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Integration of RNAi and Small Molecule Screens to Identify Targets for Drug Development.
(2019-01)
Cellular models for siRNA and small molecule high-throughput screening have been widely used in the last decade to identify targets for drug discovery. As an example, we present a twofold readout approach based on cell ...
Cells Lacking the RB1 Tumor Suppressor Gene Are Hyperdependent on Aurora B Kinase for Survival.
(AMER ASSOC CANCER RESEARCH, 2019-02-01)
Small cell lung cancer (SCLC) accounts for 15% of lung cancers and is almost always linked to inactivating RB1 and TP53 mutations. SCLC frequently responds, albeit briefly, to chemotherapy. The canonical function of the ...
RIPK1 and Caspase-8 Ensure Chromosome Stability Independently of Their Role in Cell Death and Inflammation.
(CELL PRESS, 2019-02-07)
Receptor-interacting protein kinase (RIPK) 1 functions as a key mediator of tissue homeostasis via formation of Caspase-8 activating ripoptosome complexes, positively and negatively regulating apoptosis, necroptosis, and ...
The anticonvulsive Phenhydan® suppresses extrinsic cell death.
(NATURE PUBLISHING GROUP, 2019-09-01)
Different forms of regulated cell death-like apoptosis and necroptosis contribute to the pathophysiology of clinical conditions including ischemia-reperfusion injury, myocardial infarction, sepsis, and multiple sclerosis. ...
Metabolism of the dual FLT-3/Aurora kinase inhibitor CCT241736 in preclinical and human in vitro models: Implication for the choice of toxicology species.
(ELSEVIER, 2019-11-01)
CCT241736 is a dual fms-like tyrosine kinase 3 (FLT3)/Aurora kinase inhibitor in development for the treatment of acute myeloid leukaemia. The successful development of any new drug relies on adequate safety testing including ...
Breast cancer risk prediction in women aged 35-50 years: impact of including sex hormone concentrations in the Gail model.
(BMC, 2019-03-19)
BACKGROUND: Models that accurately predict risk of breast cancer are needed to help younger women make decisions about when to begin screening. Premenopausal concentrations of circulating anti-Müllerian hormone (AMH), a ...
Using an in-vivo syngeneic spontaneous metastasis model identifies ID2 as a promoter of breast cancer colonisation in the brain.
(BMC, 2019-01-14)
BACKGROUND: Dissemination of breast cancers to the brain is associated with poor patient outcome and limited therapeutic options. In this study we sought to identify novel regulators of brain metastasis by profiling mouse ...
Hotspot SF3B1 mutations induce metabolic reprogramming and vulnerability to serine deprivation.
(AMER SOC CLINICAL INVESTIGATION INC, 2019-08-08)
Cancer-associated mutations in the spliceosome gene SF3B1 create a neomorphic protein that produces aberrant mRNA splicing in hundreds of genes, but the ensuing biologic and therapeutic consequences of this missplicing are ...
C/EBPα mediates the growth inhibitory effect of progestins on breast cancer cells.
(WILEY, 2019-09-16)
Steroid hormones are key gene regulators in breast cancer cells. While estrogens stimulate cell proliferation, progestins activate a single cell cycle followed by proliferation arrest. Here, we use biochemical and genome-wide ...
The Lineage Determining Factor GRHL2 Collaborates with FOXA1 to Establish a Targetable Pathway in Endocrine Therapy-Resistant Breast Cancer.
(CELL PRESS, 2019-10-22)
Notwithstanding the positive clinical impact of endocrine therapies in estrogen receptor-alpha (ERα)-positive breast cancer, de novo and acquired resistance limits the therapeutic lifespan of existing drugs. Taking the ...