Les concepts de matrice offensive et défensive envisagés sous l’angle de la didactique des sports collectifs

Cet article se veut un hommage au travail de René Deleplace en rugby, Robert Mérand en basket-ball et quelques autres qui ont été à la source d’un pan important de la réflexion sur la didactique et la pédagogie des sports collectifs en France. Il s’agit de questionner à nouveau certains concepts utiles pour mieux fonder la didactique des sports collectifs à l’école. En effet, le désarroi produit par les ambitions démesurées du programme d’EPS au lycée n’a pas permis d’avancées significatives sur l’enseignement de ceux-ci. Comme énoncé par Godbout (2001), nous pensons que dans les années à venir, un de nos défis en tant que chercheurs en didactique et en technologie des sports collectifs sera de développer l’impact et la diffusion des recherches fondatrices des pratiques enseignantes en répondant aux trois questions majeures suivantes : Qu’enseignent réellement les enseignants ? Qu’apprennent les élèves en pratiquant des activités physiques et sportives ? Quelles étapes jalonnent le développement du pratiquant ?Les connaissances qui permettent, à l’école, de passer du débutant au débrouillé, du débutant à l’expert au moyen des pratiques sociales de références sont à explorer. Cet article tente d’apporter un état des lieux des connaissances face à ce véritable défi dont l’enjeu est la présence même, au sein du système scolaire, des sports collectifs, et par extension de l’EPS (cf. Rapport Thélot 2004)

The detrimental invasiveness of glioma cells controlled by gadolinium chelate-coated gold nanoparticles

International audienceGlioblastoma are characterized by an invasive phenotype, which is thought to be responsible for recurrences and the short overall survival of patients. In last decade, the promising potential of ultrasmall gadolinium chelate-coated gold nanoparticles (namely Au@DTDTPA(Gd)) was evidenced for image-guided radiotherapy in brain tumors. Considering the threat posed by invasiveness properties of glioma cells, we were interested to further investigate the biological effects of Au@DTDTPA(Gd) by examining their impact on GBM cell migration and invasion. In our work, exposure of U251 glioma cells to Au@DTDTPA(Gd) led into high accumulation of gold nanoparticles, that were mainly diffusely distributed in the cytoplasm of the tumor cells. Experiments pointed out a significant decrease in glioma cells invasiveness when exposed to nanoparticles. As the proteolysis activities were not directly affected by the intracytoplasmic accumulation of Au@DTDTPA(Gd), the anti-invasive effect cannot be attributed to a matrix remodeling impairment. Rather, Au@DTDTPA(Gd) nanoparticles affected the intrinsic biomechanical properties of U251 glioma cells, such as cell stiffness, adhesion and generated traction forces, and significantly reduced the formation of protrusions, thus exerting an inhibitory effect on their migration capacities. These results highlight the interest of Au@DTDTPA(Gd) nanoparticles for the therapeutic management of astrocytic tumors, not only as radio-enhancing agent but also by reducing invasive potential of glioma cells

A novel Fc-engineered cathepsin D-targeting antibody enhances ADCC, triggers tumor-infiltrating NK cell recruitment, and improves treatment with paclitaxel and enzalutamide in triple-negative breast cancer

International audienceIntroduction: Triple-negative breast cancer (TNBC) prognosis is poor. Immunotherapies to enhance the antibody-induced natural killer (NK) cell antitumor activity are emerging for TNBC that is frequently immunogenic. The aspartic protease cathepsin D (cath-D), a tumor cell-associated extracellular protein with protumor activity and a poor prognosis marker in TNBC, is a prime target for antibody-based therapy to induce NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC). This study investigated whether Fc-engineered anti-cath-D antibodies trigger ADCC, their impact on antitumor efficacy and tumor-infiltrating NK cells, and their relevance for combinatory therapy in TNBC.Methods: Cath-D expression and localization in TNBC samples were evaluated by western blotting, immunofluorescence, and immunohistochemistry. The binding of human anti-cath-D F1M1 and Fc-engineered antibody variants, which enhance (F1M1-Fc + ) or prevent (F1M1-Fc − ) affinity for CD16a, to secreted human and murine cath-D was analyzed by ELISA, and to CD16a by surface plasmon resonance and flow cytometry. NK cell activation was investigated by flow cytometry, and ADCC by lactate dehydrogenase release. The antitumor efficacy of F1M1 Fc-variants was investigated using TNBC cell xenografts in nude mice. NK cell recruitment, activation, and cytotoxic activity were analyzed in MDA-MB-231 cell xenografts by immunophenotyping and RT-qPCR. NK cells were depleted using an anti-asialo GM1 antibody. F1M1-Fc + antitumor effect was assessed in TNBC patient-derived xenografts (PDXs) and TNBC SUM159 cell xenografts, and in combination with paclitaxel or enzalutamide.Results Cath-D expression on the TNBC cell surface could be exploited to induce ADCC. F1M1 Fc-variants recognized human and mouse cath-D. F1M1-Fc + activated NK cells in vitro and induced ADCC against TNBC cells and cancer-associated fibroblasts more efficiently than F1M1. F1M1-Fc − was ineffective. In the MDA-MB-231 cell xenograft model, F1M1-Fc + displayed higher antitumor activity than F1M1, whereas F1M1-Fc − was less effective, reflecting the importance of Fc-dependent mechanisms in vivo. F1M1-Fc + triggered tumor-infiltrating NK cell recruitment, activation and cytotoxic activity in MDA-MB-231 cell xenografts. NK cell depletion impaired F1M1-Fc + antitumor activity, demonstrating their key role. F1M1-Fc + inhibited growth of SUM159 cell xenografts and two TNBC PDXs. In combination therapy, F1M1-Fc + improved paclitaxel and enzalutamide therapeutic efficacy without toxicity.Conclusions F1M1-Fc + is a promising immunotherapy for TNBC that could be combined with conventional regimens, including chemotherapy or antiandrogens