Discovery of the SMYD3 Inhibitor BAY-6035 Using Thermal Shift Assay (TSA)-Based High-Throughput Screening.

SMYD3 (SET and MYND domain-containing protein 3) is a protein lysine methyltransferase that was initially described as an H3K4 methyltransferase involved in transcriptional regulation. SMYD3 has been reported to methylate and regulate several nonhistone proteins relevant to cancer, including mitogen-activated protein kinase kinase kinase 2 (MAP3K2), vascular endothelial growth factor receptor 1 (VEGFR1), and the human epidermal growth factor receptor 2 (HER2). In addition, overexpression of SMYD3 has been linked to poor prognosis in certain cancers, suggesting SMYD3 as a potential oncogene and attractive cancer drug target.

Author Correction: Pharmacological inhibition of PRMT7 links arginine monomethylation to the cellular stress response.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Pharmacological inhibition of PRMT7 links arginine monomethylation to the cellular stress response.

Protein arginine methyltransferases (PRMTs) regulate diverse biological processes and are increasingly being recognized for their potential as drug targets. Here we report the discovery of a potent, selective, and cell-active chemical probe for PRMT7. SGC3027 is a cell permeable prodrug, which in cells is converted to SGC8158, a potent, SAM-competitive PRMT7 inhibitor.

Parenting Science Gang: radical co-creation of research projects led by parents of young children.

Background: Parents are increasingly searching online for information supported by research but can find it difficult to identify results relevant to their own experiences. More troublingly, a number of studies indicate that parenting information found online often can be misleading or wrong. The goal of the Parenting Science Gang (PSG) project was to use the power of the Internet to help parents ask questions they wanted to have answered by scientific research and to feel confident in assessing research evidence.

Discovery of a chemical probe for PRDM9.

PRDM9 is a PR domain containing protein which trimethylates histone 3 on lysine 4 and 36. Its normal expression is restricted to germ cells and attenuation of its activity results in altered meiotic gene transcription, impairment of double-stranded breaks and pairing between homologous chromosomes. There is growing evidence for a role of aberrant expression of PRDM9 in oncogenesis and genome instability.

Assay interference and off-target liabilities of reported histone acetyltransferase inhibitors.

Many compounds with potentially reactive chemical motifs and poor physicochemical properties are published as selective modulators of biomolecules without sufficient validation and then propagated in the scientific literature as useful chemical probes. Several histone acetyltransferase (HAT) inhibitors with these liabilities are now routinely used to probe epigenetic pathways. We profile the most commonly used HAT inhibitors and confirm that the majority of them are nonselective interference compounds.

TRIM14 is a Putative Tumor Suppressor and Regulator of Innate Immune Response in Non-Small Cell Lung Cancer.

Non-small-cell lung carcinoma (NSCLC) accounts for 85% of malignant lung tumors and is the leading cause of cancer deaths. Our group previously identified Tripartite Motif 14 (TRIM14) as a component of a prognostic multigene expression signature for NSCLC. Little is known about the function of TRIM14 protein in normal or disease states.

[DIAGNOSIS AND TREATMENT OF ESOPHAGEAL INJURY].

Results of diagnosis and treatment of 19 injured persons, suffering esophageal damage of various etiology, were analyzed.Peculiarities of clinical signs and diagnosis of esophageal injury on various levels and complications were investigated. Various methods of the injured persons’ treatment, concerning the damage character, terms of appeal for medical care, presence of complications and concurrent diseases, were adduced.

p120RasGAP is a mediator of rho pathway activation and tumorigenicity in the DLD1 colorectal cancer cell line.

KRAS is mutated in ∼40% of colorectal cancer (CRC), and there are limited effective treatments for advanced KRAS mutant CRC. Therefore, it is crucial that downstream mediators of oncogenic KRAS continue to be studied. We identified p190RhoGAP as being phosphorylated in the DLD1 CRC cell line, which expresses a heterozygous KRAS G13D allele, and not in DKO4 in which the mutant allele has been deleted by somatic recombination.

An overview of the c-MET signaling pathway.

c-MET is a receptor tyrosine kinase that, after binding with its ligand, hepatocyte growth factor, activates a wide range of different cellular signaling pathways, including those involved in proliferation, motility, migration and invasion. Although c-MET is important in the control of tissue homeostasis under normal physiological conditions, it has also been found to be aberrantly activated in human cancers via mutation, amplification or protein overexpression. This paper provides an overview of the c-MET signaling pathway, including its role in the development of cancers, and provides a rationale for targeting the pathway as a possible treatment option.

Quantitative phospho-proteomic profiling of hepatocyte growth factor (HGF)-MET signaling in colorectal cancer.

Colorectal cancer (CRC) is the second leading cause of death from cancer. The MET receptor tyrosine kinase and/or its ligand HGF are frequently amplified or overexpressed in CRC. It is known that tyrosine phosphorylated proteins are involved in progression and metastasis of colorectal cancer; however, little is known about the MET phospho-proteome in CRC.

Co-overexpression of Met and hepatocyte growth factor promotes systemic metastasis in NCI-H460 non-small cell lung carcinoma cells.

Complete resection of early-stage non-small cell lung cancer (NSCLC) is potentially curative, yet approximately 50% of patients are at risk for developing metastatic recurrence. Met, the receptor for hepatocyte growth factor (HGF) is a receptor tyrosine kinase with demonstrated roles in regulating cellular proliferation, motility, morphogenesis, and apoptosis. Met receptor and its ligand, HGF, are commonly overexpressed in NSCLC, and their overexpression has been associated with poor prognosis, which could potentially involve a paracrine and/or autocrine activation loop.

Src and FAK mediate cell-matrix adhesion-dependent activation of Met during transformation of breast epithelial cells.

Cell-matrix adhesion has been shown to promote activation of the hepatocyte growth factor receptor, Met, in a ligand-independent manner. This process has been linked to transformation and tumorigenesis in a variety of cancer types. In the present report, we describe a key role of integrin signaling via the Src/FAK axis in the activation of Met in breast epithelial and carcinoma cells.

Is STI surveillance in England meeting the requirements of the 21st century? An evaluation of data from the South West Region.

This study evaluates two sexually transmitted infections (STI) surveillance systems' ability to provide relevant, accurate, and timely information to inform prevention and control activities in England, using data from the South West, the largest of the country's nine regions. The systems were evaluated in terms of timeliness of reporting to subsequent levels; frequency of reporting and feedback; completeness of information in the reports; and representativeness of the reports to the resident population. To determine the usefulness of the system for those responsible for taking public health action, semi-structured interviews of a sample of users of surveillance information were conducted.

Salvage surgery for lateral tennis elbow.

We undertook a retrospective analysis of 34 patients (35 elbows) who had prior failed surgical intervention for lateral tennis elbow. Revision surgeries were performed between 1979 and 1994. Each patient's non-operative and operative history was recorded before our salvage revision surgery.

Arthroscopic transglenoid suture capsulolabral repair. Five-year followup.

The preliminary results of our arthroscopic transglenoid suture capsulolabral repair demonstrated a failure rate of only 10%, with no postoperative dislocations. The purpose of this study was to reevaluate a patient population with a 5-year minimum followup similar to the one previously reported with a 2-year followup. We performed a retrospective analysis of 38 shoulders in 37 consecutive patients who underwent arthroscopic transglenoid suture capsulolabral repair between January 1989 and June 1990.

Out of a job.

I am a qualified RGN with experience in Paediatrics Gynae and Orthopaedics yet when I went for a job recently I was told that, as I have not worked within the National Health Service for four years my last NHS reference could not be taken into consideration for the job as a full time staff nurse, despite the fact that it was excellent.