY, 2015-11-01)
Intratumoural mutational heterogeneity (ITH) or the presence of different private mutations in different parts of the same tumour is commonly observed in human tumours. The mechanisms generating such ITH are uncertain. ...
Mouse mammary stem cells express prognostic markers for triple-negative breast cancer.
(BMC, 2015-03-04)
INTRODUCTION: Triple-negative breast cancer (TNBC) is a heterogeneous group of tumours in which chemotherapy, the current mainstay of systemic treatment, is often initially beneficial but with a high risk of relapse and ...
Molecular mechanisms of human IRE1 activation through dimerization and ligand binding.
(IMPACT JOURNALS LLC, 2015-05-30)
IRE1 transduces the unfolded protein response by splicing XBP1 through its C-terminal cytoplasmic kinase-RNase region. IRE1 autophosphorylation is coupled to RNase activity through formation of a back-to-back dimer, although ...
Cyclin-Dependent Kinase Inhibitor AT7519 as a Potential Drug for MYCN-Dependent Neuroblastoma.
(AMER ASSOC CANCER RESEARCH, 2015-11-15)
PURPOSE: MYCN-dependent neuroblastomas have low cure rates with current multimodal treatment regimens and novel therapeutic drugs are therefore urgently needed. In previous preclinical studies, we have shown that targeted ...