Low-diluted Phenacetinum disrupted the melanoma cancer cell migration

Dynamic and reciprocal interactions generated by the communication between tumor cells and their matrix microenvironment, play a major role in the progression of a tumor. Indeed, the adhesion of specific sites to matrix components, associated with the repeated and coordinated formation of membrane protrusions, allow tumor cells to move along a determined pathway. Our study analyzed the mechanism of action of low-diluted Phenacetinum on murine cutaneous melanoma process in a fibronectin matrix environment. We demonstrated a reduction of dispersed cell migration, early and for as long as 24 h, by altering the formation of cell protrusions. Moreover, low-diluted Phenacetinum decreased cell stiffness highly on peripheral areas, due to a disruption of actin filaments located just under the plasma membrane. Finally, it modified the structure of the plasma membrane by accumulating large ordered lipid domains and disrupted B16 cell migration by a likely shift in the balance between ordered and disordered lipid phases. Whereas the correlation between the excess of lipid raft and cytoskeleton disrupting is not as yet established, it is clear that low-diluted Phenacetinum acts on the actin cytoskeleton organization, as confirmed by a decrease of cell stiffness affecting ultimately the establishment of an effective migration process

ZO-1 Intracellular Localization Organizes Immune Response in Non-Small Cell Lung Cancer

International audienceDelocalization of zonula occludens-1 (ZO-1) from tight junctions plays a substantial role in epithelial cell plasticity observed during tumor progression. In vitro , we reported an impact of ZO-1 cyto-nuclear content in modulating the secretion of several pro-inflammatory chemokines. In vivo , we demonstrated that it promotes the recruitment of immune cells in mouse ear sponge assays. Examining lung cancers, we showed that a high density of CD8 cytotoxic T cells and Foxp3 immunosuppressive regulatory T cells in the tumor microenvironment correlated with a cyto-nuclear expression of ZO-1. Taken together, our results support that, by affecting tumor cell secretome, the cyto-nuclear ZO-1 pool may recruit immune cells, which could be permissive for tumor progression

Rôle du gène hNanos 1 dans le processus d'invasion tumorale

REIMS-BU Santé (514542104) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Dynamized ultra-low dilution of Ruta graveolens disrupts plasma membrane organization and decreases migration of melanoma cancer cell

ABSTRACTCutaneous melanoma is a cancer with a very poor prognosis mainly because of metastatic dissemination and therefore a deregulation of cell migration. Current therapies can benefit from complementary medicines as supportive care in oncology. In our study, we show that a dynamized ultra-low dilution of Ruta Graveolens leads to an in vitro inhibition of migration on fibronectin of B16F10 melanoma cells, as well as a decrease in metastatic dissemination in vivo. These effects appear to be due to a disruption of plasma membrane organization, with a change in cell and membrane stiffness, associated with a disorganization of the actin cytoskeleton and a modification of the lipid composition of the plasma membrane. Together, these results demonstrate, in in vitro and in vivo models of cutaneous melanoma, an anti-cancer and anti-metastatic activity of ultra-low dynamized dilution of Ruta graveolens and reinforce its interest as complementary medicine in oncology

Effect of saw blade geometry on crack initiation and propagation on the lateral cortical hinge for HTO: Finite element analysis.

Place: FranceInternational audienceINTRODUCTION: The hinge plays a primary role in the hold and healing of a high tibial osteotomy (HTO). Weakening of the hinge is a risk factor for failure. The aim of our study was to determine whether the geometry of the saw blade's cutting edge impacts crack initiation or propagation on the hinge. HYPOTHESIS: A certain cutting edge geometry exists that will reduce this risk. MATERIALS AND METHODS: A finite element model with transverse isotropic elastic bone properties was created. A 1.27-mm thick saw cut (full thickness in anteroposterior direction) was made leaving a 1cm lateral cortical hinge. Three different cutting edge geometries were compared: rectangular, U-shaped, V-shaped. Opening of the osteotomy was done over 1mm for 1 s by a load applied distally with the proximal portion fixed. In the first simulation, no crack was initiated at the hinge, while in the second simulation, the beginnings of a 2mm crack angled upward at 15° was added. These two simulations were used to identify whether a local stress riser was present at the hinge. This information was used to calculate the energy release rate to the hinge, which corresponds to the energy needed to initiate and propagate a crack on the hinge. RESULTS: In the first simulation (no crack initiation), a rectangular saw blade geometry resulted in the lowest local stress concentration. In the second simulation (with crack initiation), the U-shaped geometry resulted in the lowest local stress concentration. The U-shaped geometry had the lowest energy release rate, meaning that it was the least likely to initiate and propagate a crack on the lateral cortical hinge. DISCUSSION/CONCLUSION: Keeping the inherent limitations related to computer modelling in mind, our findings show that a U-shaped cutting edge is least likely to initiate or propagate a crack since it has the lowest energy release rate. This confirms our hypothesis. LEVEL OF EVIDENCE: V, expert opinion

Cystic Fibrosis airway epithelium remodelling: involvement of inflammation

International audienceChronic inflammation is a hallmark of cystic fibrosis (CF) lung disease and airway epithelium damage and remodelling are important components of lung pathology progression in CF. Whether this remodelling is secondary to deleterious infectious and inflammatory mediators, or to alterations of CF human airway epithelial (HAE) cells, such as their hyper inflammatory phenotype or their basic cystic fibrosis transmembrane conductance regulator (CFTR) default, remains debated. In this study, we evaluated the involvement of alterations of CF HAE cells in airway epithelium remodelling. HAE cells from non‐CF and CF patients were cultured in an air–liquid interface, with and without inflammatory stimulation, along the regeneration process, and the remodelling of the reconstituted epithelium was analysed. We confirmed that CF HAE cells showed a hyperinflammatory phenotype which was lost with time. In comparison to non‐CF epithelium, CF epithelium regeneration in the absence of exogenous inflammation was higher and exhibited basal cell hyperplasia. This remodelling was mimicked by inflammatory stimulation of non‐CF cells and was absent when CF HAE cells were no longer hyperinflamed. Moreover, the number of goblet cells was similar in non‐CF and CF cultures and increased equally under inflammatory stimulation. Finally, whatever the inflammatory environment, CF cultures showed a delay in ciliated cell differentiation. In conclusion, alterations of CF HAE cells partly regulate airway epithelium remodelling following injury and regeneration. This remodelling, together with goblet cell hyperplasia induced by exogenous inflammation and alteration of ciliated cell differentiation, may worsen mucociliary clearance impairment, leading to injur