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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Avaliação de maçã Royal Gala revestida com filme de quitosana durante o período de pós-colheita

Jorge, Paula Canonico Silva [UNESP] 24 November 2010 (has links) (PDF)
Made available in DSpace on 2014-06-11T19:23:32Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-11-24Bitstream added on 2014-06-13T20:50:29Z : No. of bitstreams: 1 jorge_pcs_me_arafcf.pdf: 737046 bytes, checksum: dec84c3ab28e6bf448b4986f93072480 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Os filmes e revestimentos biodegradáveis são usados para revestir os alimentos, agindo como barreira à umidade e a gases, reduzindo a respiração e as perdas de água por transpiração e desidratação, além do escurecimento enzimático, e mantendo as características do alimento, com aumento da vida de prateleira. Este trabalho teve como objetivos reunir informações sobre o uso da quitosana como revestimento de frutas e vegetais, visando dar suporte ao trabalho experimental; avaliar maçãs revestidas com quitosana comercial, durante o armazenamento à temperatura ambiente, simulando as condições de comercialização das frutas para o mercado interno; avaliar maçãs revestidas com quitosana comercial durante 6 meses de armazenamento sob atmosfera controlada e baixa temperatura, condições de estocagem das frutas para o mercado externo, seguido de armazenamento por 30 dias em atmosfera ambiente e baixa temperatura, visando simular o transporte das frutas para o mercado consumidor no exterior, e posteriormente estocadas à temperatura ambiente, simulando as condições de comercialização; e avaliar maçãs revestidas com quitosana modificada, quando submetidas à temperatura ambiente, visando prolongar a vida de prateleira durante a comercialização, após 6 meses de armazenamento sob atmosfera controlada e baixa temperatura, seguidos de armazenamento por 30 dias em atmosfera ambiente e baixa temperatura. Maçãs ‘Royal Gala’ foram produzidas na safra de 2009, e após a colheita foram separadas em 3 lotes, sendo as frutas do 1o lote revestidas com quitosana comercial; as do 2o lote imersas em solução de ácido acético, que foram usadas como branco e as maçãs do 3o lote não receberam tratamento e foram usadas como controle. Após 6 meses de armazenamento sob atmosfera controlada e baixa temperatura, seguido de mais 30 dias de armazenamento em atmosfera ambiente... / The films and biodegradable coatings are used to coat the food, acting as a barrier to moisture and gases, reducing the respiration and water loss by transpiration and dehydration in addition to the enzymatic browning, maintaining the characteristics of food, with increased of shelf life. This study aimed to gather information about the use of chitosan as a coating for fruits and vegetables, aiming to support the experimental work; evaluate apples coated with commercial chitosan coating during storage at ambient temperature, simulating the real conditions of sale of the fruit for the domestic market; evaluate apples coated with commercial chitosan during 6 months of storage under controlled atmosphere and low temperature, storage conditions of fruit for the export market, followed by 30 days storage under at ambient and low temperature, in order to simulate the transport of fruit to the consumer market abroad, and subsequently stored at ambient temperature, simulating the conditions of marketing; and evaluate apples coated with modified chitosan, at ambient temperature, in order to prolong the shelf life during marketing after six months storaged under controlled atmosphere and low temperature, followed by another 30 days storage under at ambient atmosphere and low temperature. ‘Royal Gala’ apples were produced in 2009 crop and after the harvest they were separated into 3 lots, the first batch of fruit coated with commercial chitosan, those from second lot were immersed in an acetic acid solution and used as blank and the third lot of apples used as controls received no treatment. After 6 storage months under controlled atmosphere and low temperature, followed by another 30 days storage under at ambient atmosphere and low temperature apples without any treatment were separated in 2 lots, being the first batch of fruit coated with modified chitosan, and the second batch used as controls... (Complete abstract click electronic access below)
2

Influence of crop based water and nutrient strategies on physiological aspects of apple trees ‘Brookfield Gala’

Lebese, Thabiso C. 12 1900 (has links)
Thesis (PhD(Agric) (Horticulture))--Stellenbosch University, 2008. / It is a common practise in the Western Cape to use micro sprinklers as the standard irrigation system for apple trees. Over the past forty years much effort has been put into the optimisation of the tree canopy. Less attention has been given to root proliferation, and the question as to whether root stimulation and proliferation, through intensive water and nutrient management, can contribute towards improved tree efficiency and more efficient water use. This is addressed in this study. ‘Brookfield Gala’ apple trees were studied in the Genadendal area near Greyton, in the Western Cape Province, South Africa. The trees were planted in Dundee soil (well aerated sandy loam soil) during winter 2003. Both horticultural aspects (tree growth, shoot growth, fruit yield and quality, trunk circumference and root growth) and gas exchange were studied from 2004/5 until 2007/8 under three different water application strategies, namely micro sprinkler irrigation, daily drip and pulsing drip irrigation and using two different rootstocks: M793 and M7. Irrigation under micro sprinkler irrigation was applied once to three times weekly, daily drip irrigation once daily/twice daily, and pulsing drip irrigation one to six times daily. Water use for bearing apple trees was calculated using long-term evaporation data (for Villiersdorp and Caledon) and existing crop factors for apples. Annual nutrient requirements were adapted from literature and divided percentage-wise into the requirements for five different phenological stages. Soil sensors were used to keep plant available soil water between 100% and 50%. A computer software program was used to incorporate all the above mentioned information and calculate the exact amounts of water and nutrients, and the application times. In general, drip irrigation systems used ±26% less water than micro sprinkler irrigation system. Significantly higher fruit yields were obtained with trees under daily or pulsing drip irrigation than those under micro irrigation during 2005/6 and 2007/8. During 2006/7 the crop load was low due to unfavourable weather conditions during flowering, resulting in poor fruit set and no differences in yield. There was a significantly higher number of thin plus medium roots (3mm and less in diameter) in the 0─400mm rooting zone and total root mass at 0─800mm rooting zone under drip irrigation systems than under micro sprinkler irrigation. Brookfield Gala’ apple trees grown under daily drip irrigation and pulsing drip irrigation performed better compared to those grown under micro sprinkler irrigation with respect to CO2 assimilation rate (A), stomatal conductance (gs), water use efficiency (WUE) and leaf water potential. None of the three irrigation systems affected the biochemical efficiency of the leaf significantly, except on a few occasions during the pre-harvest period. This implied that the changes in leaf biochemical efficiency were as a result of both stomatal and non-stomatal effects (temperature and vapour pressure deficit). The removal of fruit at harvest had a great influence on leaf photosynthetic capacity under micro irrigation but less so under drip irrigation systems. Higher chlorophyll a and chlorophyll b concentrations were observed under drip irrigation systems than under micro sprinkler irrigation, implying efficient biochemical efficiency under these systems compared to micro sprinkler irrigation during the post-harvest period. Use of daily drip irrigation and pulsing drip irrigation delayed the process of leaf ageing. This study demonstrated the benefits of more intensive water and nutrient application for apple trees. Improved root proliferation, increased fruit yield and photosynthetic efficiency have been found under drip irrigation system than under micro sprinkler irrigation.
3

Dance Gala 2016: navigating stage management in dance

Brauner, Nathan 01 May 2017 (has links)
No description available.
4

En tävling för inbördes beundran? : en explorativ studie av fenomenet Galor

Ellström, Maria, Stenman, Emelia January 2008 (has links)
<p>Vi befinner oss i ett nytt medielandskap, där marknadsföringsutvecklingen kontinuerligt bygger på nya teorier och strategier för att uppnå fördelaktiga och hållbara konkurrensmedel.Uppsatsens syfte är att göra en explorativ studie om fenomenet galor.Detta sker utifrån teorier om kommunikation, varumärkesuppbyggnad samt köpbeslutsprocessen.</p><p>Frågeställningarna syftar till att först och främst beskriva varför en gala arrangeras?</p><p>Följfrågor är: Vilka mål har de olika aktörerna med galan? Vilka medel används för att uppnå målen? Men även hur uppdragsgivare, pristagare och arrangörer förhåller sig gentemot varandra? Det vill säga vilka attityder upplevs, och vad är egentligen prisets effekt?</p><p>För att kunna få en så bra inblick som möjligt utförde vi en kvalitativundersökning, som grundades på sex stycken intervjuer, med aktuella aktörer inom Guldäggsgalan och Spinngalan. Övrigt material som används är litteratur inom marknadsföring, kommunikation samt forskning för småskaliga forskningsobjekt. Vi har även kortfattat beskrivit våra studieobjekt Spinngalan och Guldäggsgalan. Det vi kommer fram till är att ett vunnet pris inom en gala kan användas som ett komplement till den befintliga marknadsföringen. Priset genererar även positiva synergieffekter för alla medverkande parter, exempelvis som ökad status, image och ökad varumärkeskännedom. Vi drar även slutsatser att rekrytering och försäljning samt val av arbetspartner i viss mån kan kopplas till prisets effekt.</p>
5

En tävling för inbördes beundran? : en explorativ studie av fenomenet Galor

Ellström, Maria, Stenman, Emelia January 2008 (has links)
Vi befinner oss i ett nytt medielandskap, där marknadsföringsutvecklingen kontinuerligt bygger på nya teorier och strategier för att uppnå fördelaktiga och hållbara konkurrensmedel.Uppsatsens syfte är att göra en explorativ studie om fenomenet galor.Detta sker utifrån teorier om kommunikation, varumärkesuppbyggnad samt köpbeslutsprocessen. Frågeställningarna syftar till att först och främst beskriva varför en gala arrangeras? Följfrågor är: Vilka mål har de olika aktörerna med galan? Vilka medel används för att uppnå målen? Men även hur uppdragsgivare, pristagare och arrangörer förhåller sig gentemot varandra? Det vill säga vilka attityder upplevs, och vad är egentligen prisets effekt? För att kunna få en så bra inblick som möjligt utförde vi en kvalitativundersökning, som grundades på sex stycken intervjuer, med aktuella aktörer inom Guldäggsgalan och Spinngalan. Övrigt material som används är litteratur inom marknadsföring, kommunikation samt forskning för småskaliga forskningsobjekt. Vi har även kortfattat beskrivit våra studieobjekt Spinngalan och Guldäggsgalan. Det vi kommer fram till är att ett vunnet pris inom en gala kan användas som ett komplement till den befintliga marknadsföringen. Priset genererar även positiva synergieffekter för alla medverkande parter, exempelvis som ökad status, image och ökad varumärkeskännedom. Vi drar även slutsatser att rekrytering och försäljning samt val av arbetspartner i viss mån kan kopplas till prisets effekt.
6

Personajes femeninos en el teatro de Antonio Gala: Anillos para una dama, Los buenos días perdidos, y ¿Por qué corres, Ulises?

Rodríguez Olay, Lucía 07 April 2010 (has links)
La tesis que se presenta tratará de dar respuesta a las siguientes formulaciones: ¿estas obras de Antonio Gala logran superar las estructuras patriarcales? ¿Son sus personajes femeninos ejemplos de tal superación?Si hablamos de estructuras patriarcales es porque nuestra visión crítica se basará en una visión de género, en una interpretación textual en la que las mujeres, su identificación y simbolización son el punto de partida. Desde que en la Ilustración comenzaran a formularse los primeros postulados teóricos acerca de la situación de las mujeres hasta nuestros días, se han sucedido diversos movimientos feministas con diferentes concepciones sobre lo que debía ser el cambio o cómo llegar a la tan deseada y nombrada igualdad. En mi tesis me situaré cercana, fundamentalmente, al feminismo de tradición ilustrada o feminismo de la igualdad que aboga por la superación de los géneros. La elección de estas tres obras ha sido determinada por el análisis de los personajes de los tres dramas; cada una de ellas representa los cuatro arquetipos básicos de la mujer a lo largo de la literatura y, en consecuencia, en la sociedad. Dichos arquetipos serían: reinas, diosas, madres y prostitutas. Es decir, las figuras de mujeres históricas, -Jimena-, mujeres protagonistas de los grandes mitos de la cultura grecolatina,-Penélope y Nausica-, mujeres bajo el prisma de la maternidad como revisión de los modelos culturales de la época-Hortensia y Consuelito-y las mujeres que ejercen de prostitutas tanto en la concepción literaria como en la social, Hortensia-.La perspectiva de género no debería ser específica de las mujeres, debería suponer una nueva construcción crítica para toda la sociedad, una nueva mirada sobre la realidad; una mirada que sea capaz de articular esas diferencias que marcan, aun hoy, la opresión, o si queremos, la desigualdad a la que se ven sometidas las mujeres y que trae como consecuencia graves problemas que nos afectan hoy día. Analizar estas tres obras desde esta perspectiva supone una mirada nueva; quisiera que fuese una mirada enriquecedora, que arrojase una luz diferente a los que se acercan a ellas. En definitiva, una mirada aperturista que dé nombre a los problemas que nos plantearán los personajes que Gala crea en estas obras y que son-categorizados de diferente forma- símbolos, no solo de las mujeres de la España de los 70, sino también de concepciones universales de las mujeres.
7

Avaliação de maçã "Royal Gala" revestida com filme de quitosana durante o período de pós-colheita /

Jorge, Paula Canonico Silva. January 2010 (has links)
Orientador: Magali C. Monteiro da Silva / Banca: Natália Soares Janzantti / Banca: Renata de Marchi / Resumo: Os filmes e revestimentos biodegradáveis são usados para revestir os alimentos, agindo como barreira à umidade e a gases, reduzindo a respiração e as perdas de água por transpiração e desidratação, além do escurecimento enzimático, e mantendo as características do alimento, com aumento da vida de prateleira. Este trabalho teve como objetivos reunir informações sobre o uso da quitosana como revestimento de frutas e vegetais, visando dar suporte ao trabalho experimental; avaliar maçãs revestidas com quitosana comercial, durante o armazenamento à temperatura ambiente, simulando as condições de comercialização das frutas para o mercado interno; avaliar maçãs revestidas com quitosana comercial durante 6 meses de armazenamento sob atmosfera controlada e baixa temperatura, condições de estocagem das frutas para o mercado externo, seguido de armazenamento por 30 dias em atmosfera ambiente e baixa temperatura, visando simular o transporte das frutas para o mercado consumidor no exterior, e posteriormente estocadas à temperatura ambiente, simulando as condições de comercialização; e avaliar maçãs revestidas com quitosana modificada, quando submetidas à temperatura ambiente, visando prolongar a vida de prateleira durante a comercialização, após 6 meses de armazenamento sob atmosfera controlada e baixa temperatura, seguidos de armazenamento por 30 dias em atmosfera ambiente e baixa temperatura. Maçãs 'Royal Gala' foram produzidas na safra de 2009, e após a colheita foram separadas em 3 lotes, sendo as frutas do 1o lote revestidas com quitosana comercial; as do 2o lote imersas em solução de ácido acético, que foram usadas como branco e as maçãs do 3o lote não receberam tratamento e foram usadas como controle. Após 6 meses de armazenamento sob atmosfera controlada e baixa temperatura, seguido de mais 30 dias de armazenamento em atmosfera ambiente... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The films and biodegradable coatings are used to coat the food, acting as a barrier to moisture and gases, reducing the respiration and water loss by transpiration and dehydration in addition to the enzymatic browning, maintaining the characteristics of food, with increased of shelf life. This study aimed to gather information about the use of chitosan as a coating for fruits and vegetables, aiming to support the experimental work; evaluate apples coated with commercial chitosan coating during storage at ambient temperature, simulating the real conditions of sale of the fruit for the domestic market; evaluate apples coated with commercial chitosan during 6 months of storage under controlled atmosphere and low temperature, storage conditions of fruit for the export market, followed by 30 days storage under at ambient and low temperature, in order to simulate the transport of fruit to the consumer market abroad, and subsequently stored at ambient temperature, simulating the conditions of marketing; and evaluate apples coated with modified chitosan, at ambient temperature, in order to prolong the shelf life during marketing after six months storaged under controlled atmosphere and low temperature, followed by another 30 days storage under at ambient atmosphere and low temperature. 'Royal Gala' apples were produced in 2009 crop and after the harvest they were separated into 3 lots, the first batch of fruit coated with commercial chitosan, those from second lot were immersed in an acetic acid solution and used as blank and the third lot of apples used as controls received no treatment. After 6 storage months under controlled atmosphere and low temperature, followed by another 30 days storage under at ambient atmosphere and low temperature apples without any treatment were separated in 2 lots, being the first batch of fruit coated with modified chitosan, and the second batch used as controls... (Complete abstract click electronic access below) / Mestre
8

Non-Destructive Evaluation of Apple Maturity Using an Electronic Nose System

Pathange, Lakshmi Prasad 07 May 2003 (has links)
The apple growers and packaging houses are interested in methods that can evaluate the quality of apples non-destructively. Harvested fruits are a mixture of immature, mature, and over mature fruits, thereby posing a great problem in deciding their end use and storage time. It is expected that the technique developed from the present project could be effectively used to classify the harvested fruit into immature, mature and over mature apples, rapidly and non-destructively. It would also help the growers to predict the optimum dates to harvest the fruits. York and Gala were the varieties of apples that were used in this study and were obtained from Virginia Tech College of Agriculture and Life Sciences Kentland Farm. Apples were harvested at different times resulting in different maturity groups (immature, mature and ripe). Gala apples were harvested on three dates with an interval of 10 days, while York apples were harvested on four dates with an interval of 14 days. They were stored at 0oC until sampled. For each harvest date, the experiments were conducted in two sets (10 each) on two consecutive days. First the ethylene levels were measured, followed by gas chromatograph and electronic nose. Then the maturity indices were measured. Three maturity indices, starch index, firmness and soluble solids were used as the three variables for the statistical analysis to identify and categorize the fruits into three maturity categories referred as immature, mature and over mature fruits. Apples were also categorized into three maturity groups based on the emanation levels of the aroma compounds evolved from the fruits. Then electronic nose sensor responses were categorized into the above maturity categories, and their effectiveness was determined using a statistical procedure called Discriminant Analysis (DA). From the DA cross validation results the correct classification percentage for Gala and York apples into maturity groups was 95%. The Electronic nose sensor's effectiveness to categorize the same observations based on sensor responses in to the above classified maturity categories was 83% correct in case Gala apples and 69% for York apples. The EN sensors response data were analyzed by the EN system software and the correct classification percentage for Gala was 83% and for York was 81%. Aroma-based categorization for Gala apples was 100% correct, while the electronic nose for the same analysis was 80%. Based on the three physical parameters, an objective evaluation of maturity could be accomplished. Principal Component Analysis, Canonical Discriminant Analysis and DA results demonstrated that the electronic nose could be used to classify apples into three identified maturity-based groups. The EN sensors (Gala apples), could also classify the apples into aroma-based categories. Thus, it can be concluded that the EN system holds promise as non-destructive evaluation technique to determine the maturity of an apple. / Master of Science
9

Effects of siRNA-squalene nanoparticles on RET/PTCs junction oncogenes in papillary thyroid carcinoma : from molecular and cellular studies to preclinical investigations / Effets des nanoparticules de siRNA-Squalène sur les oncogènes de jonction RET/PTCs dans le carcinome papillaire de la thyroïde : études moléculaires, cellulaires et investigations précliniques

Ali, Hafiz Muhammad 22 April 2014 (has links)
Le cancer papillaire de la thyroïde (PTC) est celui le plus fréquent de la thyroïde. Il est caractérisé par des réarrangements chromosomique affectant le gène RET, dont les plus fréquemment observés sont RET/PTC1 et RET/PTC3. Les oncogène de jonction sont spécifiques à la tumeur et représentent une cible privilégiée pour une thérapie ciblée par des petits ARN interférents (siRNA). Notre but est d’introduire une nouvelle approche pharmacologique par siRNA pour les PTC. Pour réaliser nos expériences, la lignée cellulaire humaine PTC, BHP10-3 SCmice exprimant l’oncogène RET/PTC1 a été utilisé. En absence de lignée RET/PTC3 commercialisée nous avons établi la lignée cellulaire RP3 (stablement transfecté la lignée NIH/3T3 issue de fibroblastes de souris par un vecteur d’expression RET/PTC3) qui s’est avérée tumorigène chez la souris. Ensuite, des siRNAs dirigés contre la jonction ont été dessinés. Les siRNAs ont été trouvés efficaces et spécifiques contre leurs propres oncogènes de jonction et ne sont pas capables d'inhiber l'expression de séquences alternées. Les siRNAs ont été vectorisés sous forme de nanoparticules (NPs) de squalène (SQ). In vitro, les NPs siRNA RET/PTC1-SQ et NPs siRNA RET/PTC3-SQ sont incapables d’inhiber l’expression de l’oncogène et l’oncoprotéine sauf transfectés par lipofectamine. Pour cela, un peptide, le GALA-Chol a été combiné aux NPs siRNA RET/PTC1-SQ ce qui les a rendu efficace in vitro dans l’inhibition de l’oncogène et de l’oncoprotéine mais inefficace sur la croissance tumorale in vivo probablement par agrégation des NPs siRNA RET/PTC1-SQ GALA-Chol dans la circulation sanguine. En revanche les NPs siRNA RET/PTC1-SQ (0.5mg/kg/souris) et NPs siRNA RET/PTC3-SQ (2.5mg/kg/souris) sont efficaces in vivo, ils inhibent considérablement la croissance tumorale, réduisent l’expression des oncogènes et des oncoprotéines RET/PTCs, induisent la mort cellulaire par clivage de la caspase-3 et de PARP-1 et restaurent partiellement la différenciation (diminution de marqueur Ki67). Ces résultats suggèrent l'utilisation des NPs siRNAs-SQ en tant que traitement pour les patients atteints de PTC exprimant les oncogènes de jonctions RET/PTCs. / Papillary thyroid carcinoma (PTC) is the most common of thyroid cancers. PTC is characterized by chromosomal rearrangements affecting chromosome 10 and leading to RET/PTC junction oncogenes. The most frequent ones are RET/PTC1 and RET/PTC3. Because the junction oncogenes are present only in the tumour cells, they represent a good target for a specific therapy such as small interfering RNA (siRNA). Our aim is to introduce a new pharmacological approach by siRNA for PTC. To perform the experiments, human BHP10-3 SCmice cell line expressing RET/PTC1 was used. Due to absence of commercially available RET/PTC3 cell line, we established a new RP3 cell line (from NIH/3T3 mouse fibroblasts, transfected stably with the RET/PTC3 expression vector) which was found to become tumorigenic in nude mice. siRNAs were designed within the junction sequences of both RET/PTC1 and RET/PTC3. Both siRNAs were found efficient and specific against their own junction oncogenes and were not able to inhibit the expression of alternate sequences. Then, siRNAs were vectorized in the form of nanoparticles (NPs) of squalene (SQ). In vitro, both siRNA RET/PTC1-SQ NPs and siRNA RET/PTC3-SQ NPs were found to be inefficient in gene and protein inhibitions except once transfected with lipofectamine. Therefore, a peptide GALA-Chol was added in siRNA RET/PTC1-SQ NPs which rendered them efficient in vitro in gene and protein inhibitions but found to be inefficient in vivo. The nanoparticles of siRNA RET/PTC1-SQ NPs (0.5 mg/kg/mouse) and siRNA RET/PTC3-SQ NPs (2.5 mg/kg/mouse) were found to drastically reduce the tumor growth and RET/PTCs oncogene and oncoprotein expressions. Moreover, they induced cell death by cleavage of both caspase-3 and PARP-1 and partially restored differentiation (decrease of Ki67 marker). Our findings highly support the use of siRNAs-SQ NPs as a treatment for patients affected by PTC expressing RET/PTCs.
10

Vectorisation de siRNA dirigés contre l'oncogène de fusion RET/PTC1 impliqué dans le carcinome papillaire de la thyroïde par des nanoparticules de squalène / Vectorization of siRNA targeting RET/PTC1 jonction oncogene by squalene nanoparticles

Raouane, Mouna 10 November 2011 (has links)
Le cancer papillaire de la thyroïde (PTC) représente 70-80% des cas de cancers de la thyroïde. Il est principalement caractérisé par des réarrangements chromosomiques affectant le gène RET. Le réarrangement RET/PTC1, dans lequel RET est réarrangé avec un gène proapoptotique H4, représente 30% des cas sporadiques et jusqu’à 60% des cas survenus après irradiation. Afin d’inhiber l’oncogène de fusion RET/PTC1, nous avons utilisé un siRNA ciblant la zone de jonction RET/PTC1 (siRNA RET/PTC1) au niveau de l’ARN messager des cellules tumorales et montré sa spécificité et son efficacité. Néanmoins, le développement des siRNAs comme molécule d’intérêt thérapeutique se heurte in vivo à des difficultés liées à leur administration. Sous forme libre, ces molécules sont, en effet, très vite dégradées par les nucléases extracellulaires et leur pénétration intracellulaire est limitée. C’est la raison pour laquelle il est nécessaire de les vectoriser. Nous avons choisi de le faire par la méthode de « squalénisation » et avons couplé d’une manière covalente le squalène, un lipide naturel précurseur de la biosynthèse du cholestérol, au siRNA RET/PTC1. Le bioconjugué formé s’autoassemble spontanément en milieu aqueux sous forme de nanoparticules stables de 170 nm de diamètre. L’efficacité et la toxicité des nanoparticules siRNA RET/PTC1-squalène ont été étudiées in vitro dans deux lignées de PTC exprimant RET/PTC1 (BHP10-3 et TPC-1) et l’activité antitumorale a été évaluée in vivo sur des souris athymiques xénogreffées par BHP10-3 puis traitées en i.v. par ces nanoparticules. Les nanoparticules siRNA RET/PTC1-squalène ont montré une bonne efficacité antitumorale. En revanche, aucune activité inhibitrice n’a été retrouvée in vitro. En conclusion, nous avons réussi à vectoriser le siRNA RET/PTC1 par la méthode de squalénisation. Cette étude ouvre des perspectives thérapeutiques pour certains patients atteints de PTC et réfractaires au traitement conventionnel. / The papillary thyroid carcinoma (PTC) is the most common type of thyroid malignancy. This tumour is associated with somatic mutations of the RET proto-oncogene, due to gene rearrangements of the proto-RET. RET/PTC1 rearrangement is the most common genetic alteration identified to date, it is formed by an intra chromosomic rearrangement which leads to the juxtaposition of the RET Tyrosine Kinase domain of the proto-RET with the gene H4. The fusion RET/PTC1 oncogene represents an interesting target for small interfering RNA (siRNA) strategies since it is present only in the tumour cells and not in the surrounding normal cells. However, the biological efficacy of the siRNAs is hampered by their short plasma half-life due to poor stability in biological fluids and low intracellular penetration. In order to protect siRNA from degradation, and to improve their intracellular capture, we applied the concept of “squalenoylation”, ie. The bioconjugation of a drug substance to squalene, for the delivery of siRNA targeted toward the RET/PTC1 fusion oncogene. The acyclic isoprenoid chain of squalene was covalently coupled with RET/PTC1 siRNA at the 3’-terminus of the sense strand via a stable thioether linkage. The linkage of RET/PTC1 siRNA to squalene leads to an amphiphilic molecule that self-organise in water as RET/PTC1 siRNA-SQ nanoassemblies of 170 nm and Zeta potential of -26.4 mV. These RET/PTC1 siRNA-SQ NPs did not showed any cytotoxicity in vitro. Interestingly, in vivo, in a mouse xenografted RET/PTC1 experimental model, RET/PTC1 siRNA-SQ nanoparticles inhibited tumour growth, RET/PTC1 oncogene and oncoprotein expression, after intravenous injections of 2.5 mg/kg cumulative dose. In the last of this work, GALA-cholesterol combination with siRNA-SQ NPs further enhanced nucleic acid internalization, promoted their escape into the cytosol and consequently their gene silencing efficiency in vitro. In conclusion, these results showed that the “squalenoylation” offers a new non cationic plate-form for the siRNA delivery.

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