RNA-seq analysis of Lgr6(+) stem cells and identification of an Lgr6 isoform

Dermatology-oncolog

The role of quiescent and cycling stem cells in the development of skin cancer

The incidence of skin carcinomas has been rising over the last decades. Ultraviolet (UV) radiation from the sun is the main exogenous risk factor. The principal premise underlying the present study is that stem cells are the primary targets of UV carcinogenesis. The aim of this study was to identify the main (stem) cell pool that drives this skin carcinogenesis. We studied cells in the interfollicular epidermis (IFE), quiescent stem cells and actively cycling Lgr5+ and Lgr6+ cells. Our data indicated that UV induced squamous cell carcinomas originate from the IFE. Furthermore, quiescent stem cells seem to play an important role in skin carcinogenesis. These cells accumulate DNA damage under chronic low level UV exposure. When we forced these DNA-damage retaining cells to proliferate, persistent (in situ) carcinomas developed. The actively cycling Lgr5+ and Lgr6+ cells did not seem to entail tumor-initiating stem cells in skin tumors induced by UV radiation or chemicals. We did not observe any tumors with substantial clonal expansion of Lgr5+ or Lgr6+ stem cells. Taken together, these results indicate that the continuously proliferating Lgr5+ and Lgr6+ stem cells are less vulnerable to cancerous transformation than quiescent stem cells. KWFLUMC / Geneeskund

Lgr5+stem cells and their progeny in mouse epidermis under regimens of exogenous skin carcinogenesis, and their absence in ensuing skin tumors

Dermatology-oncolog

Lgr5+and Lgr6+epidermal stem cells in mouse and man

Dermatology-oncolog

Lgr6+stem cells and their progeny in mouse epidermis under regimens of exogenous skin carcinogenesis, and their absence in ensuing skin tumors

Dermatology-oncolog

How European Fans in Training (EuroFIT), a lifestyle change program for men delivered in football clubs, achieved its effect: a mixed methods process evaluation embedded in a randomised controlled trial.

BACKGROUND: A randomised trial of European Fans in Training (EuroFIT), a 12-week healthy lifestyle program delivered in 15 professional football clubs in the Netherlands, Norway, Portugal, and the United Kingdom, successfully increased physical activity and improved diet but did not reduce sedentary time. To guide future implementation, this paper investigates how those effects were achieved. We ask: 1) how was EuroFIT implemented? 2) what were the processes through which outcomes were achieved? METHODS: We analysed qualitative data implementation notes, observations of 29 of 180 weekly EuroFIT deliveries, semi-structured interviews with 16 coaches and 15 club representatives, and 30 focus group discussions with participants (15 post-program and 15 after 12 months). We descriptively analysed quantitative data on recruitment, attendance at sessions and logs of use of the technologies and survey data on the views of participants at baseline, post program and after 12 months. We used a triangulation protocol to investigate agreement between data from difference sources, organised around meeting 15 objectives within the two research questions. RESULTS: We successfully recruited clubs, coaches and men to EuroFIT though the draw of the football club seemed stronger in the UK and Portugal. Advertising that emphasized getting fitter, club-based deliveries, and not 'standing out' worked and attendance and fidelity were good, so that coaches in all countries were able to deliver EuroFIT flexibly as intended. Coaches in all 15 clubs facilitated the use of behaviour change techniques and interaction between men, which together enhanced motivation. Participants found it harder to change sedentary time than physical activity and diet. Fitting changes into daily routines, planning for setbacks and recognising the personal benefit of behaviour change were important to maintain changes. Bespoke technologies were valued, but technological hitches frustrated participants. CONCLUSION: EuroFIT was delivered as planned by trained club coaches working flexibly in all countries. It worked as expected to attract men and support initiation and maintenance of changes in physical activity and diet but the use of bespoke, unstable, technologies was frustrating. Future deliveries should eliminate the focus on sedentary time and should use only proven technologies to support self-monitoring and social interaction. TRIAL REGISTRATION: ISRCTN81935608, registered 16/06/2015