Verbundprojekt: GeneSys: Vorstudie - Erprobung der Wasserfrac-Technik und des Einsonden-Zweischichtverfahrens für die Direktwärmenutzung aus gering permeablen Sedimentgesteinen : Abschlussbericht

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E-cigarettes versus nicotine replacement treatment as harm reduction interventions for smokers who find quitting difficult: Randomised controlled trial.

BACKGROUND AND AIMS: The majority of smokers accessing the current best treatments continue to smoke. We aimed to test if e-cigarettes (EC) compared with nicotine replacement treatment (NRT) can help such smokers reduce smoking. DESIGN: Randomised controlled trial of EC (n=68) vs NRT (n=67) with 6-month follow-up. SETTING: Stop smoking service in London, UK. PARTICIPANTS: 135 smokers (median age=40, 51% males) previously unable to stop smoking with conventional treatments. INTERVENTIONS: Participants received either NRT of their choice (8 week supply), or an EC starter pack and instructions to purchase further e-liquids of strength and flavours of their choice themselves. Products were accompanied by minimal behavioural support. MEASUREMENTS: Participants who reported that they stopped smoking or reduced their daily cigarette consumption by at least 50% at six-month follow-up were invited to provide a carbon monoxide (CO) reading. The primary outcome was biochemically validated reduction in smoke intake of at least 50% at 6 months and the main secondary outcome was sustained validated abstinence at 6 months. Drop-outs were included as 'non-reducers'. FINDINGS: Validated smoking reduction (including cessation) was achieved by 26.5% vs 6.0% of participants in the EC and NRT study arms, respectively (relative risk (RR)=4.4, p=0.005, 95% confidence interval (CI):1.6 to 12.4). Sustained validated abstinence rates at 6 months were 19.1% vs 3.0% (RR=6.4, p=0.01, 95%CI: 1.5 to 27.3). Product use was high and equal in both study arms initially, but at 6 months allocated product use was 47% in the EC arm vs 10% in the NRT arm (chi(1)=22.0, p<.001), respectively. Adverse events were minor and infrequent. CONCLUSIONS: In smokers unable to quit using conventional methods, e-cigarettes were more effective than nicotine replacement therapy in facilitating validated long-term smoking reduction and smoking cessation, when limited other support was provided

ΔNp63α expression induces loss of cell adhesion in triple-negative breast cancer cells

Background: p63, a member of the p53 protein family, plays key roles in epithelial development and carcinogenesis. In breast cancer, p63 expression has been found predominantly in basal-A (epithelial-type) triple-negative breast carcinomas (TNBC). To investigate the functional role of p63 in basal-A TNBC, we created MDA-MB-468 cell lines with inducible expression of the two major N-terminal p63 isoforms, TAp63α and ΔNp63α. Results: TAp63α did not have significant effect on gene expression profile and cell phenotype, whilst the main effect of ΔNp63α was reduction of cell adhesion. Gene expression profiling revealed genes involved in cell adhesion and migration whose expression relies on overexpression of ΔNp63α. Reduced cell adhesion also led to decreased cell proliferation in vitro and in vivo. Similar data were obtained in another basal-A cell line, BT-20, but not in BT-549 basal-B (mesenchymal-like) TNBC cells. Conclusions: In basal-A TNBC cells, ΔNp63α has much stronger effects on gene expression than TAp63α. Although p63 is mentioned mostly in connection with breast cell differentiation and stem cell regulation, we showed that a major effect of p63 is regulation of cell adhesion, a process important in metastasis and invasion of tumour cells. That this effect is not seen in mesenchymal-type TNBC cells suggests lineage-dependent functions, mirroring the expression of ΔNp63α in primary human breast cancers. © 2016 The Author(s)