Recent submissions
Now showing items 601-620 of 658
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Impact of fusion gene status versus histology on risk-stratification for rhabdomyosarcoma: Retrospective analyses of patients on UK trials.
(WILEY, 2017-07-01)BACKGROUND: Long-term toxicities from current treatments are a major issue in paediatric cancer. Previous studies, including our own, have shown prognostic value for the presence of PAX3/7-FOXO1 fusion genes in rhabdomyosarcoma ... -
MicroRNA and gene co-expression networks characterize biological and clinical behavior of rhabdomyosarcomas.
(ELSEVIER IRELAND LTD, 2017-01-28)Rhabdomyosarcomas (RMS) in children and adolescents are heterogeneous sarcomas broadly defined by skeletal muscle features and the presence/absence of PAX3/7-FOXO1 fusion genes. MicroRNAs are small non-coding RNAs that ... -
Recurrent MET fusion genes represent a drug target in pediatric glioblastoma.
(NATURE PORTFOLIO, 2016-11-01)Pediatric glioblastoma is one of the most common and most deadly brain tumors in childhood. Using an integrative genetic analysis of 53 pediatric glioblastomas and five in vitro model systems, we identified previously ... -
Pre-clinical quantitative imaging and mouse-specific dosimetry for 111In-labelled radiotracers.
(SPRINGER HEIDELBERG, 2016-11-25)BACKGROUND: Accurate quantification in molecular imaging is essential to improve the assessment of novel drugs and compare the radiobiological effects of therapeutic agents prior to in-human studies. The aim of this study ... -
Combining Molecularly Targeted Agents: Is More Always Better?
(AMER ASSOC CANCER RESEARCH, 2017-03-01)The concurrent targeting of critical nodes along key signaling pathways with molecularly targeted agents is a rational antitumor strategy, which has had varying degrees of success. Combinatorial challenges include overcoming ... -
Synthesis of trisubstituted pyrimidines by regioselective S<sub>N</sub>Ar and Suzuki reactions of polyhalopyrimidines
(GEORG THIEME VERLAG KG, 2006-04-04)An efficient, regioselective approach to the synthesis of trisubstituted pyrimidines was developed. Sequential functionalization of com. available polyhalopyrimidines provided the target compds. in moderate to good overall ... -
Discovery of a Chemical Probe Bisamide (CCT251236): An Orally Bioavailable Efficacious Pirin Ligand from a Heat Shock Transcription Factor 1 (HSF1) Phenotypic Screen.
(AMER CHEMICAL SOC, 2017-01-12)Phenotypic screens, which focus on measuring and quantifying discrete cellular changes rather than affinity for individual recombinant proteins, have recently attracted renewed interest as an efficient strategy for drug ... -
Inhibition of mTOR-kinase destabilizes MYCN and is a potential therapy for MYCN-dependent tumors.
(IMPACT JOURNALS LLC, 2016-09-06)MYC oncoproteins deliver a potent oncogenic stimulus in several human cancers, making them major targets for drug development, but efforts to deliver clinically practical therapeutics have not yet been realized. In childhood ... -
The ALK inhibitor PF-06463922 is effective as a single agent in neuroblastoma driven by expression of ALK and MYCN.
(COMPANY BIOLOGISTS LTD, 2016-09-01)The first-in-class inhibitor of ALK, c-MET and ROS1, crizotinib (Xalkori), has shown remarkable clinical efficacy in treatment of ALK-positive non-small cell lung cancer. However, in neuroblastoma, activating mutations in ... -
Minimizing bias in target selection by exploiting multidisciplinary Big Data and the protein interactome.
(FUTURE SCI LTD, 2016-09-01) -
Plasma Metabolomic Changes following PI3K Inhibition as Pharmacodynamic Biomarkers: Preclinical Discovery to Phase I Trial Evaluation.
(AMER ASSOC CANCER RESEARCH, 2016-06-01)PI3K plays a key role in cellular metabolism and cancer. Using a mass spectrometry-based metabolomics platform, we discovered that plasma concentrations of 26 metabolites, including amino acids, acylcarnitines, and ... -
Exploiting Protein Conformational Change to Optimize Adenosine-Derived Inhibitors of HSP70.
(AMER CHEMICAL SOC, 2016-05-26)HSP70 is a molecular chaperone and a key component of the heat-shock response. Because of its proposed importance in oncology, this protein has become a popular target for drug discovery, efforts which have as yet brought ... -
PIM1 kinase regulates cell death, tumor growth and chemotherapy response in triple-negative breast cancer.
(NATURE PUBLISHING GROUP, 2016-11-01)Triple-negative breast cancers (TNBCs) have poor prognosis and lack targeted therapies. Here we identified increased copy number and expression of the PIM1 proto-oncogene in genomic data sets of patients with TNBC. TNBC ... -
Antibody-drug conjugates--an emerging class of cancer treatment.
(NATURE PUBLISHING GROUP, 2016-02-16)Antibody-drug conjugates (ADCs) are an emerging novel class of anticancer treatment agents that combines the selectivity of targeted treatment with the cytotoxic potency of chemotherapy drugs. New linker technology associated ... -
Hyperglycemia and Phosphatidylinositol 3-Kinase/Protein Kinase B/Mammalian Target of Rapamycin (PI3K/AKT/mTOR) Inhibitors in Phase I Trials: Incidence, Predictive Factors, and Management.
(ALPHAMED PRESS, 2016-07-01)BACKGROUND: Dysregulation of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway is implicated in human cancer growth and progression. Agents targeting this pathway are ... -
Structure-Based Optimization of Potent, Selective, and Orally Bioavailable CDK8 Inhibitors Discovered by High-Throughput Screening.
(AMER CHEMICAL SOC, 2016-10-27)The mediator complex-associated cyclin dependent kinase CDK8 regulates β-catenin-dependent transcription following activation of WNT signaling. Multiple lines of evidence suggest CDK8 may act as an oncogene in the development ... -
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 ... -
Complications of hyperglycaemia with PI3K-AKT-mTOR inhibitors in patients with advanced solid tumours on Phase I clinical trials.
(NATURE PUBLISHING GROUP, 2015-12-01)BACKGROUND: PI3K-AKT-mTOR inhibitors (PAMi) are promising anticancer treatments. Hyperglycaemia is a mechanism-based toxicity of these agents and is becoming increasingly important with their use in larger numbers of ... -
Noncoding RNAs as novel biomarkers in pancreatic cancer: what do we know?
(FUTURE MEDICINE LTD, 2017-02-01)Pancreatic cancer is an aggressive cancer of the digestive system, which is becoming a serious health problem worldwide. Overall survival for patients with pancreatic cancer is poor, mainly due to a lack of biomarkers to ... -
The genomic landscape of testicular germ cell tumours: from susceptibility to treatment.
(NATURE PUBLISHING GROUP, 2016-07-01)The genomic landscape of testicular germ cell tumour (TGCT) can be summarized using four overarching hypotheses. Firstly, TGCT risk is dominated by inherited genetic factors, which determine nearly half of all disease risk ...