Homeostatic proliferation and survival of naïve and memory T cells.

The immune system relies on homeostatic mechanisms in order to adapt to the changing requirements encountered during steady-state existence and activation by antigen. For T cells, this involves maintenance of a diverse repertoire of naïve cells, rapid elimination of effector cells after pathogen clearance, and long-term survival of memory cells. The reduction of T-cell counts by either cytotoxic drugs, irradiation, or certain viruses is known to lead to lymphopenia-induced proliferation and restoration of normal T-cell levels. Such expansion is governed by the interaction of TCR with self-peptide/MHC (p/MHC) molecules plus contact with cytokines, especially IL-7. These same ligands, i.e. p/MHC molecules and IL-7, maintain naïve T lymphocytes as resting cells under steady-state T-cell-sufficient conditions. Unlike naïve cells, typical "central" memory T cells rely on a combination of IL-7 and IL-15 for their survival in interphase and for occasional cell division without requiring signals from p/MHC molecules. Other memory T-cell subsets are less quiescent and include naturally occurring activated memory-phenotype cells, memory cells generated during chronic viral infections, and effector memory cells. These subsets of activated memory cells differ from central memory T cells in their requirements for homeostatic proliferation and survival. Thus, the factors controlling T-cell homeostasis can be seen to vary considerably from one subset to another as described in detail in this review.

Linking landscape- and population ecology for large population management modelling: the case of Ibex (capra ibex) in Switzerland

La biologie de la conservation est communément associée à la protection de petites populations menacées d?extinction. Pourtant, il peut également être nécessaire de soumettre à gestion des populations surabondantes ou susceptibles d?une trop grande expansion, dans le but de prévenir les effets néfastes de la surpopulation. Du fait des différences tant quantitatives que qualitatives entre protection des petites populations et contrôle des grandes, il est nécessaire de disposer de modèles et de méthodes distinctes. L?objectif de ce travail a été de développer des modèles prédictifs de la dynamique des grandes populations, ainsi que des logiciels permettant de calculer les paramètres de ces modèles et de tester des scénarios de gestion. Le cas du Bouquetin des Alpes (Capra ibex ibex) - en forte expansion en Suisse depuis sa réintroduction au début du XXème siècle - servit d?exemple. Cette tâche fut accomplie en trois étapes : En premier lieu, un modèle de dynamique locale, spécifique au Bouquetin, fut développé : le modèle sous-jacent - structuré en classes d?âge et de sexe - est basé sur une matrice de Leslie à laquelle ont été ajoutées la densité-dépendance, la stochasticité environnementale et la chasse de régulation. Ce modèle fut implémenté dans un logiciel d?aide à la gestion - nommé SIM-Ibex - permettant la maintenance de données de recensements, l?estimation automatisée des paramètres, ainsi que l?ajustement et la simulation de stratégies de régulation. Mais la dynamique d?une population est influencée non seulement par des facteurs démographiques, mais aussi par la dispersion et la colonisation de nouveaux espaces. Il est donc nécessaire de pouvoir modéliser tant la qualité de l?habitat que les obstacles à la dispersion. Une collection de logiciels - nommée Biomapper - fut donc développée. Son module central est basé sur l?Analyse Factorielle de la Niche Ecologique (ENFA) dont le principe est de calculer des facteurs de marginalité et de spécialisation de la niche écologique à partir de prédicteurs environnementaux et de données d?observation de l?espèce. Tous les modules de Biomapper sont liés aux Systèmes d?Information Géographiques (SIG) ; ils couvrent toutes les opérations d?importation des données, préparation des prédicteurs, ENFA et calcul de la carte de qualité d?habitat, validation et traitement des résultats ; un module permet également de cartographier les barrières et les corridors de dispersion. Le domaine d?application de l?ENFA fut exploré par le biais d?une distribution d?espèce virtuelle. La comparaison à une méthode couramment utilisée pour construire des cartes de qualité d?habitat, le Modèle Linéaire Généralisé (GLM), montra qu?elle était particulièrement adaptée pour les espèces cryptiques ou en cours d?expansion. Les informations sur la démographie et le paysage furent finalement fusionnées en un modèle global. Une approche basée sur un automate cellulaire fut choisie, tant pour satisfaire aux contraintes du réalisme de la modélisation du paysage qu?à celles imposées par les grandes populations : la zone d?étude est modélisée par un pavage de cellules hexagonales, chacune caractérisée par des propriétés - une capacité de soutien et six taux d?imperméabilité quantifiant les échanges entre cellules adjacentes - et une variable, la densité de la population. Cette dernière varie en fonction de la reproduction et de la survie locale, ainsi que de la dispersion, sous l?influence de la densité-dépendance et de la stochasticité. Un logiciel - nommé HexaSpace - fut développé pour accomplir deux fonctions : 1° Calibrer l?automate sur la base de modèles de dynamique (par ex. calculés par SIM-Ibex) et d?une carte de qualité d?habitat (par ex. calculée par Biomapper). 2° Faire tourner des simulations. Il permet d?étudier l?expansion d?une espèce envahisseuse dans un paysage complexe composé de zones de qualité diverses et comportant des obstacles à la dispersion. Ce modèle fut appliqué à l?histoire de la réintroduction du Bouquetin dans les Alpes bernoises (Suisse). SIM-Ibex est actuellement utilisé par les gestionnaires de la faune et par les inspecteurs du gouvernement pour préparer et contrôler les plans de tir. Biomapper a été appliqué à plusieurs espèces (tant végétales qu?animales) à travers le Monde. De même, même si HexaSpace fut initialement conçu pour des espèces animales terrestres, il pourrait aisément être étndu à la propagation de plantes ou à la dispersion d?animaux volants. Ces logiciels étant conçus pour, à partir de données brutes, construire un modèle réaliste complexe, et du fait qu?ils sont dotés d?une interface d?utilisation intuitive, ils sont susceptibles de nombreuses applications en biologie de la conservation. En outre, ces approches peuvent également s?appliquer à des questions théoriques dans les domaines de l?écologie des populations et du paysage.<br/><br/>Conservation biology is commonly associated to small and endangered population protection. Nevertheless, large or potentially large populations may also need human management to prevent negative effects of overpopulation. As there are both qualitative and quantitative differences between small population protection and large population controlling, distinct methods and models are needed. The aim of this work was to develop theoretical models to predict large population dynamics, as well as computer tools to assess the parameters of these models and to test management scenarios. The alpine Ibex (Capra ibex ibex) - which experienced a spectacular increase since its reintroduction in Switzerland at the beginning of the 20th century - was used as paradigm species. This task was achieved in three steps: A local population dynamics model was first developed specifically for Ibex: the underlying age- and sex-structured model is based on a Leslie matrix approach with addition of density-dependence, environmental stochasticity and culling. This model was implemented into a management-support software - named SIM-Ibex - allowing census data maintenance, parameter automated assessment and culling strategies tuning and simulating. However population dynamics is driven not only by demographic factors, but also by dispersal and colonisation of new areas. Habitat suitability and obstacles modelling had therefore to be addressed. Thus, a software package - named Biomapper - was developed. Its central module is based on the Ecological Niche Factor Analysis (ENFA) whose principle is to compute niche marginality and specialisation factors from a set of environmental predictors and species presence data. All Biomapper modules are linked to Geographic Information Systems (GIS); they cover all operations of data importation, predictor preparation, ENFA and habitat suitability map computation, results validation and further processing; a module also allows mapping of dispersal barriers and corridors. ENFA application domain was then explored by means of a simulated species distribution. It was compared to a common habitat suitability assessing method, the Generalised Linear Model (GLM), and was proven better suited for spreading or cryptic species. Demography and landscape informations were finally merged into a global model. To cope with landscape realism and technical constraints of large population modelling, a cellular automaton approach was chosen: the study area is modelled by a lattice of hexagonal cells, each one characterised by a few fixed properties - a carrying capacity and six impermeability rates quantifying exchanges between adjacent cells - and one variable, population density. The later varies according to local reproduction/survival and dispersal dynamics, modified by density-dependence and stochasticity. A software - named HexaSpace - was developed, which achieves two functions: 1° Calibrating the automaton on the base of local population dynamics models (e.g., computed by SIM-Ibex) and a habitat suitability map (e.g. computed by Biomapper). 2° Running simulations. It allows studying the spreading of an invading species across a complex landscape made of variously suitable areas and dispersal barriers. This model was applied to the history of Ibex reintroduction in Bernese Alps (Switzerland). SIM-Ibex is now used by governmental wildlife managers to prepare and verify culling plans. Biomapper has been applied to several species (both plants and animals) all around the World. In the same way, whilst HexaSpace was originally designed for terrestrial animal species, it could be easily extended to model plant propagation or flying animals dispersal. As these softwares were designed to proceed from low-level data to build a complex realistic model and as they benefit from an intuitive user-interface, they may have many conservation applications. Moreover, theoretical questions in the fields of population and landscape ecology might also be addressed by these approaches.

The role of smoking in changes in the survival curve: an empirical study in 10 European countries.

PURPOSE: We examined the role of smoking in the two dimensions behind the time trends in adult mortality in European countries, that is, rectangularization of the survival curve (mortality compression) and longevity extension (increase in the age-at-death). METHODS: Using data on national sex-specific populations aged 50 years and older from Denmark, Finland, France, West Germany, Italy, the Netherlands, Norway, Sweden, Switzerland, and the United Kingdom, we studied trends in life expectancy, rectangularity, and longevity from 1950 to 2009 for both all-cause and nonsmoking-related mortality and correlated them with trends in lifetime smoking prevalence. RESULTS: For all-cause mortality, rectangularization accelerated around 1980 among men in all the countries studied, and more recently among women in Denmark and the United Kingdom. Trends in lifetime smoking prevalence correlated negatively with both rectangularization and longevity extension, but more negatively with rectangularization. For nonsmoking-related mortality, rectangularization among men did not accelerate around 1980. Among women, the differences between all-cause mortality and nonsmoking-related mortality were small, but larger for rectangularization than for longevity extension. Rectangularization contributed less to the increase in life expectancy than longevity extension, especially for nonsmoking-related mortality among men. CONCLUSIONS: Smoking affects rectangularization more than longevity extension, both among men and women.

Low C-reactive protein values at admission predict mortality in patients with severe community-acquired pneumonia caused by Streptococcus pneumoniae that require intensive care management.

PURPOSE: To identify risk factors associated with mortality in patients with severe community-acquired pneumonia (CAP) caused by S. pneumoniae who require intensive care unit (ICU) management, and to assess the prognostic values of these risk factors at the time of admission. METHODS: Retrospective analysis of all consecutive patients with CAP caused by S. pneumoniae who were admitted to the 32-bed medico-surgical ICU of a community and referral university hospital between 2002 and 2011. Univariate and multivariate analyses were performed on variables available at admission. RESULTS: Among the 77 adult patients with severe CAP caused by S. pneumoniae who required ICU management, 12 patients died (observed mortality rate 15.6 %). Univariate analysis indicated that septic shock and low C-reactive protein (CRP) values at admission were associated with an increased risk of death. In a multivariate model, after adjustment for age and gender, septic shock [odds ratio (OR), confidence interval 95 %; 4.96, 1.11-22.25; p = 0.036], and CRP (OR 0.99, 0.98-0.99 p = 0.034) remained significantly associated with death. Finally, we assessed the discriminative ability of CRP to predict mortality by computing its receiver operating characteristic curve. The CRP value cut-off for the best sensitivity and specificity was 169.5 mg/L to predict hospital mortality with an area under the curve of 0.72 (0.55-0.89). CONCLUSIONS: The mortality of patients with S. pneumoniae CAP requiring ICU management was much lower than predicted by severity scores. The presence of septic shock and a CRP value at admission <169.5 mg/L predicted a fatal outcome.

The anticancer drug metabolites endoxifen and 4-hydroxy-tamoxifen induce toxic effects on Daphnia pulex in a two-generation study.

Although pharmaceutical metabolites are found in the aquatic environment, their toxicity on living organisms is poorly studied in general. Endoxifen and 4-hydroxy-tamoxifen (4OHTam) are two metabolites of the widely used anticancer drug tamoxifen for the prevention and treatment of breast cancers. Both metabolites have a high pharmacological potency in vertebrates, attributing prodrug characteristics to tamoxifen. Tamoxifen and its metabolites are body-excreted by patients, and the parent compound is found in sewage treatment plan effluents and natural waters. The toxicity of these potent metabolites on non-target aquatic species is unknown, which forces environmental risk assessors to predict their toxicity on aquatic species using knowledge on the parent compounds. Therefore, the aim of this study was to assess the sensitivity of two generations of the freshwater microcrustacean Daphnia pulex towards 4OHTam and endoxifen. Two chronic tests of 4OHTam and endoxifen were run in parallel and several endpoints were assessed. The results show that the metabolites 4OHTam and endoxifen induced reproductive and survival effects. For both metabolites, the sensitivity of D. pulex increased in the second generation. The intrinsic rate of natural increase (r) decreased with increasing 4OHTam and endoxifen concentrations. The No-Observed Effect Concentrations (NOECs) calculated for the reproduction of the second generation exposed to 4OHTam and endoxifen were <1.8 and 4.3μg/L, respectively, whereas the NOECs that were calculated for the intrinsic rate of natural increase were <1.8 and 0.4μg/L, respectively. Our study raises questions about prodrug and active metabolites in environmental toxicology assessments of pharmaceuticals. Our findings also emphasize the importance of performing long-term experiments and considering multi-endpoints instead of the standard reproduction outcome.

Global surveillance of cancer survival 1995-2009 : analysis of individual data for 25 676 887 patients from 279 population-based registries in 67 countries (CONCORD-2)

BACKGROUND: Worldwide data for cancer survival are scarce. We aimed to initiate worldwide surveillance of cancer survival by central analysis of population-based registry data, as a metric of the effectiveness of health systems, and to inform global policy on cancer control. METHODS: Individual tumour records were submitted by 279 population-based cancer registries in 67 countries for 25·7 million adults (age 15-99 years) and 75 000 children (age 0-14 years) diagnosed with cancer during 1995-2009 and followed up to Dec 31, 2009, or later. We looked at cancers of the stomach, colon, rectum, liver, lung, breast (women), cervix, ovary, and prostate in adults, and adult and childhood leukaemia. Standardised quality control procedures were applied; errors were corrected by the registry concerned. We estimated 5-year net survival, adjusted for background mortality in every country or region by age (single year), sex, and calendar year, and by race or ethnic origin in some countries. Estimates were age-standardised with the International Cancer Survival Standard weights. FINDINGS: 5-year survival from colon, rectal, and breast cancers has increased steadily in most developed countries. For patients diagnosed during 2005-09, survival for colon and rectal cancer reached 60% or more in 22 countries around the world; for breast cancer, 5-year survival rose to 85% or higher in 17 countries worldwide. Liver and lung cancer remain lethal in all nations: for both cancers, 5-year survival is below 20% everywhere in Europe, in the range 15-19% in North America, and as low as 7-9% in Mongolia and Thailand. Striking rises in 5-year survival from prostate cancer have occurred in many countries: survival rose by 10-20% between 1995-99 and 2005-09 in 22 countries in South America, Asia, and Europe, but survival still varies widely around the world, from less than 60% in Bulgaria and Thailand to 95% or more in Brazil, Puerto Rico, and the USA. For cervical cancer, national estimates of 5-year survival range from less than 50% to more than 70%; regional variations are much wider, and improvements between 1995-99 and 2005-09 have generally been slight. For women diagnosed with ovarian cancer in 2005-09, 5-year survival was 40% or higher only in Ecuador, the USA, and 17 countries in Asia and Europe. 5-year survival for stomach cancer in 2005-09 was high (54-58%) in Japan and South Korea, compared with less than 40% in other countries. By contrast, 5-year survival from adult leukaemia in Japan and South Korea (18-23%) is lower than in most other countries. 5-year survival from childhood acute lymphoblastic leukaemia is less than 60% in several countries, but as high as 90% in Canada and four European countries, which suggests major deficiencies in the management of a largely curable disease. INTERPRETATION: International comparison of survival trends reveals very wide differences that are likely to be attributable to differences in access to early diagnosis and optimum treatment. Continuous worldwide surveillance of cancer survival should become an indispensable source of information for cancer patients and researchers and a stimulus for politicians to improve health policy and health-care systems. FUNDING: Canadian Partnership Against Cancer (Toronto, Canada), Cancer Focus Northern Ireland (Belfast, UK), Cancer Institute New South Wales (Sydney, Australia), Cancer Research UK (London, UK), Centers for Disease Control and Prevention (Atlanta, GA, USA), Swiss Re (London, UK), Swiss Cancer Research foundation (Bern, Switzerland), Swiss Cancer League (Bern, Switzerland), and University of Kentucky (Lexington, KY, USA).

Meckel-Gruber Syndrome: a population-based study on prevalence, prenatal diagnosis, clinical features, and survival in Europe.

Meckel-Gruber Syndrome is a rare autosomal recessive lethal ciliopathy characterized by the triad of cystic renal dysplasia, occipital encephalocele and postaxial polydactyly. We present the largest population-based epidemiological study to date using data provided by the European Surveillance of Congenital Anomalies (EUROCAT) network. The study population consisted of 191 cases of MKS identified between January 1990 and December 2011 in 34 European registries. The mean prevalence was 2.6 per 100 000 births in a subset of registries with good ascertainment. The prevalence was stable over time, but regional differences were observed. There were 145 (75.9%) terminations of pregnancy after prenatal diagnosis, 13 (6.8%) fetal deaths, 33 (17.3%) live births. In addition to cystic kidneys (97.7%), encephalocele (83.8%) and polydactyly (87.3%), frequent features include other central nervous system anomalies (51.4%), fibrotic/cystic changes of the liver (65.5% of cases with post mortem examination) and orofacial clefts (31.8%). Various other anomalies were present in 64 (37%) patients. As nowadays most patients are detected very early in pregnancy when liver or kidney changes may not yet be developed or may be difficult to assess, none of the anomalies should be considered obligatory for the diagnosis. Most cases (90.2%) are diagnosed prenatally at 14.3±2.6 (range 11-36) gestational weeks and pregnancies are mainly terminated, reducing the number of LB to one-fifth of the total prevalence rate. Early diagnosis is important for timely counseling of affected couples regarding the option of pregnancy termination and prenatal genetic testing in future pregnancies.

Novel biomarkers to predict response and prognosis in localized bladder cancer.

This review summarizes recent developments in diagnostic and prognostic biomarkers for nonmuscle invasive bladder cancer (NMIBC). Although the number of new biomarkers increases continuously, none are included in practice guidelines. Most NMIBC biomarkers show a higher sensitivity than urinary cytology, but lower specificity. Some protein and chromosome markers have been approved for screening and follow-up of patients in combination with cystoscopy. The long interval required for validation, testing, and approval of the assays and the lack of standardization could explain present issues in biomarker research. To enhance the development of new biomarkers, a more structured approach is required.

Five-year outcome of catheter ablation of persistent atrial fibrillation using termination of atrial fibrillation as a procedural endpoint.

BACKGROUND: This study aimed to determine 5-year efficacy of catheter ablation for persistent atrial fibrillation (AF) using AF termination as a procedural end point. METHODS AND RESULTS: One hundred fifty patients (57±10 years) underwent persistent AF ablation using a stepwise ablation approach (pulmonary vein isolation, electrogram-guided, and linear ablation) with the desired procedural end point being AF termination. Repeat ablation was performed for recurrent AF or atrial tachycardia. AF was terminated by ablation in 120 patients (80%). Arrhythmia-free survival rates after a single procedure were 35.3%±3.9%, 28.0%±3.7%, and 16.8%±3.2% at 1, 2, and 5 years, respectively. Arrhythmia-free survival rates after the last procedure (mean 2.1±1.0 procedures) were 89.7%±2.5%, 79.8%±3.4%, and 62.9%±4.5%, at 1, 2, and 5 years, respectively. During a median follow-up of 58 (interquartile range, 43-73) months after the last ablation procedure, 97 of 150 (64.7%) patients remained in sinus rhythm without antiarrhythmic drugs. Another 14 (9.3%) patients maintained sinus rhythm after reinitiation of antiarrhythmic drugs, and an additional 15 (10.0%) patients regressed to paroxysmal recurrences only. Failure to terminate AF during the index procedure (hazard ratio 3.831; 95% confidence interval, 2.070-7.143; P<0.001), left atrial diameter ≥50 mm (hazard ratio 2.083; 95% confidence interval, 1.078-4.016; P=0.03), continuous AF duration ≥18 months (hazard ratio 1.984; 95% confidence interval, 1.024-3.846; P<0.04), and structural heart disease (hazard ratio 1.874; 95% confidence interval, 1.037-3.388; P=0.04) predicted arrhythmia recurrence. CONCLUSIONS: In patients with persistent AF, an ablation strategy aiming at AF termination is associated with freedom from arrhythmia recurrence in the majority of patients over a 5-year follow-up period. Procedural AF nontermination and specific baseline factors predict long-term outcome after ablation.

Survival after surgical drainage of malignant pericardial effusion.

OBJECTIVES: Management of malignant pericardial effusion (PE) is complex. Cardiac surgeons are not necessarily familiar with or are challenged by the many underlying etiologies. Analyzing risk factors for mortality may help to estimate the benefit of surgery in high-risk patients. METHODS: Patients undergoing a surgical pericardiotomy for malignant PE, between 2001 and 2011, were included. The influence of tumor type, disease extension, intra-pericardial tumor infiltration on early mortality and long-term survival as well as freedom from symptoms after drainage, and the use of sclerosing agents on PE recurrence rates was analyzed. RESULTS: PE drainage was performed on 46 patients 12 ± 30 months after tumor diagnosis. Malignant diseases were lung cancers (50 %), breast cancers (15 %), lymphoma and leukemia (13 %), cancers of the digestive tract (13 %), and others (9 %). 80 % of patients were symptomatic and symptom relief was achieved in 65 %. Nobody died during surgery. Recurrence rate was 4 %. Early in-hospital mortality was 22 %. After 1 year, 29 % of patients were alive. Eleven patients (24 %) had a complete tumor regression. Metastatic spread (p < 0.001), pericardial infiltration (p = 0.02), and intra-pericardial Bleomycin (p = 0.01) injection were associated with increased mortality. Hematological malignancies had a better prognosis for survival. CONCLUSION: Surgical pericardiotomy is safe, associated with a low recurrence rate and symptom relief in the majority of dyspneic patients. Intra-pericardial Bleomycin may reduce recurrent effusion but does not ameliorate survival. Long-term survival rate was low with an increased mortality in cases of metastatic spreading, pericardial infiltration, and as the tumor of origin: breast cancers. Leukemic and lymphatic tumors have better prognosis.

External assessment of the Early Mortality Risk Score in patients with adenocarcinoma undergoing pancreaticoduodenectomy.

BACKGROUND: Pancreaticoduodenectomies (PD) still have a substantial mortality rate. Recently, different scores have been published to predict the mortality risk pre-operatively after PD. This retrospective study was designed to perform an external assessment of an Early Mortality Risk Score (EMRS). METHODS: From 2000 to 2012, all PD cases performed at our institution were documented. Only patients treated for pancreatic head adenocarcinomas were included. Survival time and EMRS (based on age, tumour size, tumour differentiation and comorbidities) were calculated for every patient. Relative risks (RR) of early death 9 and 12 months after PD were then calculated. RESULTS: Of 270 PD for various aetiologies, 120 PD for adenocarcinomas were included. The median follow-up was 37 months, and the overall median survival was 19 months. EMRS of 4 showed a mortality RR of 5.1 at 9 months (P = 0.048) and of 4.5 at 12 months (P = 0.020). CONCLUSIONS: EMRS of 4 is a predictor of tumour-related mortality at 9 and 12 months after PD for adenocarcinoma. The EMRS was externally assessed in our patient cohort and can be implemented in clinical practice. Clinical implications of this score still need to be studied.

Different Effects of BORIS/CTCFL on Stemness Gene Expression, Sphere Formation and Cell Survival in Epithelial Cancer Stem Cells.

Cancer stem cells are cancer cells characterized by stem cell properties and represent a small population of tumor cells that drives tumor development, progression, metastasis and drug resistance. To date, the molecular mechanisms that generate and regulate cancer stem cells are not well defined. BORIS (Brother of Regulator of Imprinted Sites) or CTCFL (CTCF-like) is a DNA-binding protein that is expressed in normal tissues only in germ cells and is re-activated in tumors. Recent evidences have highlighted the correlation of BORIS/CTCFL expression with poor overall survival of different cancer patients. We have previously shown an association of BORIS-expressing cells with stemness gene expression in embryonic cancer cells. Here, we studied the role of BORIS in epithelial tumor cells. Using BORIS-molecular beacon that was already validated, we were able to show the presence of BORIS mRNA in cancer stem cell-enriched populations (side population and spheres) of cervical, colon and breast tumor cells. BORIS silencing studies showed a decrease of sphere formation capacity in breast and colon tumor cells. Importantly, BORIS-silencing led to down-regulation of hTERT, stem cell (NANOG, OCT4, SOX2 and BMI1) and cancer stem cell markers (ABCG2, CD44 and ALDH1) genes. Conversely, BORIS-induction led to up-regulation of the same genes. These phenotypes were observed in cervical, colon and invasive breast tumor cells. However, a completely different behavior was observed in the non-invasive breast tumor cells (MCF7). Indeed, these cells acquired an epithelial mesenchymal transition phenotype after BORIS silencing. Our results demonstrate that BORIS is associated with cancer stem cell-enriched populations of several epithelial tumor cells and the different phenotypes depend on the origin of tumor cells.