Medical treatment of renal cancer: new horizons.

Renal cell carcinoma (RCC) makes up 2-3% of adult cancers. The introduction of tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin inhibitors in the mid-2000s radically changed the management of RCC. These targeted treatments superseded immunotherapy with interleukin-2 and interferon. The pendulum now appears to be shifting back towards immunotherapy, with the evidence of prolonged overall survival of patients with metastatic RCC on treatment with the anti-programmed cell death 1 ligand monoclonal antibody, nivolumab. Clinical prognostic criteria aid prediction of relapse risk for resected localised disease. Unfortunately, for patients at high risk of relapse, no adjuvant treatment has yet shown benefit, although further trials are yet to report. Clinical prognostic models also have a role in the management of advanced disease; now there is a pressing need for predictive biomarkers to direct therapy. Treatment selection for metastatic disease is currently based on histology, prognostic group and patient preference based on side effect profile. In this article, we review the current medical and surgical management of localised, oligometastatic and advanced RCC, including side effect management and the evidence base for management of poor-risk and non-clear cell disease. We discuss recent results from clinical trials and how these are likely to shape future practice and a renaissance of immunotherapy for renal cell cancer

SETD2 loss-of-function promotes renal cancer branched evolution through replication stress and impaired DNA repair

The research leading to these results is supported by Cancer Research UK (XYG, RAB, EG, PM, PE, SG, C Santos, AJR, NM, PAB, AS and C Swanton), Breast Cancer Research Foundation (C Swanton and NK), Medical Research Council (ID: G0902275 to MG and C Santos; ID: G0701935/2 to AJR and C Swanton), the Danish Cancer Society (AMM, J Bartkova and J Bartek), the Lundbeck Foundation (R93-A8990 to J Bartek), the Ministry of the interior of the Czech Republic (grant VG20102014001 to MM and J Bartek), the National Program of Sustainability (grant LO1304 to MM and J Bartek), the Danish Council for Independent Research (grant DFF-1331-00262 to J Bartek), NIHR RMH/ICR Biomedical Research Centre for Cancer (JL), the EC Framework 7 (PREDICT 259303 to XYG, EG, PM, MG, TJ and C Swanton; DDResponse 259892 to J Bartek and J Bartkova and RESPONSIFY ID:259303 to C Swanton), UCL Overseas Research Scholarship (SG). C Swanton is also supported by the European Research Council, Rosetrees Trust and The Prostate Cancer Foundation. This research is supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre

Improving performance of fully scalable, flexible transparent conductive films made from carbon nanotubes and ethylene-vinyl acetate

We report process improvements for the fabrication of single-walled carbon nanotube ethylene-vinyl acetate transparent conductive films. CNT:EVA films demonstrate high resilience against folding and can replace the external dopant in a spiro-OMeTAD based hole selective contact of n-i-p perovskite solar cells achieving a steady-state efficiency of 16.3%. The adapted process is fully scalable, and compared to previous reports (Mazzotta et al., 2018) lowers the material cost dramatically and improves DC to optical conductivity ratio by two orders of magnitude to σdc/σop = 3.6 for pristine and σdc/σop = 15 for chemically doped films. We analyse the microstructure of our films via small angle neutron scattering and find a positive correlation between the long range packing density of the CNT:EVA films and the σdc/σop performance. Increasing monomer ratio and chain length of the EVA polymer improves resilience against bending strain, whereas no significant effect on the CNT wrapping and electrical conductivity of resulting films is found

Structure and dynamics of phospholipid bilayer films under electrochemical control

Vesicle fusion was used to deposit mixed dimyristoyl phosphatidylethanolamine-dimyristoyl phosphatidylserine (DMPE-DMPS) phospholipid bilayers on Au electrodes. Bilayer structure and composition, when exposed to aqueous NaF and subject to an applied electrochemical potential, were studied using electrochemical, spectroscopic and neutron reflectivity (NR) techniques. Interfacial capacitance data indicate the formation of compact films. Chronocolometric data show that surface charge is significantly altered by the presence of lipid in the potential range -0.75 < E/V (Ag vertical bar AgCl) < 0.35. NR measurements were made on lipid films in which the hydrocarbon tails were either fully hydrogenous (h-DMPE-h-DMPS) or perdeuterated (d-DMPE-d-DMPS), in each case serially exposed to D2O and H2O electrolytes and subject to different applied potentials. Guided by simulations of candidate interfacial structures, these yield the spatial distributions of lipid and solvent within the layers. Adjacent to the electrode, a compact inner leaflet is formed, with potential-dependent solvent volume fraction in the range 0.09 < phi(S) < 0.19; there was no evidence of an intervening water layer. The outer leaflet contains rather more solvent, 0.52 < phi(S) < 0.55. NR-derived film thickness and PM-IRRAS intensity data show that the lipid molecules are tilted from the surface normal by ca. 26 degrees. Bilayer solvation and charge data show a strong correlation for the inner leaflet and very little for the outer leaflet