Sensibilisation de cellules tumorales au cyclophosphamide par transfert de gène (de l'in vitro à l'in vivo)

Les thérapies anticancéreuses ont connu ces dernières années un développement important ayant pour conséquence une amélioration dans la qualité de vie des patients. Cependant la survenue de résistances et la part significative de cancer sans traitement efficace nous oblige à envisager le développement de nouvelles stratégies anticancéreuses. Nous avons développé une nouvelle technique basée sur le principe du gène suicide en utilisant le gène du cytochrome P450 2B6 associé au cyclophosphamide (CPA). Cette technique qui consiste au transfert d un gène métabolisant une prodrogue anticancéreuse dans la tumeur permet une sensibilisation des tumeurs à cette prodrogue. Le premier objectif de ce travail a consisté à améliorer le métabolisme de la prodrogue en construisant un gène muté du CYP2B6 en fusion avec la réductase, partenaire indispensable du CYP. Dans un deuxième temps nous avons transféré le gène CYP2B6TM-RED dans des cellules tumorales qui sont devenues sensibles au CPA entrainant une éradication des tumeurs. Ces résultats ont été confirmés in vivo sur des modèles de souris immunocompétentes. Nous avons, en plus de l effet cytotoxique, mis en évidence un important effet bystander et le développement d une immunité antitumorale spécifique. Ceci nous laisse penser que cette méthode peut permettre de protéger contre les récidives et les métastases. Les bons résultats obtenus dans le développement de cette nouvelle stratégie anticancéreuse, nous laissent espérer d un futur passage en clinique. Pour cela de nouveaux modèles animaux devront être mis au point pour optimiser le transfert du transgène dans les tumeurs.Anticancer therapies had, in recent years, an important development that results in an improvement in the quality of life of patients. However, the occurrence of resistance and the significant proportion of untreated cancer force us to consider the development of new anticancer strategies. We have developed a new technique based on the principle of suicide gene using the gene of cytochrome P450 2B6 associated with cyclophosphamide (CPA). This technique involves the transfer of a gene metabolizing an anticancer prodrug within the tumor allowing tumors sensitization to this prodrug. The first objective of this work was to improve the metabolism of the prodrug in building a mutated CYP2B6 fused with the reductase gene essential partner of CYP. In a second step we transferred the CYP2B6TM-RED gene in tumor cells that have been significantly sensitized. These results were confirmed on in vivo models of immunocompetent mice. In addition to the cytotoxic effect, mice were able to develop a specific anti-tumor immunity. This suggests to us that this method can protect against recurrence and metastasis. The good results obtained in the development of this new anticancer strategy, let us hope for a future transition into clinic. For this, new animal models will be developed to definitively validate the method.PARIS5-Bibliotheque electronique (751069902) / SudocPARIS-BIUM-Bib. électronique (751069903) / SudocSudocFranceF

Books in Arabic Script

The chapter approaches the book in Arabic script as the indispensable means for the transmission of knowledge across Eurasia and Africa, within cultures and across cultural boundaries, since the seventh century ad. The state of research can be divided into manuscript and print studies, but there is not yet a history of the book in Arabic script that captures its plurilinear development for over fourteen hundred years. The chapter explores the conceptual and practical challenges that impede the integration of the book in Arabic script into book history at large and includes an extensive reference list that reflects its diversity. The final published version was slightly updated, and includes seven illustrations of six Qurans from the holdings of Columbia University Libraries, four manuscripts and two printed versions. Moreover, the illustrations are images of historical artifacts which are in the public domain - despite Wiley's copyright claim

Sensibilisation de cellules tumorales au cyclophosphamide par transfert de gène : de l'in vitro à l'in vivo

Anticancer therapies had, in recent years, an important development that results in an improvement in the quality of life of patients. However, the occurrence of resistance and the significant proportion of untreated cancer force us to consider the development of new anticancer strategies. We have developed a new technique based on the principle of suicide gene using the gene of cytochrome P450 2B6 associated with cyclophosphamide (CPA). This technique involves the transfer of a gene metabolizing an anticancer prodrug within the tumor allowing tumors sensitization to this prodrug. The first objective of this work was to improve the metabolism of the prodrug in building a mutated CYP2B6 fused with the reductase gene essential partner of CYP. In a second step we transferred the CYP2B6TM-RED gene in tumor cells that have been significantly sensitized. These results were confirmed on in vivo models of immunocompetent mice. In addition to the cytotoxic effect, mice were able to develop a specific anti-tumor immunity. This suggests to us that this method can protect against recurrence and metastasis. The good results obtained in the development of this new anticancer strategy, let us hope for a future transition into clinic. For this, new animal models will be developed to definitively validate the method.Les thérapies anticancéreuses ont connu ces dernières années un développement important ayant pour conséquence une amélioration dans la qualité de vie des patients. Cependant la survenue de résistances et la part significative de cancer sans traitement efficace nous oblige à envisager le développement de nouvelles stratégies anticancéreuses. Nous avons développé une nouvelle technique basée sur le principe du gène suicide en utilisant le gène du cytochrome P450 2B6 associé au cyclophosphamide (CPA). Cette technique qui consiste au transfert d’un gène métabolisant une prodrogue anticancéreuse dans la tumeur permet une sensibilisation des tumeurs à cette prodrogue. Le premier objectif de ce travail a consisté à améliorer le métabolisme de la prodrogue en construisant un gène muté du CYP2B6 en fusion avec la réductase, partenaire indispensable du CYP. Dans un deuxième temps nous avons transféré le gène CYP2B6TM-RED dans des cellules tumorales qui sont devenues sensibles au CPA entrainant une éradication des tumeurs. Ces résultats ont été confirmés in vivo sur des modèles de souris immunocompétentes. Nous avons, en plus de l’effet cytotoxique, mis en évidence un important effet bystander et le développement d’une immunité antitumorale spécifique. Ceci nous laisse penser que cette méthode peut permettre de protéger contre les récidives et les métastases. Les bons résultats obtenus dans le développement de cette nouvelle stratégie anticancéreuse, nous laissent espérer d’un futur passage en clinique. Pour cela de nouveaux modèles animaux devront être mis au point pour optimiser le transfert du transgène dans les tumeurs

Sensitization of tumor cells to cyclophosphamide by gene transfer : from in vitro to in vivo

Les thérapies anticancéreuses ont connu ces dernières années un développement important ayant pour conséquence une amélioration dans la qualité de vie des patients. Cependant la survenue de résistances et la part significative de cancer sans traitement efficace nous oblige à envisager le développement de nouvelles stratégies anticancéreuses. Nous avons développé une nouvelle technique basée sur le principe du gène suicide en utilisant le gène du cytochrome P450 2B6 associé au cyclophosphamide (CPA). Cette technique qui consiste au transfert d’un gène métabolisant une prodrogue anticancéreuse dans la tumeur permet une sensibilisation des tumeurs à cette prodrogue. Le premier objectif de ce travail a consisté à améliorer le métabolisme de la prodrogue en construisant un gène muté du CYP2B6 en fusion avec la réductase, partenaire indispensable du CYP. Dans un deuxième temps nous avons transféré le gène CYP2B6TM-RED dans des cellules tumorales qui sont devenues sensibles au CPA entrainant une éradication des tumeurs. Ces résultats ont été confirmés in vivo sur des modèles de souris immunocompétentes. Nous avons, en plus de l’effet cytotoxique, mis en évidence un important effet bystander et le développement d’une immunité antitumorale spécifique. Ceci nous laisse penser que cette méthode peut permettre de protéger contre les récidives et les métastases. Les bons résultats obtenus dans le développement de cette nouvelle stratégie anticancéreuse, nous laissent espérer d’un futur passage en clinique. Pour cela de nouveaux modèles animaux devront être mis au point pour optimiser le transfert du transgène dans les tumeurs.Anticancer therapies had, in recent years, an important development that results in an improvement in the quality of life of patients. However, the occurrence of resistance and the significant proportion of untreated cancer force us to consider the development of new anticancer strategies. We have developed a new technique based on the principle of suicide gene using the gene of cytochrome P450 2B6 associated with cyclophosphamide (CPA). This technique involves the transfer of a gene metabolizing an anticancer prodrug within the tumor allowing tumors sensitization to this prodrug. The first objective of this work was to improve the metabolism of the prodrug in building a mutated CYP2B6 fused with the reductase gene essential partner of CYP. In a second step we transferred the CYP2B6TM-RED gene in tumor cells that have been significantly sensitized. These results were confirmed on in vivo models of immunocompetent mice. In addition to the cytotoxic effect, mice were able to develop a specific anti-tumor immunity. This suggests to us that this method can protect against recurrence and metastasis. The good results obtained in the development of this new anticancer strategy, let us hope for a future transition into clinic. For this, new animal models will be developed to definitively validate the method

Feature Imputation using Neutrosophic Set Theory in Machine Learning Regression Context

The prediction context of machine learning aims to discern the underlying patterns that dictate the characteristics to forecast the output. This prediction lacks precision when the input data is not accurate or precise. This study focuses on feature imputation through the application of the neutrosophic set theory. The primary concept involves substituting feature data, which may have accuracy and correctness issues, with neutrosophic variables considering the degrees of truth, indeterminacy, and falsity to produce more precise and resilient predictions. The proposed method was implemented in a specific case study, and the results are analyzed

The maximum sloshing wave height evaluation in cylindrical metallic tanks by numerical means

The metallic cylindrical storage tanks are very common structures in the field of civil engineering; These facilities are especially used in the industry in which they are used to store all kinds of products-which are for the most toxic or flammable. The tanks are also used in the storing of drinking water. When earthquakes, these structures must be strictly maintained in order to avoid that they lose their precious contents causing reactions that can cause more damage than the earthquake itself. In this study, the effects of the liquid height, the geometric parameters of tanks in the variation of the maximum sloshing wave height are studied: For this purpose, the software ANSYS V11.0 is used for modelling the tanks, the results found are compared with thus given in the Euro code

The maximum sloshing wave height evaluation in cylindrical metallic tanks by numerical means

The metallic cylindrical storage tanks are very common structures in the field of civil engineering; These facilities are especially used in the industry in which they are used to store all kinds of products-which are for the most toxic or flammable. The tanks are also used in the storing of drinking water. When earthquakes, these structures must be strictly maintained in order to avoid that they lose their precious contents causing reactions that can cause more damage than the earthquake itself. In this study, the effects of the liquid height, the geometric parameters of tanks in the variation of the maximum sloshing wave height are studied: For this purpose, the software ANSYS V11.0 is used for modelling the tanks, the results found are compared with thus given in the Euro code

Impact of outdated CSI on the secrecy performance of dual-hop networks using cooperative jamming

This paper studies the problem of secure dual-hop AF network in the presence of eavesdropper. We study the secrecy performance of partial relay selection with outdated channel state information (CSI). We propose a system secrecy where two sources and destination simultaneously transmit the legitimate and the jamming signal respectively. The selected relay forwards the combined signal to the legitimate receiver and the eavesdropper. We derive a closed-form expression for lower bound on the ergodic secrecy capacity (ESC) under different assumptions of the eavesdropper channel gains. We verify that the system performance is degraded as the correlation coefficient decreases. Simulation results are considered to verify the exactness of the proposed mathematical analysis. - 2019 IEEE.1This publication was made possible by NPRP grant # 10-0102-170094 from the Qatar National Research Fund (a member of Qatar Foundation). The statements made herein are solely the responsibility of the authors.Scopu

Secure half-duplex dual-hop AF relaying networks with partial relay selection

In this paper, we focus on the half-duplex (HD) relaying with partial relay selection (PRS) scheme using destination-assisted jamming (DAJ). We consider one source (S), one destination (D), one passive eavesdropper and multiple amplify-and-forward (AF) relays. The relay node is selected based on the best instantaneous signal-to-noise ratio (SNR) of the first hop. Closed-form expressions for lower-bound of ergodic secrecy capacity (ESC) and secrecy outage probability (SOP) are derived over independent and identically distributed (i.i.d.) Rayleigh fading environment. Moreover, we present a comparison between the proposed system and the secure AF relaying system with reactive relay selection (RRS). In the RRS, the relay is chosen based on the best SNR of the second hop. Simulation results are presented to verify the exactness of our proposed mathematical analysis. - 2019 IEEE.1This publication was made possible by NPRP grant # 10-0102-170094 from the Qatar National Research Fund (a member of Qatar Foundation). The statements made herein are solely the responsibility of the authors.Scopu