Blocking tumor-educated MSC paracrine activity halts osteosarcoma progression

Purpose: Human osteosarcoma is a genetically heterogeneous bone malignancy with poor prognosis despite the employment of aggressive chemotherapy regimens. Because druggable driver mutations have not been established, dissecting the interactions between osteosarcoma cells and supporting stroma may provide insights into novel therapeutic targets.Experimental Design: By using a bioluminescent orthotopic xenograft mouse model of osteosarcoma, we evaluated the effect of tumor extracellular vesicle (EV)-educated mesenchymal stem cells (TEMSC) on osteosarcoma progression. Characterization and functional studies were designed to assess the mechanisms underlying MSC education. Independent series of tissue specimens were analyzed to corroborate the preclinical findings, and the composition of patient serum EVs was analyzed after isolation with size-exclusion chromatography.Results: We show that EVs secreted by highly malignant osteosarcoma cells selectively incorporate a membrane-associated form of TGFβ, which induces proinflammatory IL6 production by MSCs. TEMSCs promote tumor growth, accompanied with intratumor STAT3 activation and lung metastasis formation, which was not observed with control MSCs. Importantly, intravenous administration of the anti-IL6 receptor antibody tocilizumab abrogated the tumor-promoting effects of TEMSCs. RNA-seq analysis of human osteosarcoma tissues revealed a distinct TGFβ-induced prometastatic gene signature. Tissue microarray immunostaining indicated active STAT3 signaling in human osteosarcoma, consistent with the observations in TEMSC-treated mice. Finally, we isolated pure populations of EVs from serum and demonstrated that circulating levels of EV-associated TGFβ are increased in osteosarcoma patients.Conclusions: Collectively, our findings suggest that TEMSCs promote osteosarcoma progression and provide the basis for testing IL6- and TGFβ-blocking agents as new therapeutic options for osteosarcoma patients

La calidad del aceite de oliva virgen: Posibles nuevos criterios para su evaluación

The present study consists in the evaluation of twenty five parameters for determining the influence of continuous system of pastes centrifugation, discontinuous press system and partial extraction system on obtaining of virgin olive oil, and their possible utilization as new quality parameters. Also, those indexes more related to quality than to spoilt degree (acid value, peroxide value and K270) were determined. The tested oils have been obtained in three oil-mills, from three different olive varieties, in two ripening states.El presente estudio consiste en la evaluación de veinticinco variables, para determinar la influencia que los sistemas de obtención del aceite de oliva virgen (sistema continuo de centrifugación de pastas, sistema discontinuo de prensas y sistema de extracción parcial) pueden tener sobre las mismas, así como su posible utilización como nuevos parámetros de calidad para estos aceites. Parámetros que estén más relacionados con los atributos de calidad que con el grado de deterioro (índice de acidez, índice de peróxidos y K270) de estos aceites. Los aceites ensayados se han obtenido en tres almazaras industriales a partir de tres variedades diferentes de aceitunas y en dos grados de madurez

La calidad del aceite de oliva virgen: Posibles nuevos criterios para su evaluación

International audience(Cass., ass. plén., 7 déc. 2015, n° 14-18.435, D. 2015. 2556 ; RTD com. 2016. 186, obs. B. Bouloc ; JCP 2016. 57, note J.-J. Ansault et C. Gijsbers ; Gaz. Pal. 16 févr. 2016, p. 30, 257q3, obs. M.-P. Dumont-Lefrand ; Gaz. Pal. 12 janv. 2016, p. 22, 254q4, note S. Piedelièvre ; Banque et droit, n° 165, janv.-févr. 2016, p. 84, obs. N. Rontchevsky ; adde : P. Pailler, L'Assemblée plénière confirme l'absence d'option en faveur du gage de droit commun pour l'établissement de crédit qui souscrit un gage de stocks, RLDC févr. 2016, n° 6115, p. 28