Search

Comment in Discussion: Opposite Effects of Soluble Factors Secreted by Adipose Tissue on Proliferating and Quiescent Osteosarcoma Cells. [Plast Reconstr Surg. 2016]; International audience; BACKGROUND:Autologous adipose tissue transfer may be performed for aesthetic needs following resection of osteosarcoma, the most frequent primary malignant tumor of bone, excluding myeloma. The safety of autologous adipose tissue transfer regarding the potential risk of cancer recurrence must be addressed.METHODS:Adipose tissue injection was tested in a human osteosarcoma preclinical model induced by MNNG-HOS cells. Culture media without growth factors from fetal bovine serum were conditioned with adipose tissue samples and added to two osteosarcoma cell lines (MNNG-HOS and MG-63) that were cultured in monolayer or maintained in nonadherent spheres, favoring a proliferation or quiescent stage, respectively. Proliferation and cell cycle were analyzed.RESULTS:Adipose tissue injection increased local growth of osteosarcoma in mice but was not associated with aggravation of lung metastasis or osteolysis. Adipose tissue-derived soluble factors increased the in vitro proliferation of osteosarcoma cells up to 180 percent. Interleukin-6 and leptin were measured in higher concentrations in adipose tissue-conditioned medium than in osteosarcoma cell-conditioned medium, but the authors' results indicated that they were not implicated alone. Furthermore, adipose tissue-derived soluble factors did not favor a G0-to-G1 phase transition of MNNG-HOS cells in nonadherent oncospheres.CONCLUSIONS:This study indicates that adipose tissue-soluble factors activate osteosarcoma cell cycle from G1 to mitosis phases, but do not promote the transition from quiescent G0 to G1 phases. Autologous adipose tissue transfer may not be involved in the activation of dormant tumor cells or cancer stem cells.

Conventional therapy of primary bone tumors includes surgical excision with wide resection, which leads to physical and aesthetic defects. For reconstruction of bone and joints, allografts can be supplemented with mesenchymal stem cells (MSCs). Similarly, adipose tissue transfer (ATT) is supplemented with adipose-derived stem cells (ADSCs) to improve the efficient grafting in the correction of soft tissue defects. MSC-like cells may also be used in tumor-targeted cell therapy. However, MSC may have adverse effects on sarcoma development. In the present study, human ADSCs, MSCs and pre-osteoclasts were co-injected with human MNNG-HOS osteosarcoma cells in immunodeficient mice. ADSCs and MSCs, but not the osteoclast precursors, accelerated the local proliferation of MNNG-HOS osteosarcoma cells. However, the osteolysis and the metastasis process were not exacerbated by ADSCs, MSCs, or pre-osteoclasts. In vitro proliferation of MNNG-HOS and Saos-2 osteosarcoma cells was increased up to 2-fold in the presence of ADSC-conditioned medium. In contrast, ADSC-conditioned medium did not change the dormant, quiescent state of osteosarcoma cells cultured in oncospheres. Due to the enhancing effect of ADSCs/MSCs on in vivo/in vitro proliferation of osteosarcoma cells, MSCs may not be good candidates for osteosarcoma-targeted cell therapy. Although conditioned medium of ADSCs accelerated the cell cycle of proliferating osteosarcoma cells, it did not change the quiescent state of dormant osteosarcoma cells, indicating that ADSC-secreted factors may not be involved in the risk of local recurrence., Graphical abstract fx1

International audience; Humans are chronically exposed to multiple environmental pollutants such as pesticides with no significant evidence about the safety of such poly-exposures. We exposed mesenchymal stem cells (MSC) to very low doses of mixture of seven pesticides frequently detected in food samples for 21 days in vitro. We observed a permanent phenotype modification with a specific induction of an oxidative stress-related senescence. Pesticide mixture also induced a shift in MSC differentiation towards adipogenesis but did not initiate a tumorigenic transformation. In modified MSC in which a premalignant phenotype was induced, the exposure to pesticide mixture promoted tumorigenic phenotype both in vitro and in vivo after cell implantation, in all nude mice. Our results suggest that a common combination of pesticides can induce a premature ageing of adult MSC, and as such could accelerate age-related diseases. Exposure to pesticide mixture may also promote the tumorigenic transformation in a predisposed stromal environment. STEM CELLS 2017;35:800-811 SIGNIFICANCE STATEMENT The environmental exposure to pesticides is recognized as a potential threat to human health. However, little is known on the effect of pesticides on stem cells. Here we show that a pesticide mixture, at doses commonly found in western diet, promotes stress-related senescence in normal MSC and tumorigenesis in premalignant MSC. Our results provide a new insight in the effect of pesticides on the acceleration of stem cell ageing and possibly on cancer.

Behjati et al recently described recurrent mutations of H3F3 genes in giant cell tumors of the bone and chondroblastomas. Both these entities belong to the spectrum of giant cell-rich bone lesions, often presenting a diagnostic challenge for the pathologist. Our aim was to investigate the value of searching for H3F3 mutations in the diagnosis of giant cell tumors of the bone and giant cell-rich chondroblastomas. Two hundred eighty-one bone lesion samples, including 170 giant cell tumors of the bone, 26 chondroblastomas and 85 other giant cell-rich and/or epiphyseal tumors, were analyzed. Mutation status was determined using first high resolution melting screening and then mutation profiling pyrosequencing. Mutational status was compared with clinical data and, for giant cell tumors of the bone, with p63 immunostaining status. As histone methylation changes have been reported in association with H3F3 mutations, the methylation status of lysine 37 was investigated. H3F3A and H3F3B were found in 85% of giant cell tumors of the bone and 88% of chondroblastomas. In addition to the major G35W mutation, we found two rare H3F3A mutations: one G35R and one G35V. Among the other tumors studied, we only found H3F3A gene mutations in two cases of 'dedifferentiated chondrosarcoma mimicking giant cell tumor of the bone'. A H3F3B mutation was also observed in one case of dedifferentiated chondroblastoma. P63 expression in giant cell tumors of the bone seems to be associated with H3F3 gene mutations (P=0.004). H3F3 mutations did not correlate with clinical data, outcome or methylation changes in Lysin 37. In conclusion, H3F3 mutations are sensitive and specific markers of giant cell tumors of the bone and chondroblastomas. High resolution melting and pyrosequencing procedures are high-performance tools in this context. Determination of H3F3 mutation will allow reclassification of some entities belonging to the spectrum of giant cell-rich lesions.

Compte tenu des donnees constitutionnelles et politiques de la Ve Republique que l’on tient pour acquises (sauf a remettre en cause le « parlementarisme negatif » qui caracterise cette derniere), le renforcement du Parlement peut etre cherche en combinant les deux clivages caracteristiques du regime : la distinction politique entre l’ensemble gouvernement-majorite et l’opposition d’une part, la separation institutionnelle de l’executif et du legislatif d’autre part. Si la fonction legislative, qui met en œuvre une politique, sera toujours exercee essentiellement par la majorite sous l’egide du gouvernement, en revanche la fonction de controle et d’evaluation dans son acception moderne est la vocation specifique de l’institution parlementaire, non de la seule opposition, et appelle des solutions innovantes. Il devrait en resulter un reequilibrage a son profit de l’activite et du fonctionnement des assemblees.

Apres qu'une session entiere s'est deroulee sous l'empire des nouvelles dispositions relatives a la procedure legislatives, il est possible de dresser un bilan provisoire de leur application. Les deux innovations principales concernent, d'une part, le partage de l'ordre du jour entre le Gouvernement et le Parlement, qui a donne lieu a une pratique differente au Senat et a l'Assemblee nationale, et, d'autre part, le role accru des commissions par rapport a la seance. Si le partage du temps, qui affecte l'initiative gouvernementale et beneficie essentiellement a la majorite, s'est opere au prix de certains amenagements, le reequilibrage souhaite entre la seance et le travail en commission cherche encore son regime de croisiere.

On peut soutenir que la pratique institutionnelle suivie depuis l'election de Nicolas Sarkozy a la presidence de la Republique est la consequence naturelle du quinquennat et de l'amenagement du calendrier electoral qui l'a complete - et donc la consequence des initiatives de Lionel Jospin a qui il serait d'autant plus equitable de rendre ce qui lui est du qu'il n'en a pas tire benefice. On peut aussi considerer que cette pratique prefigure une V e Republique bis, invoquee ici par Jean-Francois Cope (« Vers le regime presidentiel. Pour un Parlement renove », Commentaire, n° 129, printemps 2010, p. 51) - pour ne pas dire une VI e , laquelle est un peu defraichie, ayant tant servi depuis que Maurice Duverger annoncait en 1961: La VI e Republique et le regime presidentiel ! Sans aucun doute, la question ainsi renouvelee merite discussion ; elle appelle en tout cas un commentaire qui attire l'attention sur la meprise a laquelle expose une reponse hâtive. Ce commentaire se deroulera sur deux plans, repondant aux deux faces de la meprise encourue, qui est a la fois intellectuelle et concrete.

Une illusion domine notre histoire constitutionnelle depuis 1789, qui reprend a sa maniere le fameux titre d’Austin : Quand dire, c’est faire. Il s’en est suivi une succession d’enthousiasmes et de deceptions dont la Ve Republique fournit un condense instructif. Cette experience a d’abord ete une lecon de realisme constitutionnel en mettant en evidence la nature politique du droit qu’edictent les textes et les limites d’une approche exclusivement juridique. Inversement, si l’instauration d’un controle juridictionnel a fait progresser l’Etat de droit, sa pratique en a aussi revele les effets pervers avec la multiplication des revisions et la banalisation de la Constitution, qu’amplifie desormais la subordination a l’ordre europeen.