Sox2 promotes tamoxifen resistance in breast cancer cells

Development of resistance to therapy continues to be a serious clinical problem in breast cancer management. Cancer stem/progenitor cells have been shown to play roles in resistance to chemo- and radiotherapy. Here, we examined their role in the development of resistance to the oestrogen receptor antagonist tamoxifen. Tamoxifen-resistant cells were enriched for stem/progenitors and expressed high levels of the stem cell marker Sox2. Silencing of the SOX2 gene reduced the size of the stem/progenitor cell population and restored sensitivity to tamoxifen. Conversely, ectopic expression of Sox2 reduced tamoxifen sensitivity in vitro and in vivo. Gene expression profiling revealed activation of the Wnt signalling pathway in Sox2-expressing cells, and inhibition of Wnt signalling sensitized resistant cells to tamoxifen. Examination of patient tumours indicated that Sox2 levels are higher in patients after endocrine therapy failure, and also in the primary tumours of these patients, compared to those of responders. Together, these results suggest that development of tamoxifen resistance is driven by Sox2-dependent activation of Wnt signalling in cancer stem/progenitor cells

Population-based colorectal cancer screening programmes using a faecal immunochemical test:Should faecal haemoglobin cut-offs differ by age and sex?

Abstract Background The Basque Colorectal Cancer Screening Programme has both high participation rate and high compliance rate of colonoscopy after a positive faecal occult blood test (FIT). Although, colorectal cancer (CRC) screening with biannual (FIT) has shown to reduce CRC mortality, the ultimate effectiveness of the screening programmes depends on the accuracy of FIT and post-FIT colonoscopy, and thus, harms related to false results might not be underestimated. Current CRC screening programmes use a single faecal haemoglobin concentration (f-Hb) cut-off for colonoscopy referral for both sexes and all ages. We aimed to determine optimum f-Hb cut-offs by sex and age without compromising neoplasia detection and interval cancer proportion. Methods Prospective cohort study using a single-sample faecal immunochemical test (FIT) on 444,582 invited average-risk subjects aged 50–69 years. A result was considered positive at ≥20 μg Hb/g faeces. Outcome measures were analysed by sex and age for a wide range of f-Hb cut-offs. Results We analysed 17,387 positive participants in the programme who underwent colonoscopy. Participation rate was 66.5%. Men had a positivity rate for f-Hb of 8.3% and women 4.8% (p < 0.0001). The detection rate for advanced neoplasia (cancer plus advanced adenoma) was 44.0‰ for men and 15.9‰ for women (p < 0.0001). The number of colonoscopies required decreased in both sexes and all age groups through increasing the f-Hb cut-off. However, the loss in CRC detection increased by up to 28.1% in men and 22.9% in women. CRC missed were generally at early stages (Stage I-II: from 70.2% in men to 66.3% in women). Conclusions This study provides detailed outcomes in men and women of different ages at a range of f-Hb cut-offs. We found differences in positivity rates, neoplasia detection rate, number needed to screen, and interval cancers in men and women and in younger and older groups. However, there are factors other than sex and age to consider when consideration is given to setting the f-Hb cut-off

Arte Cisoria

Arte Cisoria completa una trilogía, junto con “Gliptodonte. Visiones a través del arte” y “Argentina. Arte y Paleontología”, de investigaciones artísticas que plantean distintas alternativas para profundizar en el proceso creativo de la imagen. Arte Cisoria es el desencadenante de este proyecto. Es el punto de partida y de referencia para las propuestas creativas de los artistas que han participado en el mismo. El secreto está en el corte. Arte Cisoria nos habla del arte de cortar, recortar, trinchar, escindir, etc. y a la vez nos sugiere el uso de herramientas como cuchillos, tijeras, escalpelos, cuchillas de afeitar, mas allá del propio tratado. En las imágenes realizadas por cada uno de los artistas participantes se da rienda suelta a su creatividad. Este proyecto pretende aportar una nueva metodología de enfoque en el proceso artístico, que sirva como un elemento auxiliar de creación para ofrecer unos resultados más ricos, complejos e interesantes, mediante la serigrafía digital.Universidad de Salamanca, Instituto Universitario de Investigación en Arte y Tecnología de la Animación de la Universidad de Salamanca (ATA), Diputación de Alicante, Instituto Alicantino de Cultura Juan Gil-Albert, Ayuntamiento de Albacete, Casa Falconieri, Museo de la Cuchillería de Albacete (MCA), Canson, Artemiranda, Iberoprinter, Universidad Autónoma de Ciudad Juárez

Euskara sustatzeko eleaniztasuna: ikastolen kasua

En este artículo presentaremos las bases y los resultados del "plurilingüismo articulado en torno al euskara", puesto en marcha por las ikastolas, y mencionaremos las conclusiones del camino realizado por las ikastolas en el desarrollo de ese modelo escolar plurilingüe y las líneas a seguir cara al futuro.Artikulu honetan Ikastolek abian duten "euskaran ardaztutako eleaniztasuna"ren oinarriak eta emaitzak aurkeztu eta eskola eredu eleanitz horren garapean Ikastolek egin duten bidearen ondorioak nahiz etorkizunerako ildoak aipatuko ditugu.Cet article présente les fondement s et les résultat s du "plurilinguisme articulé autour de l'euskara", mis en oeuvre par les ikastolas, ainsi que les conclusions du travail réalisé par les ikastolas pour le développement du modèle d'école plurilingue, ainsi que les lignes directrices à suivre face l'avenir.This paper presents the bases and result s of the scheme "Multilingualism around the hub of Basque" launched by the Basque-medium schools or Ikastolas, and deals not only with the consequences of the way paved by the Ikastolas in the development of this multilingual school model, but also with the lines for the future