Reprogramming energy metabolism and inducing angiogenesis : co-expression of monocarboxylate transporters with VEGF family members in cervical adenocarcinomas

Reprogramming energy metabolism and inducing angiogenesis: co-expression of monocarboxylate transporters with VEGF family members in cervical adenocarcinomas.

Neoplastic pericardial disease. Analysis of 26 patients

PURPOSE: To characterize patients with neoplastic pericardial disease diagnosed by clinical presentation, complementary test findings, and the histological type of tumor. METHODS: Twenty-six patients with neoplastic pericardial disease were retrospectively analyzed. RESULTS: Clinical manifestations and abnormalities in chest roentgenograms and electrocardiograms were frequent, but were not specific. Most patients underwent surgery. There was a high positivity of the pericardial biopsy when associated with the cytological analysis of the pericardial liquid used to determine the histological type of the tumor, particularly when the procedure was performed with the aid of pericardioscopy. CONCLUSION: The correct diagnosis of neoplastic pericardial disease involves suspicious but nonspecific findings during clinical examination and in screen tests. The suspicious findings must be confirmed through more invasive diagnostic approaches, in particular pericardioscopy with biopsy and cytological study.

The role of macroH2A1 in prostate carcinogenesis

Dissertação de mestrado em Genética Molecular

Candida tropicalis biofilms: biomass, metabolic activity and secreted aspartyl proteinase production

According to epidemiological data, Candida tropicalis has been related to urinary tract infections and haematological malignancy. Several virulence factors seem to be responsible for C. tropicalis infections, for example: their ability to adhere and to form biofilms onto different indwelling medical devices; their capacity to adhere, invade and damage host human tissues due to enzymes production such as proteinases. The main aim of this work was to study the behaviour of C. tropicalis biofilms of different ages (24120 h) formed in artificial urine (AU) and their ability to express aspartyl proteinase (SAPT) genes. The reference strain C. tropicalis ATCC 750 and two C. tropicalis isolates from urine were used. Biofilms were evaluated in terms of culturable cells by colony-forming units enumeration; total biofilm biomass was evaluated using the crystal violet staining method; metabolic activity was evaluated by XTT assay; and SAPT gene expression was determined by real-time PCR. All strains of C. tropicalis were able to form biofilms in AU, although with differences between strains. Candida tropicalis biofilms showed a decrease in terms of the number of culturable cells from 48 to 72 h. Generally, SAPT3 was highly expressed. C. tropicalis strains assayed were able to form biofilms in the presence of AU although in a strain- and time-dependent way, and SAPT genes are expressed during C. tropicalis biofilm formation.

Factors associated with the donation and non-donation of embryos for research: a systematic review

Background: Systematic knowledge on the factors that influence the decisions of IVF users regarding embryo donation for research is a core need for patient-centred policies and ethics in clinical practice. However, no systematic review has been provided on the motivations of patients who must decide embryo disposition. This paper fills this gap, presenting a systematic review of quantitative and qualitative studies, which synthesizes the current body of knowledge on the factors and reasons associated with IVF patients’ decisions to donate or not to donate embryos for research. Methods: A systematic search of studies indexed in PubMed, ISIWoK and PsycINFO, published before November 2013, was conducted. Only empirical, peer-reviewed, full-length, original studies reporting data on factors and reasons associated with the decision concerning donation or non-donation of embryos for research were included. Eligibility and data extraction were performed by two independent researchers and disagreements were resolved by discussion or a third reviewer, if required. The main quantitative findings were extracted and synthesized and qualitative data were assessed by thematic content analysis. Results: A total of 39 studies met the inclusion criteria and were included in the review. More than half of the studies (n ¼ 21) used a quantitative methodology, and the remaining were qualitative (n ¼ 15) or mixed-methods (n ¼ 3) studies. The studies were derived mainly from European countries (n ¼ 18) and the USA(n ¼ 11). The proportion of IVF users who donated embryos for research varied from 7% in a study in France to 73% in a Swiss study. Those who donate embryos for research reported feelings of reciprocity towards science and medicine, positive views of research and high levels of trust in the medical system. They described their decision as better than the destruction of embryos and as an opportunity to help others or to improve health and IVF treatments. The perception of risks, the lack of information concerning research projects and the medical system and the conceptualization of embryos in terms of personhood were the most relevant motives for not donating embryos for research. Results relating to the influence of sociodemographic characteristics and reproductive and gynaecological history were mostly inconclusive. Conclusions: Three iterative and dynamic dimensions of the IVF patients’ decision to donate or not to donate embryos for research emerged from this review: the hierarquization of the possible options regarding embryo disposition, according to the moral, social and instrumental status attributed to embryos; patients’ understanding of expectations and risks of the research on human embryos; and patients’ experiences of information exchange and levels of trust in the medical-scientific institutions.

Utentes da Consulta Externa de Ginecologia/Obstetrícia da Maternidade Júlio Dinis

Com o objectivo de fazer a caracterização da situação social e demográfica e das condições de saúde médica e psicológica das utentes da Consulta Externa de Ginecologia/Obstretícia da Maternidade Júlio Dinis e de seus companheiros, duzentas mulheres e cento e setenta e cinco homens (N=375) foram entrevistados com base num questionário desenhado para o efeito, durante o primeiro trimestre de gestação. Observamos o desfavorecimento social e económico da amostra, particularmente no grupo das mulheres. Constatamos que a situação matrimonial e familiar é estável; no entanto, muitos agregados familiares são recentes, incluem outros familiares e este é um primeiro filho do casal. A rede de apoio social e emocional da amostra é geralmente constituída por familiares, estando mais presente para as mulheres do que para os homens e muitas vezes o companheiro não é referido como confidente, sobretudo pelas mulheres. A gestação não é geralmente de risco; não obstante, a presença frequente de problemas psicológicos uma pior aceitação inicial da gravidez no caso das mulheres. Os hábitos de vida tornam-se mais saudáveis com a gestação; no entanto, é ainda elevado o consumo de substâncias, como o tabaco, pela grávida. Problemas ginecológicos e obstétricos foram referidos, assim como a presença de adversidades na história psicológica e desenvolvimental dos participantes. Concluímos que as utentes da Consulta Externa de Ginecologia/Obstetrícia da Maternidade Júlio Dinis e seus companheiros apresentam indicadores relevantes de risco médico, psicológico e social que devem ser considerados na prestação de melhores cuidados de saúde.

Interacciones inmuno-endócrinas: participación de tlr-4 y citoquinas pro-inflamatorias en la regulación de la proliferación de células lactotropas. Immuno-endocrine interactions: Contribution of tlr-4 and pro-inflammatory cytokines in the regulation of lactotroph cell proliferation.

El presente proyecto tiene como objetivo estudiar, a nivel celular y molecular, los mecanismos inmuno-endócrinos que participan en la proliferación de células lactotropas normales y tumorales frente a procesos inflamatorios inducidos experimentalmente. Una particular atención se pondrá al evaluar la contribución de IL-6 como citoquina intrahipofisaria durante el desarrollo tumoral y su rol como señal paracrina/autocrina en la senescencia hipofisaria. Debido a que agentes inflamatorios y anti-inflamatorios pueden inducir alteraciones en el crecimiento y la función hipofisaria, no se descartaría que, en el curso de una inflamación, como la inducida por el lipopolisacárido bacteriano LPS, puedan ocurrir modificaciones en el índice proliferativo de las células lactotropas y/o en la secreción de su producto hormonal, la prolactina. Dado el auge en las investigaciones referidas al campo de la modulación inmuno-endócrina, es que planteamos investigar la participación de TLR4, componente crucial del complejo proteico que inicia la señal LPS, en hipófisis normales y tumorales inducidas por estrógeno así como también en la línea celular somatolactotrópica GH3B6. Dentro de las vías de transducción de señales involucradas se determinará la participación de MAPK-ERK1/2 y de PI3K asi como la contribución de NF-kB en la regulación del crecimiento celular inducido por IL-6/LPS mediante el uso de inhibidores específicos. La microscopía electrónica y confocal, resultarán de fundamental importancia para valorar los procesos de translocación nuclear de NF-kB como así también para definir la localización ultraestructural de los mediadores mencionados. Además, se valorará el mecanismo de senescencia celular hipofisaria mediante parámetros morfológicos, bioquímicos y ultraestructurales durante el desarrollo de prolactinomas inducidos experimentalmente. Finalmente dilucidar las posibles vías de transducción de señales que se desencadenan frente a estímulos inflamatorios/proliferativos podría explicar algunos aspectos moleculares sobre la función de control del ciclo celular y las limitaciones de crecimiento en adenomas hipofisarios que subyacen en la falta de progresión de estos tumores a la malignidad. The aim of the present project is to study the immuno-endocrine mechanisms involved in the proliferation of normal and tumoral lactotrophs experimentally induced by inflammatory factors. Also, the contribution of IL-6 as a paracrine / autocrine signal in the pituitary senescence will be assessed along tumor development induced by estrogen treatment. Considering that both, inflammatory and anti-inflammatory agents can modify the pituitary function, it is possible that in the course of inflammation, as induced by bacterial lipopolysaccharide LPS, some alteration may occur in the proliferative index of lactotrophs and / or in the PRL secretion. Our main objective is to investigate the cellular and molecular mechanisms involved by the activation of TLR4, a crucial component of the protein complex initiated by LPS, in normal and pathological pituitaries induced by estrogen as well as in the GH3B6 cell line. The participation of MAPK-ERK1 / 2 and PI3K signaling pathway and the contribution of NF-kB in the proliferative responses triggered by IL-6/LPS will be analyzed by using specific inhibitors. Confocal microscopy analysis is essential to assess the process of nuclear translocation of NF-kB as well as the use of electron microscopy to define the ultrastructural localization of the above mentioned mediators. In addition, the mechanisms of pituitary cell senescence will be evaluated through morphological, biochemical and ultrastructural approaches during the development of experimental prolactinomas. Finally, the elucidation of possible signal transduction pathways which are triggered by inflammatory / proliferative stimuli, would explain some molecular aspects of cell cycle control and limitations in pituitary tumor growth that underlie the lack of progress in these pituitary tumors to malignancy.

Prise en charge des cancers du cavum (rhinopharynx) Nasopharyngeal cancers, an overview.

Les cancers du cavum ont une incidence d'environ 0,5 cas par an et par 100 000 habitants pour les hommes en France, mais sont endémiques dans des régions comme l'Asie du Sud-Est. La prise en charge thérapeutique par radiothérapie exclusive, qui a longtemps été le standard, permet d'obtenir des taux de contrôle local pour les stades T3-T4 de l'ordre de 50 à 75 % des cas. Les techniques d'irradiation en modulation d'intensité permettent une excellente couverture dosimétrique avec une meilleure protection des organes à risque et doivent être privilégiées. L'apport d'une chimiothérapie concomitante à l'IMRT améliore significativement les taux de survie globale qui sont supérieurs ou égaux à 75 % à cinq ans dans les stades avancés. Dans la pratique courante, une radiochimiothérapie concomitante à base de sels de platine est réalisée mais la place des cures néoadjuvantes et/ou adjuvantes est discutée dans le but principal de diminuer les rechutes à distance, des études sont en cours. Enfin, la surveillance doit être axée sur la détection précoce de rechutes locales potentiellement curables et sur la prise en charge des séquelles thérapeutiques à long terme. Cancer of the nasopharynx is an uncommon malignancy in France (incidence = 0.5/year/100,000 men) but is endemic in areas like in South-East Asia. Exclusive radiation therapy used to be the standard and results in local control rates for T3-T4 tumors around 50-75 %. Intensity-modulated radiotherapy (IMRT) improves tumor coverage with a sparing of organs at risk and has to be privileged. Concurrent chemotherapy with IMRT achieved significant survival benefice with 5-year overall survival above 75 %. Concurrent radiochemotherapy with platinium is the most frequent scheme but induction and adjuvant chemotherapies are discussed to reduce distant failure: studies are currently ongoing. Follow-up aims to detect early local failures with a chance of cure and to manage long-term toxicities.

Development of Ewing's sarcoma from primary bone marrow-derived mesenchymal stem cells

SUMMARY : Ewing's sarcoma is a member of Ewing's family tumors (ESPY) and the second most common solid bone and soft tissue malignancy of children and young adults. It is associated in 85% of cases with the t(11;22)(q24:q12) chromosomal translocation that generates fusion of the 5' segment of the EWSR1 gene with the 3' segment of the ETS family gene FLI-1. The EWSR1-FLI-1 fusion protein behaves as an aberrant transcriptional activator and is believed to contribute to ESFT development. However, EWSR1-FLI-1 induces growth arrest and apoptosis in normal fibroblasts, and primary cells that are pemissive for its putative oncogenic properties have not been discovered, hampering basic understanding of ESFT biology. Here, we show that EWSR1-FLI-1 alone can transform mouse primary bone marrow-derived mesenchymal progenitor cells and generate tumors that display hallmarks of Ewing's sarcoma, including a small round cell phenotype, expression of ESFT-associated markers, insulin like growth factor-I dependence, and induction or repression of numerous EWSR1-FLI-1 target genes. Consistent with this finding, we tested the possibility that human mesenchymal stem cells (hMSC) might also provide a permissive cellular environment for EWSR1-FLI-1, and could represent the first adequate primary human cellular background for the oncogenic properties of the fusion protein. Indeed, expression of EWSR1-FLI-1 in human mesenchymal stem cells (hMSC) was not only stably maintained without inhibiting proliferation, but induced a gene expression profile bearing striking similarity to that of ESFT, including genes that are among the highest ESFT discriminators. Expression of EWSR1-FLI-1 in hMSCs may recapitulate the initial steps of Ewing's sarcoma development, allowing identification of genes that play an important role early in its pathogenesis. Among relevant candidate transcripts induced by EWSR1-FL/-1 in hMSC we found the polycomb group gene EZH2 which we show to play a critical role in Ewing's sarcoma growth. These observations provide the first identification of candidate primary cells from which ESFTs originate and suggest that EWSR1-FLI-1 expression may constitute the initiating event in ESFT pathogenesis. Le sarcome d' Ewing est un membre de la famille des tumeurs Ewing (ESFT) et représente la deuxième tumeur maligne solide de l'os et des tissus mous chez les enfants et les jeunes adultes. Cette tumeur est associée dans 85% des cas avec la translocation chromosomique t(11;22)(g24:g12), qui génère la fusion entre le segment 5' du gène EWSR1 avec le segment 3' du gène FLI-1, appartenant à la famille des facteurs de transcription ETS. La protéine de fusion EWSR1-FLI-1 qui en dérive joue le rSle d'un facteur de transcription aberrant, et est supposée contribuer de manière décisive au processus de développement des ESFTs. Néanmoins, l'expression de EWSR1-FLI-1 dans des fibroblastes normaux induit un arrêt de croissance et leur apoptose, et les cellules primaires permissives pour les propriétés oncogéniques attribuées à la translocation n'ont pas encore été identifiées, empêchant la compréhension de la biologie de base du sarcome d'Ewing. Dans ce travail on montre que l'expression de EWSR1-FLI-1 uniquement est capable de transformer des cellules souches mésenchymateuses dérivées de la moelle osseuse de la souris, pour générer des tumeurs qui présentent les caractéristiques du sarcome d' Ewing humain, et notamment une morphologie de petites cellules bleues et rondes, l'expression de marqueurs associés aux ESFTs, une dépendance du facteur de croissance IGF-1, et l'induction ou la répression de nombreux gènes cibles connus de EWSR1-FLI-1. Sur la base de ces observations, on a testé la possibilité que les cellules souches mésenchymateuses humaines (hMSCs) puissent aussi fournir un environnement cellulaire permissif pour EWSR1-FLI-1 ; et représenter le premier background cellulaire humain adéquat pour la manifestation du pouvoir oncogénique de la protéine de fusion. En effet, l'expression de EWSR1-FLI-1 dans des cellules souches mésenchymateuses humaines s'est révélée non seulement maintenue, mais elle a induit un profil d'expression génétique étonnamment similaire à celui des ESFTs humains, incluant les gènes qui ont été rapportés comme étant les plus discriminatifs pour ces tumeurs. L'expression de EWSR1-FLI-1 dans les hMSCs pourrait récapituler les étapes initiales du développement du sarcome d' Ewing, et de ce fait consentir à identifier les gènes qui jouent un rôle crucial dans sa pathogenèse précoce. Parmi les transcrits relevant indults par EWSR1-FL/-9 dans les hMSCs nous avons découvert le gène du groupe des polycomb EZH2, que nous avons par la suite démontré jouer un rôle essentiel dans la croissance du sarcome de Ewing. Ces observations apportent pour la première fois l'identification d'une cellule primaire candidate pour représenter la cellule d'origine des ESFTs, et en même temps suggèrent que l'expression de EWSR1-FLI-1 peut constituer l'événement initial dans la pathogenèse du sarcome d' Ewing.

Tolerance-inducing immunosuppressive strategies in clinical transplantation: an overview.

The significant development of immunosuppressive drug therapies within the past 20 years has had a major impact on the outcome of clinical solid organ transplantation, mainly by decreasing the incidence of acute rejection episodes and improving short-term patient and graft survival. However, long-term results remain relatively disappointing because of chronic allograft dysfunction and patient morbidity or mortality, which is often related to the adverse effects of immunosuppressive treatment. Thus, the induction of specific immunological tolerance of the recipient towards the allograft remains an important objective in transplantation. In this article, we first briefly describe the mechanisms of allograft rejection and immune tolerance. We then review in detail current tolerogenic strategies that could promote central or peripheral tolerance, highlighting the promises as well as the remaining challenges in clinical transplantation. The induction of haematopoietic mixed chimerism could be an approach to induce robust central tolerance, and we describe recent encouraging reports of end-stage kidney disease patients, without concomitant malignancy, who have undergone combined bone marrow and kidney transplantation. We discuss current studies suggesting that, while promoting peripheral transplantation tolerance in preclinical models, induction protocols based on lymphocyte depletion (polyclonal antithymocyte globulins, alemtuzumab) or co-stimulatory blockade (belatacept) should, at the current stage, be considered more as drug-minimization rather than tolerance-inducing strategies. Thus, a better understanding of the mechanisms that promote peripheral tolerance has led to newer approaches and the investigation of individualized donor-specific cellular therapies based on manipulated recipient regulatory T cells.

Increased plasticity of the stiffness of melanoma cells correlates with their acquisition of metastatic properties.

The stiffness of tumor cells varies during cancer progression. In particular, metastatic carcinoma cells analyzed by Atomic Force Microscopy (AFM) appear softer than non-invasive and normal cells. Here we examined by AFM how the stiffness of melanoma cells varies during progression from non-invasive Radial Growth Phase (RGP) to invasive Vertical Growth Phase (VGP) and to metastatic tumors. We show that transformation of melanocytes to RGP and to VGP cells is characterized by decreased cell stiffness. However, further progression to metastatic melanoma is accompanied by increased cell stiffness and the acquisition of higher plasticity by tumor cells, which is manifested by their ability to greatly augment or reduce their stiffness in response to diverse adhesion conditions. We conclude that increased plasticity, rather than decreased stiffness as suggested for other tumor types, is a marker of melanoma malignancy. These findings advise caution about the potential use of AFM for melanoma diagnosis. FROM THE CLINICAL EDITOR: This study investigates the changes to cellular stiffness in metastatic melanoma cells examined via atomic force microscopy. The results demonstrate that increased plasticity is a marker of melanoma malignancy, as opposed to decreased stiffness.

Prevalence of human papillomavirus DNA in female cervical lesions from Rio de Janeiro, Brazil

A hundred-sixty paraffin-embedded specimens from female cervical lesions were examined for human papillomavirus (HPV) types 6, 11, 16 and 18 infections by non-isotopic in situ hybridization. The data were compared with histologic diagnosis. Eighty-eight (55) biopsies contained HPV DNA sequences. In low grade cervical intraepithelial neoplasias (CIN I), HPV infection was detected in 78.7 of the cases, the benign HPV 6 was the most prevalent type. HPV DNA was detected in 58 of CIN II and CIN III cases and in 41.8 of squamous cell carcinomas (SCC). Histologically normal women presented 20 of HPV infection. Oncogenic HPV was found in 10 of these cases, what may indicate a higher risk of developing CINs and cancer. Twenty-five percent of the infected tissues contained mixed infections. HPV 16 was the most common type infecting the cervix and its prevalence raised significantly with the severity of the lesions, pointing its role in cancer pathogenesis. White women presented twice the cervical lesions of mulatto and African origin women, although HPV infection rates were nearly the same for the three groups (approximately 50). Our results showed that HPV typing by in situ hybridization is a useful tool for distinguishing between low and high risk cervical lesions. Further studies are required to elucidate risk factors associated with HPV infection and progression to malignancy in Brazilian population.

Rekonstruktion von Oberkieferdefekten mit einem freien Skapula-angle-Lappen [Reconstruction of maxillary defects using a free scapular angle flap].

BACKGROUND: In addition to prosthetic rehabilitation, maxillary defects can also be surgically reconstructed. Soft-tissue reconstruction employs a radial forearm or latissimus dorsi muscle flap, while bony reconstruction can be achieved using a fibula, iliac crest, or scapular flap. Reconstruction using a scapular flap is further divided into two subgroups: the traditional scapular flap with the circumflex scapular artery as the donor vessel and the scapular angle flap with the angular artery originating from the thoracodorsal artery as the donor vessel. MATERIALS AND METHODS: We report on four patients who underwent successful reconstruction with a free scapular angle flap between 2009 and 2011, following maxillary resection due to malignancy. RESULTS: Vertical positioning of the scapular angle flap enables reconstruction of the facial contour, whereas its horizontal alignment and microvascular anastomosis makes a bony reconstruction of the hard palate possible. CONCLUSIONS: The versatility, low rate of donor site morbidity and shape of the scapular angle flap--which resembles that of the hard palate--render it ideal for plastic reconstruction. The suitability of bone quality for dental rehabilitation with implants is a topic of controversial discussion. The scapular angle flap represents an alternative to obturator prosthesis for the reconstruction of maxillary defects ≥ grade I according to Okay et al.

Development of Ewing's sarcoma from primary bone marrow-derived mesenchymal progenitor cells.

Ewing's sarcoma is a member of Ewing's family tumors (EFTs) and the second most common solid bone and soft tissue malignancy of children and young adults. It is associated in 85% of cases with the t(11;22)(q24:q12) chromosomal translocation that generates fusion of the 5' segment of the EWS gene with the 3' segment of the ETS family gene FLI-1. The EWS-FLI-1 fusion protein behaves as an aberrant transcriptional activator and is believed to contribute to EFT development. However, EWS-FLI-1 induces growth arrest and apoptosis in normal fibroblasts, and primary cells that are permissive for its putative oncogenic properties have not been discovered, hampering basic understanding of EFT biology. Here, we show that EWS-FLI-1 alone can transform primary bone marrow-derived mesenchymal progenitor cells and generate tumors that display hallmarks of Ewing's sarcoma, including a small round cell phenotype, expression of EFT-associated markers, insulin like growth factor-I dependence, and induction or repression of numerous EWS-FLI-1 target genes. These observations provide the first identification of candidate primary cells from which EFTs originate and suggest that EWS-FLI-1 expression may constitute the initiating event in EFT pathogenesis.

Identification of cancer stem cells in Ewing's sarcoma

Summary : Cancer stem cells (CSC) that display tumor-initiating properties have recently been identified in several distinct types of malignancies, holding promise for more effective therapeutic strategies. However, evidence of such cells in sarcomas, which include some of the most aggressive and therapy-resistant tumors, has not been demonstrated to date. Here, we .identify and characterize cancer stem cells in Ewing's sarcoma family tumors (ESPY), a highly aggressive pediatric malignancy believed to be of mesenchymal stem cell (MSC) origin. Using magnetic bead cell separation of primary ESFT, we have isolated a subpopulation of CD133+ tumor cells that display the capacity to initiate and sustain tumor growth through serial transplantation in NOD/SCID mice, re-establishing at each in vivo passage the parental tumor phenotype and hierarchical cell organization. Consistent with the plasticity of MSCs, in vitro differentiation assays showed that the CD133+ cell population retained the ability to differentiate along adipogenic, osteogenic and chondrogenic lineages. Quantitative Real-Time PCR analysis of genes implicated in stem cell maintenance revealed that CD133+ ESFT cells express significantly higher levels of OCT4 and NANOG than their CD133- counterparts. Taken together, our observations provide the first identification of ESFT cancer stem cells (ET-CSC) and demonstration of their mesenchymal stem cell properties, a critical step toward a better biological understanding and rational therapeutic targeting of these tumors. Résumé : Des cellules souches tumorales avec des propriétés exclusives d'initiation tumorale ont récemment été identifiées dans différents types de cancers, permettant ainsi d'espérer le développement de thérapies plus efficaces. Cependant, l'existence de telles cellules dans les sarcomes, un sous-groupe de cancers d'origine mésenchymateuse très agressifs, n'a pas encore été démontrée. Dans ce travail de recherche, nous identifions et caractérisons des cellules souches tumorales dans le sarcome d'Ewing, une tumeur pédiatrique très agressive vraisemblablement dérivée de cellules souches mésenchymateuses (MSC). Afin de séparer des populations cellulaires dans des échantillons primaires de sarcome d'Ewing, nous avons utilisé des billes magnétiques couplées à des anticorps monoclonaux. Ceci nous a permis d'isoler une sous-population de cellules tumorales CD133+ qui ont la capacité d'initier et de maintenir la croissance tumorale dans des xénotransplantations en série effectuées dans des souris immunodéficientes NOD/SCID. Ces cellules reétablissent à chaque passage in vivo le phénotype de la tumeur d'origine ainsi que son organisation hiérarchique. En accord avec la plasticité des MSC, des tests de différentiation in vitro ont montré que les cellules CD133+ maintiennent la capacité de se différentier en adipocytes, ostéocytes et chondrocytes. Une analyse par PCR quantitative de gènes impliqués dans le maintien des cellules souches a montré que les cellules CD133+ expriment un niveau beaucoup plus élevé de OCT4 and NANOG que les cellules CD133-. En résumé, nos observations constituent la première identification de cellules souches tumorales dans le sarcome d'Ewing et démontrent leur propriété de cellules souches mésenchymateuses. Ceci constitue une étape clé vers une meilleure compréhension biologique et une meilleure approche thérapeutique de ces tumeurs.