Inhibition of YAP/TAZ-driven TEAD activity prevents growth of NF2-null schwannoma and meningioma.

Schwannoma tumours typically arise on the 8th cranial nerve and are mostly caused by loss of the tumour suppressor Merlin (NF2). There are no approved chemotherapies for these tumours and the surgical removal of the tumour carries a high risk of damage to the 8th or other close cranial nerve tissue. New treatments for schwannoma and other NF2-null tumours such as meningioma are urgently required. Using a combination of human primary tumour cells and mouse models of schwannoma, we have examined the role of the Hippo signalling pathway in driving tumour cell growth. Using both genetic ablation of the Hippo effectors YAP and TAZ as well as novel TEAD palmitoylation inhibitors, we show that Hippo signalling may be successfully targeted in vitro and in vivo to both block and, remarkably, regress schwannoma tumour growth. In particular, successful use of TEAD palmitoylation inhibitors in a pre-clinical mouse model of schwannoma points to their potential future clinical use. We also identify the cancer stem cell marker aldehyde dehydrogenase 1A1 (ALDH1A1) as a Hippo signalling target, driven by the TAZ protein in human and mouse NF2-null schwannoma cells, as well as in NF2-null meningioma cells, and examine the potential future role of this new target in halting schwannoma and meningioma tumour growth

The role of dipole interactions in hyperthermia heating colloidal clusters of densely-packed superparamagnetic nanoparticles

This work aims to investigate the influence of inter-particle dipole interactions on hyperthermia heating colloidal clusters of densely-packed Fe3O4 nanoparticles at low field intensity. Emulsion droplet solvent evaporation method was used to assemble oleic acid modified Fe3O4 particles into compact clusters which were stabilized by surfactant in water. Both experimental and simulation works were conducted to study their heating performance at different cluster’s sizes. The dipole interactions improve the heating only when the clusters are small enough to bring an enhancement in clusters’ shape anisotropy. The shape anisotropy is reduced at greater clusters’ sizes, since the shapes of the clusters become more and more spherical. Consequently, the dipole interactions change to impair the heating efficiency at larger sizes. When the clusters are totally isotropic in shape, the heating efficiency is lower than that of non-interacting particles despite the cluster’s size, although the efficiency increases by a little bit at a particular size most likely due to the dipole couplings. In these situations, one has to use particles with higher magnetic anisotropy and/or saturation magnetization to improve the heating

Auditory Deficit as a Consequence Rather than Endophenotype of Specific Language Impairment: Electrophysiological Evidence

Are developmental language disorders caused by poor auditory discrimination? This is a popular theory, but behavioural evidence has been inconclusive. Here we studied children with specific language impairment, measuring the brain's electrophysiological response to sounds in a passive paradigm. We focused on the T-complex, an event-related peak that has different origins and developmental course from the well-known vertex response.We analysed auditory event-related potentials to tones and syllables from 16 children and 16 adolescents with specific language impairment who were compared with 32 typically-developing controls, matched for gender, IQ and age.We replicated prior findings of significant reduction in Ta amplitude for both children and adolescents with specific language impairment, which was particularly marked for syllables. The topography of the T-complex to syllables indicated a less focal response in those with language impairments. To distinguish causal models, we considered correlations between size of the Ta response and measures of language and literacy in parents as well as children. The best-fitting model was one in which auditory deficit was a consequence rather than a cause of difficulties in phonological processing.The T-complex to syllables has abnormal size and topography in children with specific language impairment, but this is more likely to be a consequence rather than a cause of difficulties in phonological processing

Somatostatin analogues in the treatment of gastroenteropancreatic neuroendocrine tumours, current aspects and new perspectives

Gastroenteropancreatic neuroendocrine tumours (GEP NETs) are rare tumours that present many clinical features