Neurokinin-1 receptor as a therapeutic target in hepatoblastoma

The neurokinin-1 receptor (NK1R) has recently been described as being pivotal in the development of cancer. NK1R antagonists, such as the clinical drug aprepitant, are therefore under current investigation as future innovative anticancer agents. However, little is known about the NK1R complex as a potential target in hepatoblastoma and colon cancer cells. Thus, we aimed at investigating the impact of NK1R inhibition with aprepitant on cell growth, apoptosis, downstream mechanims and cancer stem cells in three human hepatoblastoma cell lines HepT1, HepG2 and HuH6 and the human colon cancer cell lines LiM6 and DLD1. Finally, mRNA from 47 children with hepatoblastoma were analysed regarding both full length and truncated forms of NK1R. NK1R is highly expressed in human hepatoblastoma cell lines predominantly in its truncated version. Following NK1R blockage by aprepitant, a significant growth inhibition of hepatoblastoma cells and colon cancer cells as well as induction of apoptosis was detected, which was associated with the downregulation of two critical signaling pathways, namely Wnt and PI3K/AKT/mTOR. Further, treatment of colon cancer or hepatoblastoma cells grown under cancer stem cell conditions reduced sphere formation in number and size as well as expression of the stemness markers SOX2, NANOG, and OCT4. From a clinical perspective, both forms of NK1R were generally overexpressed in hepatoblastoma cases, without any correlation with clinicopathological parameters indicating that aprepitant might be used in a wide variety of hepatoblastoma. Taken together, these findings give important insight into the molecular mechanisms of the NK1R as a critical component in tumorigenesis and can help in the development of future anticancer therapies for Wnt-activated cancers such as hepatoblastoma and colon cancer

Neurokinin-1 receptor as a therapeutic target in hepatoblastoma

The neurokinin-1 receptor (NK1R) has recently been described as being pivotal in the development of cancer. NK1R antagonists, such as the clinical drug aprepitant, are therefore under current investigation as future innovative anticancer agents. However, little is known about the NK1R complex as a potential target in hepatoblastoma and colon cancer cells. Thus, we aimed at investigating the impact of NK1R inhibition with aprepitant on cell growth, apoptosis, downstream mechanims and cancer stem cells in three human hepatoblastoma cell lines HepT1, HepG2 and HuH6 and the human colon cancer cell lines LiM6 and DLD1. Finally, mRNA from 47 children with hepatoblastoma were analysed regarding both full length and truncated forms of NK1R. NK1R is highly expressed in human hepatoblastoma cell lines predominantly in its truncated version. Following NK1R blockage by aprepitant, a significant growth inhibition of hepatoblastoma cells and colon cancer cells as well as induction of apoptosis was detected, which was associated with the downregulation of two critical signaling pathways, namely Wnt and PI3K/AKT/mTOR. Further, treatment of colon cancer or hepatoblastoma cells grown under cancer stem cell conditions reduced sphere formation in number and size as well as expression of the stemness markers SOX2, NANOG, and OCT4. From a clinical perspective, both forms of NK1R were generally overexpressed in hepatoblastoma cases, without any correlation with clinicopathological parameters indicating that aprepitant might be used in a wide variety of hepatoblastoma. Taken together, these findings give important insight into the molecular mechanisms of the NK1R as a critical component in tumorigenesis and can help in the development of future anticancer therapies for Wnt-activated cancers such as hepatoblastoma and colon cancer

Introducción

There are miraculous encounters. Under the good auspices of Cartagena de Indias, collaboration began between the Francisco José de Caldas District University (Colombia) and the Jean-Jaurès University of Toulouse (France). In the framework of a meeting organized by the Colombian Association of Universities (ASCUN) entitled "A contribution to public policy on Doctoral training in Colombia", the University of Toulouse was invited to present the organization of the doctoral diploma in March 2015 in France, following a project newly coined in Toulouse as the School of Doctors. This school that brings together 4,500 doctoral students and 7,000 researchers could be an example to enhance the dynamics of research and innovation through doctoral studentsHay encuentros milagrosos. Bajo los buenos auspicios de Cartagena de Indias empezó la colaboración entre la Universidad Distrital Francisco José de Caldas (Colombia) y la Universidad de Toulouse Jean-Jaurès (Francia). En el marco de un encuentro organizado por la Asociación Colombiana de Universidades (ASCUN) titulada “Un aporte a la política pública sobre la formación Doctoral en Colombia”, la Universidad de Toulouse fue invitada a presentar en marzo del 2015 la organización del diploma de doctorado en Francia, a raíz de un proyecto nuevamente acuñado en Toulouse como Escuela de Doctores. Esta escuela que reúne a 4.500 doctorandos y 7.000 investigadores podía ser un ejemplo para potenciar la dinámica de la investigación e innovación a través de los doctorandosExistem encontros milagrosos. Sob os bons auspícios de Cartagena das Índias, a colaboração começou entre a Universidade do Distrito Francisco José de Caldas (Colômbia) e a Universidade Jean-Jaurès de Toulouse (França). No âmbito de uma reunião organizada pela Associação Colombiana de Universidades (ASCUN) intitulada "Uma contribuição para as políticas públicas de formação de doutorado na Colômbia", a Universidade de Toulouse foi convidada a apresentar a organização do diploma de doutorado em março de 2015 na França, na sequência de um projeto recentemente cunhado em Toulouse como a Escola de Médicos. Esta escola que reúne 4.500 doutorandos e 7.000 pesquisadores pode ser um exemplo para aprimorar a dinâmica da pesquisa e inovação por meio de doutorando

Quelle articulation entre les pôles de compétitivité et les tissus productifs régionaux ?: Une mise en perspective de quatre pôles en Provence-Alpes-Côte d'Azur

L'objectif de ce travail de recherche était de mettre en lumière les conditions de mise en œuvre et les bénéfices attendus de quatre pôles de compétitivité de la région PACA (Solutions communicantes sécurisées ; Mer, sécurité et sûreté, Développement durable ; Fruits et légumes ; Parfums, arômes, senteurs, saveurs). Le questionnement e a été décliné suivant deux axes : 1/ quelle est la capacité réelle de ces dispositifs à produire, diffuser et utiliser des ressources scientifiques et techniques ? Les pôles de compétitivité ont en charge de produire de nouvelles ressources dans des tissus productifs préexistants. Comment s'articulent ces nouvelles ressources avec celles déjà existantes ? Sont-elles susceptibles de se féconder mutuellement ? Mais dans le même temps, n'y a-t-il pas des risques de polarisation de l'activité et de ce fait, des risques d'exclusion ? 2/ quelle est la capacité réelle du nouveau dispositif à susciter et installer durablement la coopération nécessaire à la création des ressources attendues

The Kembs project: environmental integration of a large existing hydropower scheme

The environment was a major issue for the Kembs relicensing process on the upper Rhin River. Since 1932, Kembs dam derives water from the Rhine River to the "Grand Canal d'Alsace" (GCA) which is equipped with four hydropower plants (max. diverted flow: 1400 m3/s, 630 MW, 3760 GWh/y). The Old Rhine River downstream of the dam is 50 km long and has been strongly affected by works (dikes) since the 19th century for flood protection and navigation, and then by the construction of the dam. Successive engineering works induced morphological simplification and stabilization of the channel pattern from a formerly braided form to a single incised channel, generating ecological alterations. As the Kembs hydroelectric scheme concerns three countries (France, Germany and Switzerland) with various regulations and views on how to manage with environment, EDF undertook an integrated environmental approach instead of a strict "impact/mitigation" balance that took 10 years to develop. Therefore, the project simultaneously acts on complementary compartments of the aquatic, riparian and terrestrial environment, to benefit from the synergies that exist between them ; a new powerplant (8,5 MW, 28 GWh/y) is built to limit the energetic losses and to ensure various functions thereby increasing the overall environmental gain

Introducción

There are miraculous encounters. Under the good auspices of Cartagena de Indias, collaboration began between the Francisco José de Caldas District University (Colombia) and the Jean-Jaurès University of Toulouse (France). In the framework of a meeting organized by the Colombian Association of Universities (ASCUN) entitled "A contribution to public policy on Doctoral training in Colombia", the University of Toulouse was invited to present the organization of the doctoral diploma in March 2015 in France, following a project newly coined in Toulouse as the School of Doctors. This school that brings together 4,500 doctoral students and 7,000 researchers could be an example to enhance the dynamics of research and innovation through doctoral studentsExistem encontros milagrosos. Sob os bons auspícios de Cartagena das Índias, a colaboração começou entre a Universidade do Distrito Francisco José de Caldas (Colômbia) e a Universidade Jean-Jaurès de Toulouse (França). No âmbito de uma reunião organizada pela Associação Colombiana de Universidades (ASCUN) intitulada "Uma contribuição para as políticas públicas de formação de doutorado na Colômbia", a Universidade de Toulouse foi convidada a apresentar a organização do diploma de doutorado em março de 2015 na França, na sequência de um projeto recentemente cunhado em Toulouse como a Escola de Médicos. Esta escola que reúne 4.500 doutorandos e 7.000 pesquisadores pode ser um exemplo para aprimorar a dinâmica da pesquisa e inovação por meio de doutorandosHay encuentros milagrosos. Bajo los buenos auspicios de Cartagena de Indias empezó la colaboración entre la Universidad Distrital Francisco José de Caldas (Colombia) y la Universidad de Toulouse Jean-Jaurès (Francia). En el marco de un encuentro organizado por la Asociación Colombiana de Universidades (ASCUN) titulada “Un aporte a la política pública sobre la formación Doctoral en Colombia”, la Universidad de Toulouse fue invitada a presentar en marzo del 2015 la organización del diploma de doctorado en Francia, a raíz de un proyecto nuevamente acuñado en Toulouse como Escuela de Doctores. Esta escuela que reúne a 4.500 doctorandos y 7.000 investigadores podía ser un ejemplo para potenciar la dinámica de la investigación e innovación a través de los doctorando

Deux vases turons mutilés et inscrits du Haut-Empire : des objets entre pharmacopée et pratiques magiques?

International audienceThe discovery of two mutilated vases, a 1st century flask and a 2nd-3rd century carinated beaker in Amboise and Tours (Indre-et-Loire), bearing partially similar graffiti, is the source of the present study. Thus, the first vase contained a therapeutic preparation intended, according to Pliny the Elder, to treat a skin infection, while the second, partially charred, contained poached red wine. Comparisons made with the graffiti - a similar sign to the letter A, an eight-pointed star and the beginning of a Greek alphabet engraved on one of the vases - lead to the identification of charaktêres, similar to those found on some beneficial magic amulets, intended to reinforce the effectiveness of medical products. These vases would thus testify to the porosity of the boundaries between "pharmacopoeia" type knowledge and magical rites. They also open up avenues of reflection concerning the mutilations observed, probably in connection with disease transfer rites.La découverte de deux vases mutilés, un flacon du Ier siècle et un gobelet caréné du II-IIIe siècle apr. J.-C. à Amboise et à Tours (Indre-et-Loire) porteurs de graffiti partiellement similaires sont à la source de la présente étude. Ainsi, le premier vase contenait une préparation à caractère thérapeutique destinée, selon Pline l’Ancien, au traitement d’une infection cutanée, tandis que le second, partiellement calciné, contenait du vin rouge poissé. Les comparaisons effectuées pour les graffiti – un signe apparenté à la lettre A, une étoile à 8 branches et le début d’un abécédaire grec gravé sur l’un des vases, conduisent à identifier des charaktêres, analogues à ceux figurant sur quelques amulettes magiques bénéfiques, destinées à renforcer l’efficacité des préparations médicinales. Ces vases témoigneraient ainsi de la porosité des frontières entre un savoir de type « pharmacopée » et des rites magiques. Ils permettent en outre d’ouvrir des pistes de réflexions concernant les mutilations observées, ici probablement en lien avec des rites de transfert de maladies

Deux vases turons mutilés et inscrits du Haut-Empire : des objets entre pharmacopée et pratiques magiques?

International audienceThe discovery of two mutilated vases, a 1st century flask and a 2nd-3rd century carinated beaker in Amboise and Tours (Indre-et-Loire), bearing partially similar graffiti, is the source of the present study. Thus, the first vase contained a therapeutic preparation intended, according to Pliny the Elder, to treat a skin infection, while the second, partially charred, contained poached red wine. Comparisons made with the graffiti - a similar sign to the letter A, an eight-pointed star and the beginning of a Greek alphabet engraved on one of the vases - lead to the identification of charaktêres, similar to those found on some beneficial magic amulets, intended to reinforce the effectiveness of medical products. These vases would thus testify to the porosity of the boundaries between "pharmacopoeia" type knowledge and magical rites. They also open up avenues of reflection concerning the mutilations observed, probably in connection with disease transfer rites.La découverte de deux vases mutilés, un flacon du Ier siècle et un gobelet caréné du II-IIIe siècle apr. J.-C. à Amboise et à Tours (Indre-et-Loire) porteurs de graffiti partiellement similaires sont à la source de la présente étude. Ainsi, le premier vase contenait une préparation à caractère thérapeutique destinée, selon Pline l’Ancien, au traitement d’une infection cutanée, tandis que le second, partiellement calciné, contenait du vin rouge poissé. Les comparaisons effectuées pour les graffiti – un signe apparenté à la lettre A, une étoile à 8 branches et le début d’un abécédaire grec gravé sur l’un des vases, conduisent à identifier des charaktêres, analogues à ceux figurant sur quelques amulettes magiques bénéfiques, destinées à renforcer l’efficacité des préparations médicinales. Ces vases témoigneraient ainsi de la porosité des frontières entre un savoir de type « pharmacopée » et des rites magiques. Ils permettent en outre d’ouvrir des pistes de réflexions concernant les mutilations observées, ici probablement en lien avec des rites de transfert de maladies