subject:(616 1)

1. Zhang, Ke. Un microRNA dérivé de la séquence TAR du VIH-1 augmente l'expression des gènes viraux en activant le facteur de transcription cellulaire NF-kB : HIV-1 TAR derived microRNA regulates viral gene expression by modulating NF-κB transcription factor.

Degree: Docteur es, Biologie Santé, 2013, Université Montpellier I

URL: http://www.theses.fr/2013MON13504

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L'ARN d'interférence (ARNi) est un mécanisme de régulation du gène qui permet un ciblage spécifique d'ARNmessager (ARNm) par reconnaissance de séquence. Les effecteurs de l'ARNi… (more)

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L'ARN d'interférence (ARNi) est un mécanisme de régulation du gène qui permet un ciblage spécifique d'ARNmessager (ARNm) par reconnaissance de séquence. Les effecteurs de l'ARNi sont de petites molécules d'ARN non codants (siARN, microARN et piARN). Evoluant dans le contexte de l'ARNi, les virus de différentes familles ont adopté des stratégies afin utiliser l'ARNipour leur propre bénéfice. Le principal objectif de ma thèse a été d'étudier la fonction de l' ARNmiRTAR, un miARN viral dérivé de l'extrémité 3 'de l'ARN VIH-1 TAR dans la réplication du VIH-1. Nous avons constaté que miRTAR réguleà la fois l'activité basale et la transactivation induite par Tat du promoteur du VIH-1. L'effet de miRTAR ne nécessite pas de sa liaison à l'ARN TAR. miRTAR agit en augmentant l'activité de NF-kB, un facteur important pour la transcription du promoteur du VIH-1. En effet, la mutation des sites NF-kB, mais pas des sites Sp1 dans le LTR, abroge l'amélioration miRTARmédiée par la transcription. De plus, l'inhibition de l'expression de NF-kBpardes siARNspécifiquesdes les sous-unités p50 et p65, entraîne une perte d'activité dumiRTAR. Bien que nous n'avons pas pu identifier le(s) gène(s) cellulaire(s) ciblé par miRTAR, sa surexpression conduit à l'activation de la voie NF-kB. Mutation de l'extrémité 3 'du VIH-1 dans les résultats TAR réduction spectaculaire de la réplication virale Tat sans affecter médiée par la transcription, en raison de la perte de production de miRTARsauvage. Enfin, la surexpression de miRTARrestaure la réplication de ce virus contenant une mutation au niveau de la séquence TAR. En conclusion, nos résultats démontrent clairement que lemiRTARencodé par le VIH-1 joue un rôle clé dans la réplication du virus. Sur la base de ces résultats, nous proposons le modèle suivant pour la fonction de miRTAR. La transcription du LTR du VIH-1 conduit à la production de courts ARN dénommés TAR contenant une structure en épingle à cheveux. TAR est « processé » pour générer le miARN miRTAR. L'ARN miRTAR est ensuite chargé dans le complexe RISC et régule l'expression de plusieurs gènes cellulaires impliqués dans la régulation négative de NF-kB. miRTARmédiée par l'activation de NF-kB résultats dans la régulation de gènes viraux et par conséquent augmente la production de virus. L'ensemble de nos résultats montrent que le VIH-1 utilise la voie de l'ARNiinterférence pour optimiser l'environnement intracellulaire requis pour une réplication optimale.

RNA interference (RNAi) is a gene regulatory mechanism that offers a sequence specific targeting of mRNA. Evolving in the context of RNAi, viruses of different families adopted strategies to use RNAi for their benefit. The main objective of my thesis was to understand the function of miRTAR, a viral miRNA derived from 3' end of the HIV-1 TAR RNA, in HIV-1 replication. We found that miRTAR regulates both basal and Tat-mediated transactivation of HIV-1 promoter. The effect of miRTAR does not require its binding to TAR RNA. miRTAR acts by inducing NF-κB transcription factor important for…

Advisors/Committee Members: Benkirane, Monsef (thesis director).

Subjects/Keywords: Arn; Vih-1; Replication; Rna; Hiv-1; Replication; 616

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Zhang, K. (2013). Un microRNA dérivé de la séquence TAR du VIH-1 augmente l'expression des gènes viraux en activant le facteur de transcription cellulaire NF-kB : HIV-1 TAR derived microRNA regulates viral gene expression by modulating NF-κB transcription factor. (Doctoral Dissertation). Université Montpellier I. Retrieved from http://www.theses.fr/2013MON13504

Chicago Manual of Style (16^th Edition):

Zhang, Ke. “Un microRNA dérivé de la séquence TAR du VIH-1 augmente l'expression des gènes viraux en activant le facteur de transcription cellulaire NF-kB : HIV-1 TAR derived microRNA regulates viral gene expression by modulating NF-κB transcription factor.” 2013. Doctoral Dissertation, Université Montpellier I. Accessed March 01, 2021. http://www.theses.fr/2013MON13504.

MLA Handbook (7^th Edition):

Zhang, Ke. “Un microRNA dérivé de la séquence TAR du VIH-1 augmente l'expression des gènes viraux en activant le facteur de transcription cellulaire NF-kB : HIV-1 TAR derived microRNA regulates viral gene expression by modulating NF-κB transcription factor.” 2013. Web. 01 Mar 2021.

Vancouver:

Zhang K. Un microRNA dérivé de la séquence TAR du VIH-1 augmente l'expression des gènes viraux en activant le facteur de transcription cellulaire NF-kB : HIV-1 TAR derived microRNA regulates viral gene expression by modulating NF-κB transcription factor. [Internet] [Doctoral dissertation]. Université Montpellier I; 2013. [cited 2021 Mar 01]. Available from: http://www.theses.fr/2013MON13504.

Council of Science Editors:

Zhang K. Un microRNA dérivé de la séquence TAR du VIH-1 augmente l'expression des gènes viraux en activant le facteur de transcription cellulaire NF-kB : HIV-1 TAR derived microRNA regulates viral gene expression by modulating NF-κB transcription factor. [Doctoral Dissertation]. Université Montpellier I; 2013. Available from: http://www.theses.fr/2013MON13504

2. Laverdure, Sylvain. Régulation de la transcription bidirectionnelle chez le Virus de l'Immunodéficience Humaine de type 1 : Bidirectional transcription regulation in Human Immunodeficiency Virus type 1.

Degree: Docteur es, Biologie Santé, 2012, Université Montpellier I

URL: http://www.theses.fr/2012MON13514

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Le génome des rétrovirus existe sous deux formes différentes : sous forme d'ARN simple brin, qui est traduit ou encapsidé, ou sous forme d'ADN double… (more)

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Le génome des rétrovirus existe sous deux formes différentes : sous forme d'ARN simple brin, qui est traduit ou encapsidé, ou sous forme d'ADN double brin intégré dans le génome de la cellule hôte infectée. Cette dernière forme, l'ADN proviral, est indispensable à la production de tous les ARNm viraux nécessaires à la synthèse des protéines virales, qui en retour agissent sur la région promotrice située au niveau du LTR 5'. Cependant, l'ADN proviral possède un second LTR à son extrémité 3', capable de réguler une transcription antisens, orientée dans la direction opposée à celle contrôlée par le LTR 5'. L'ADN proviral a donc deux brins codants, ce qui offre au virus un plus grand potentiel de synthèse protéique. Dans le cas du Virus de l'immunodéficience Humaine de type 1 (VIH-1), la transcription antisens permet la production d'une protéine, appelée ASP (Antisense Protein). Dans ce manuscrit, nous démontrons que cette activité transcriptionnelle antisens s'exprime préférentiellement dans les cellules d'origine monocytaire, en particulier les cellules dendritiques ; une localisation membranaire de la protéine ASP a par ailleurs été mise en évidence dans ce type cellulaire. Nos résultats suggèrent également que la transcription antisens du VIH-1 est indépendante de la protéine Tat, et que par ailleurs les deux types de transcriptions ne sont pas exprimés simultanément au sein d'une même cellule. En outre, nos données soulignent que la séquence codante de la protéine ASP est très fortement conservée parmi les différents isolats viraux. Sur la base de l'ensemble de ces résultats, notre hypothèse est que la protéine ASP du VIH-1 possède des fonctions cruciales dans le cycle réplicatif des rétrovirus, indépendantes de la production virale.

Genome of retroviruses exists in two different forms: as single-stranded RNA that is translated or packaged, or as double-stranded DNA integrated into the genome of the infected host cell. The latter form, the proviral DNA, is essential for the production of all viral mRNAs required for the synthesis of viral proteins, which in turn act on the promoter region located at the 5 '-LTR. However, the proviral DNA has a second LTR at its 3 '-end, capable of regulating antisense transcription oriented in the opposite direction to that controlled by the 5'-LTR. The proviral DNA has then two coding strands, which gives the virus a greater potential for protein synthesis. In the case of the Human Immunodeficiency Virus type 1 (HIV-1), antisense transcription allows the production of a protein called ASP (Antisense Protein). In this manuscript, we demonstrate that this antisense transcriptional activity is preferentially expressed in cells of the monocyte lineage, in particular dendritic cells; a membrane localization of the ASP protein was also observed in this cell type. Our results also suggest that the antisense transcription of HIV-1 is Tat-independent, and what's more that the two types of transcription are not expressed simultaneously within the same cell. In addition, our data highlight…

Advisors/Committee Members: Mesnard, Jean-Michel (thesis director).

Subjects/Keywords: Vih-1; Transcription antisens; Asp; Cellules dendritiques; Rétrovirus; Htlv-1; Hiv-1; Antisense transcription; Asp; Dendritic cells; Retrovirus; Htlv-1; 616

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Laverdure, S. (2012). Régulation de la transcription bidirectionnelle chez le Virus de l'Immunodéficience Humaine de type 1 : Bidirectional transcription regulation in Human Immunodeficiency Virus type 1. (Doctoral Dissertation). Université Montpellier I. Retrieved from http://www.theses.fr/2012MON13514

Chicago Manual of Style (16^th Edition):

Laverdure, Sylvain. “Régulation de la transcription bidirectionnelle chez le Virus de l'Immunodéficience Humaine de type 1 : Bidirectional transcription regulation in Human Immunodeficiency Virus type 1.” 2012. Doctoral Dissertation, Université Montpellier I. Accessed March 01, 2021. http://www.theses.fr/2012MON13514.

MLA Handbook (7^th Edition):

Laverdure, Sylvain. “Régulation de la transcription bidirectionnelle chez le Virus de l'Immunodéficience Humaine de type 1 : Bidirectional transcription regulation in Human Immunodeficiency Virus type 1.” 2012. Web. 01 Mar 2021.

Vancouver:

Laverdure S. Régulation de la transcription bidirectionnelle chez le Virus de l'Immunodéficience Humaine de type 1 : Bidirectional transcription regulation in Human Immunodeficiency Virus type 1. [Internet] [Doctoral dissertation]. Université Montpellier I; 2012. [cited 2021 Mar 01]. Available from: http://www.theses.fr/2012MON13514.

Council of Science Editors:

Laverdure S. Régulation de la transcription bidirectionnelle chez le Virus de l'Immunodéficience Humaine de type 1 : Bidirectional transcription regulation in Human Immunodeficiency Virus type 1. [Doctoral Dissertation]. Université Montpellier I; 2012. Available from: http://www.theses.fr/2012MON13514

3. Borel, Sophie. Etude de l’interaction entre la protéine Vif du VIH-1 et la protéine LC3 impliquée dans le processus autophagique : Study of the interaction between the viral protein Vif and the LC3 protein involved in the autophagic process.

Degree: Docteur es, Biologie Santé, 2012, Université Montpellier I

URL: http://www.theses.fr/2012MON13518

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L'autophagie est un mécanisme de dégradation lysosomale qui joue un rôle important dans l'immunité innée et adaptative. La relation entre le Virus de l'Immunodéficience Humaine… (more)

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L'autophagie est un mécanisme de dégradation lysosomale qui joue un rôle important dans l'immunité innée et adaptative. La relation entre le Virus de l'Immunodéficience Humaine de type 1 (VIH-1) et l'autophagie est complexe. En effet, l'équipe a montré que l'enveloppe virale du VIH-1 (Env), exprimée à la surface des cellules infectées, induit une autophagie massive dans les cellules T CD4 bystanders non infectées. Au contraire, lorsque ces cellules s'infectent de façon productive, l'autophagie est inhibée, suggérant qu'une ou plusieurs protéines virales soient capables de bloquer ce processus. L'objectif de ce travail de thèse a été de rechercher ces protéines virales et leur mécanisme d'action. Un crible double hybride en levure a permis de mettre en évidence que plusieurs protéines du VIH-1 sont capables d'interagir avec des protéines autophagiques (Atg), et plus spécifiquement que la protéine virale Vif (Virion infectivity factor) interagit directement avec la protéine LC3, protéine essentielle au processus autophagique. Cette interaction a été confirmée en système in vitro et in vivo (GST pull-down et immunoprécipitation). Plusieurs mutants des protéines Vif et LC3 ont été réalisés pour déterminer les domaines de liaison. La partie C-terminale de Vif ainsi que la glycine C-terminale de LC3, responsable de la conjugaison au phosphatidylethanolamine (PE), semblent être les domaines impliqués dans cette interaction. Une des principales fonctions de Vif connues est de dégrader, via le protéasome, les facteurs cellulaires APOBEC (Apolipoprotein B mRNA-editing, enzyme-catalytic, polypeptide-like) et en particulier la protéine APOBEC3G (A3G). Les résultats montrent que Vif est impliquée dans le blocage de l'autophagie induite par l'enveloppe indépendamment de son action sur A3G.

Autophagy is a lysosomal degradation pathway involved in the innate and adaptative immunity. The relationship between the Human Immunodeficiency Virus type 1 (HIV-1) and autophagy is complex. The team has demonstrated that autophagy is induced in uninfected CD4 T cells after contact with infected cells expressing HIV-1 envelope glycoproteins (Env), leading to apoptosis. In contrast, when these cells are productively infected, autophagy is repressed, suggesting that one or several viral proteins are able to block this process. The aim of the thesis was to search these viral proteins and to determine their mechanism of action. A two-hybrid screen has revealed that several HIV-1 viral proteins are able to interact with autophagic proteins (Atg). In particular, Vif (Virion infectivity factor) interacts directly with LC3, a protein involved in the formation of autophagosomes. This interaction has been confirmed in vitro and in vivo (GST pull-down and immunoprecipitation). Several mutants of Vif and LC3 have been done to analyze the binding domains. The C-terminal part of Vif and the C-terminal glycine of LC3, responsible for the conjugation to PE, seem to be involved in the interaction between Vif and LC3.Vif plays an important role during HIV-1…

Advisors/Committee Members: Biard-Piechaczyk, Martine (thesis director), Espert, Lucile (thesis director).

Subjects/Keywords: Vih-1; Vif; Lc3; Autophagie; Interactions moléculaires; Hiv-1; Vif; Lc3; Autophagy; Molecular interactions; 616

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Borel, S. (2012). Etude de l’interaction entre la protéine Vif du VIH-1 et la protéine LC3 impliquée dans le processus autophagique : Study of the interaction between the viral protein Vif and the LC3 protein involved in the autophagic process. (Doctoral Dissertation). Université Montpellier I. Retrieved from http://www.theses.fr/2012MON13518

Chicago Manual of Style (16^th Edition):

Borel, Sophie. “Etude de l’interaction entre la protéine Vif du VIH-1 et la protéine LC3 impliquée dans le processus autophagique : Study of the interaction between the viral protein Vif and the LC3 protein involved in the autophagic process.” 2012. Doctoral Dissertation, Université Montpellier I. Accessed March 01, 2021. http://www.theses.fr/2012MON13518.

MLA Handbook (7^th Edition):

Borel, Sophie. “Etude de l’interaction entre la protéine Vif du VIH-1 et la protéine LC3 impliquée dans le processus autophagique : Study of the interaction between the viral protein Vif and the LC3 protein involved in the autophagic process.” 2012. Web. 01 Mar 2021.

Vancouver:

Borel S. Etude de l’interaction entre la protéine Vif du VIH-1 et la protéine LC3 impliquée dans le processus autophagique : Study of the interaction between the viral protein Vif and the LC3 protein involved in the autophagic process. [Internet] [Doctoral dissertation]. Université Montpellier I; 2012. [cited 2021 Mar 01]. Available from: http://www.theses.fr/2012MON13518.

Council of Science Editors:

Borel S. Etude de l’interaction entre la protéine Vif du VIH-1 et la protéine LC3 impliquée dans le processus autophagique : Study of the interaction between the viral protein Vif and the LC3 protein involved in the autophagic process. [Doctoral Dissertation]. Université Montpellier I; 2012. Available from: http://www.theses.fr/2012MON13518

4. Poupon, Laura. Etude des canaux ioniques TREK 1 et HCN dans la neuropathie chimio-induite à l'oxaliplatine. : Involvement of ionic channels, molecular targets for the development of new analgesics, in the treatment of the neuropathy induced by oxaliplatin-chemotherapy.

Degree: Docteur es, Sciences de la vie et de la sante, 2015, Clermont-Ferrand 1

URL: http://www.theses.fr/2015CLF1MM11

► L’oxaliplatine, anticancéreux utilisé en première intention dans le traitement du cancercolorectal, engendre des neuropathies qui se caractérisent par des dommages du systèmenerveux périphériques responsables de… (more)

▼ L’oxaliplatine, anticancéreux utilisé en première intention dans le traitement du cancercolorectal, engendre des neuropathies qui se caractérisent par des dommages du systèmenerveux périphériques responsables de l’apparition de troubles sensitifs douloureux dès lapremière cure ainsi que de troubles moteurs mais également des comorbidités qui s’installentavec la répétition des cures. Les traitements actuellement disponibles sont peu efficaces pourtraiter ces neuropathies qui sont à l’origine d’une altération de la qualité de vie des patients etpeuvent conduire à une diminution des doses de chimiothérapie utilisées voire même à l’arrêtdu traitement, compromettant ainsi les chances de guérison. Des données du laboratoire ont misen avant plusieurs canaux ioniques comme étant des cibles moléculaires potentielles pour letraitement de la neuropathie aigue. Le but de ce travail de thèse a été de poursuivre les étudespermettant de comprendre le mécanisme de survenue de ces effets indésirables et de rechercherles canaux dont la modulation pharmacologique permettrait un traitement efficace et bien tolérépour ces neuropathies.Pour se faire nous avons décidé de mieux caractériser un modèle murin de neuropathiedouloureuse aigue et de mettre au point et caractériser un modèle de neuropathie chroniqueinduites respectivement, par des injections unique ou répétées d’oxaliplatine. Un travailéthologique a été entrepris chez ces modèles afin d’évaluer la survenue et le suivi longitudinaldes symptômes retrouvés en clinique : symptômes douloureux céphaliques et extracéphaliques,déficits moteurs, dépression, anxiété. Chez ces mêmes animaux, des analyses moléculaires nousont permis de sélectionner des gènes codant pour des canaux ioniques impliqués dans laphysiologie et la pharmacologie de la douleur (canaux potassiques TREK et TRAAK, canauxHCN1 & HCN2). Nous avons parallèlement entrepris de valider pharmacologiquement ces cibleschez l’animal. Les résultats de nos travaux sont présentés séquentiellement et concernent :l’étude de l’implication des canaux HCN dans l’hypersensibilité douloureuse céphalique etextracéphalique induite par l’oxaliplatine ; l’étude de l’implication des canaux TREK et TRAAKdans la neuropathie chronique induite par l’oxaliplatine et la validation pharmacologique de cescibles chez un modèle murin de cancer colorectal.Dans un premier temps, nous avons utilisé un modèle de neuropathie aigue induit parune unique injection d’oxaliplatine (6mg/kg), et avons caractérisé les symptômes décrits enclinique au niveau du territoire céphalique. Nous avons observé l’existence de symptômesdouloureux au niveau orofacial et nous avons pu les corréler à une surexpression des canauxHCN1& HCN2. Il avait précédemment été démontré une surexpression de ses mêmes canaux auniveau extracéphalique, ce qui en fait des cibles particulièrement pertinentes compte tenu desdifférences anatomiques et pharmacologiques connues entre ces deux territoires somatiques. Deplus, l’utilisation d’ivabradine (Procoralan®), antagoniste non sélectif de ces canaux,… Advisors/Committee Members: Busserolles, Jérôme (thesis director).

Subjects/Keywords: Oxaliplatine; Neuropathie; TRECK-1; HCN; Riluzole; Ivabradine; Oxyloplatin; Neuropathy; TRECK-1; HCN; Riluzole; Ivabradine; 616

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Poupon, L. (2015). Etude des canaux ioniques TREK 1 et HCN dans la neuropathie chimio-induite à l'oxaliplatine. : Involvement of ionic channels, molecular targets for the development of new analgesics, in the treatment of the neuropathy induced by oxaliplatin-chemotherapy. (Doctoral Dissertation). Clermont-Ferrand 1. Retrieved from http://www.theses.fr/2015CLF1MM11

Chicago Manual of Style (16^th Edition):

Poupon, Laura. “Etude des canaux ioniques TREK 1 et HCN dans la neuropathie chimio-induite à l'oxaliplatine. : Involvement of ionic channels, molecular targets for the development of new analgesics, in the treatment of the neuropathy induced by oxaliplatin-chemotherapy.” 2015. Doctoral Dissertation, Clermont-Ferrand 1. Accessed March 01, 2021. http://www.theses.fr/2015CLF1MM11.

MLA Handbook (7^th Edition):

Poupon, Laura. “Etude des canaux ioniques TREK 1 et HCN dans la neuropathie chimio-induite à l'oxaliplatine. : Involvement of ionic channels, molecular targets for the development of new analgesics, in the treatment of the neuropathy induced by oxaliplatin-chemotherapy.” 2015. Web. 01 Mar 2021.

Vancouver:

Poupon L. Etude des canaux ioniques TREK 1 et HCN dans la neuropathie chimio-induite à l'oxaliplatine. : Involvement of ionic channels, molecular targets for the development of new analgesics, in the treatment of the neuropathy induced by oxaliplatin-chemotherapy. [Internet] [Doctoral dissertation]. Clermont-Ferrand 1; 2015. [cited 2021 Mar 01]. Available from: http://www.theses.fr/2015CLF1MM11.

Council of Science Editors:

Poupon L. Etude des canaux ioniques TREK 1 et HCN dans la neuropathie chimio-induite à l'oxaliplatine. : Involvement of ionic channels, molecular targets for the development of new analgesics, in the treatment of the neuropathy induced by oxaliplatin-chemotherapy. [Doctoral Dissertation]. Clermont-Ferrand 1; 2015. Available from: http://www.theses.fr/2015CLF1MM11

5. Dosil Garcia, Maria Alba. Estudi del paper d’E2F-1 i Ciclina D1 en tumors sòlids deficients per PTEN i avaluació de teràpies dirigides.

Degree: Departament de Ciències Mèdiques Bàsiques, 2018, Universitat de Lleida

URL: http://hdl.handle.net/10803/462062

► PTEN is one of the most frequently mutated genes in human cancers. A significant proportion of human malignancies present PTEN deficiency, such as endometrium, prostate,… (more)

▼ PTEN is one of the most frequently mutated genes in human cancers. A significant proportion of human malignancies present PTEN deficiency, such as endometrium, prostate, thyroid and colorectal carcinomas. Loss of PTEN leads to a dysregulation of cell cycle contributing to genomic instability, which is an important feature of the tumoral phenotype. For that reason, cell cycle proteins have been presented as key targets in the treatment of cancer. In this context, the transcription factor E2F-1 appears as intriguing protein because its dual function as oncogene and tumor suppressor gene depending on tissue-context. The clinical relevance and implication of E2F-1 expression in tumoral processes remain largely unknown at present time. Therefore, in the first part of this work, we have studied the role of E2F-1 in PTEN deficient tumors in vivo. Ablation of both genes does not affect the progression of endometrial, prostate and thyroid malignancies. However, surprisingly, monoallelic and biallelic deletion of E2F-1 induces an increment of the incidence and progression of colonic tumorigenesis driven by PTEN loss. In addition, absence of E2F-1 increases the number and the size of the colonic lesions. In the context of cell cycle regulation, it has been also described that PTEN controls the expression of Cyclin D1 through various mechanisms. Furthermore, PTEN deficiency promotes the accumulation of cell cycle complexes, such as Cyclin D1-CDK4/6. In the second part of this work, we have assessed the antitumoral effects of Cyclin D1 ablation in PTEN-induced malignancies in vivo. We have observed that Cyclin D1 loss triggers shrinkage of PTEN deficient endometrial neoplasias, but not on thyroid hyperplasias and prostate carcinomas. Finally, we have evaluated the therapeutic potential of two different inhibitors in endometrial, prostate and thyroid neoplasias induced by PTEN loss. First, and in accordance with previous results, inhibition of CDK4/6 with Palbociclib treatment only reduces the extent of PTEN-induced endometrial carcinoma in vivo, without affecting the progression of thyroid hyperplasias and prostate neoplasias. On the other hand, treatment with multikinase inhibitor Regorafenib was effective reducing thyroid lesions, but not endometrial and prostate neoplasms. While both drugs, Palbociclib and Regorafenib, slow down tumors progression, none of them eliminated the disease. Advisors/Committee Members: [email protected] (authoremail), false (authoremailshow), Matias-Guiu, Xavier (director), Dolcet Roca, Xavier (director), false (authorsendemail).

Subjects/Keywords: Càncer; PTEN; E2F-1; Palbociclib; Regorafenib; Cáncer; Cancer; Anatomia Patològica; 616

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Dosil Garcia, M. A. (2018). Estudi del paper d’E2F-1 i Ciclina D1 en tumors sòlids deficients per PTEN i avaluació de teràpies dirigides. (Thesis). Universitat de Lleida. Retrieved from http://hdl.handle.net/10803/462062

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Dosil Garcia, Maria Alba. “Estudi del paper d’E2F-1 i Ciclina D1 en tumors sòlids deficients per PTEN i avaluació de teràpies dirigides.” 2018. Thesis, Universitat de Lleida. Accessed March 01, 2021. http://hdl.handle.net/10803/462062.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Dosil Garcia, Maria Alba. “Estudi del paper d’E2F-1 i Ciclina D1 en tumors sòlids deficients per PTEN i avaluació de teràpies dirigides.” 2018. Web. 01 Mar 2021.

Vancouver:

Dosil Garcia MA. Estudi del paper d’E2F-1 i Ciclina D1 en tumors sòlids deficients per PTEN i avaluació de teràpies dirigides. [Internet] [Thesis]. Universitat de Lleida; 2018. [cited 2021 Mar 01]. Available from: http://hdl.handle.net/10803/462062.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Dosil Garcia MA. Estudi del paper d’E2F-1 i Ciclina D1 en tumors sòlids deficients per PTEN i avaluació de teràpies dirigides. [Thesis]. Universitat de Lleida; 2018. Available from: http://hdl.handle.net/10803/462062

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Plymouth

6. Abd Al-Sahib, Hanady. An investigation of the mechanism(s) of hyperoxia-induced cilial epithelial loss in mammalian bronchial tissue.

Degree: PhD, 2013, University of Plymouth

URL: http://hdl.handle.net/10026.1/1613

► Hyperoxia is an essential aid to life support in patients with severe respiratory failure. However, it is recognised as a contributor to the pathological consequences… (more)

▼ Hyperoxia is an essential aid to life support in patients with severe respiratory failure. However, it is recognised as a contributor to the pathological consequences of oxidative stress including oxidative tissue damage, inflammation and cell death resulting in acute or chronic lung injury. The specific mechanisms behind this type of injury are still not completely understood. This study was undertaken with two main aims. Firstly, to evaluate the adverse effects of hyperoxia on the ciliary coverage using a novel large animal model. For the first time, an in vitro bronchus bovine tissue culture model was developed and used to quantify ciliary coverage loss over time. The protection role of antioxidant supplementation with α-tocopherol and ascorbate was also investigated. Secondly, the importance of the tight junction protein ZO-1 in hyperoxia-induced monolayer permeability was investigated using a human bronchial cell line (16HBE14o-) and the potential inflammation effects on bronchial tightness. Additionally studies were carried out in order to find out if antioxidant vitamin treatment can protect against or reduce these effects. Scanning electronic microscopy indicated that hyperoxia caused a time dependent decline (t½ = 3.4 d compared to 37.1 d under normoxia) in ciliary coverage (P < 0.0001). This was associated with an increase in the number of sloughed cells, many apparently intact, into the medium (p < 0.05). Several biochemical parameters were assessed to obtain evidence of oxidative stress caused by hyperoxia in this model including tissue damage (lactate dehydrogenase, LDH, in the medium), lipid peroxidation (thiobarbituric acid reactive substances, TBARS), DNA damage (comet assay used for the first time with primary bronchus culture), protein oxidation (OxyBlot kit) and antioxidant status (total glutathione). Antioxidant vitamins had a significant protective effect on the hyperoxia-induced reduction in percentage ciliary coverage (P < 0.05). Moreover, an increase in the bronchial permeability was shown characterised by a significant decrease (P < 0.05) in transepithelial electrical resistance (TER) under hyperoxic conditions. The reduction of ZO-1 associated fluorescence (P < 0.01) is in compatible with the downregulation of ZO-1 expression assessed by RT-PCR. Levels of the pro-inflammatory cytokines IL-8, IL-6 and TNF-a concentration in the medium, as measured by ELISA, increased significantly (P < 0.001) under hyperoxia, and this was accompanied with a marked increase in the cytokine expression. However, the antioxidant vitamins E and C, partially reduced the impact effects of hyperoxia, both individually and in combination, whilst increases in ZO-1 expression and fluorescence intensity (P < 0.05), as well as the suppression of cytokine secretion and gene expression was modest. Use of these vitamins was not enough to reduce the epithelial permeability significantly compared to normoxia. The data implies that hyperoxia-induced damage to cultured bovine bronchial epithelium and the denudation of cilia over…

Subjects/Keywords: 616; Hyperoxia, oxidative stress, cilia, zona occludens-1

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APA (6^th Edition):

Abd Al-Sahib, H. (2013). An investigation of the mechanism(s) of hyperoxia-induced cilial epithelial loss in mammalian bronchial tissue. (Doctoral Dissertation). University of Plymouth. Retrieved from http://hdl.handle.net/10026.1/1613

Chicago Manual of Style (16^th Edition):

Abd Al-Sahib, Hanady. “An investigation of the mechanism(s) of hyperoxia-induced cilial epithelial loss in mammalian bronchial tissue.” 2013. Doctoral Dissertation, University of Plymouth. Accessed March 01, 2021. http://hdl.handle.net/10026.1/1613.

MLA Handbook (7^th Edition):

Abd Al-Sahib, Hanady. “An investigation of the mechanism(s) of hyperoxia-induced cilial epithelial loss in mammalian bronchial tissue.” 2013. Web. 01 Mar 2021.

Vancouver:

Abd Al-Sahib H. An investigation of the mechanism(s) of hyperoxia-induced cilial epithelial loss in mammalian bronchial tissue. [Internet] [Doctoral dissertation]. University of Plymouth; 2013. [cited 2021 Mar 01]. Available from: http://hdl.handle.net/10026.1/1613.

Council of Science Editors:

Abd Al-Sahib H. An investigation of the mechanism(s) of hyperoxia-induced cilial epithelial loss in mammalian bronchial tissue. [Doctoral Dissertation]. University of Plymouth; 2013. Available from: http://hdl.handle.net/10026.1/1613

University of Dundee

7. Vella, Sandro. Pharmacological modulation of insulin resistance : benefits and harms.

Degree: Thesis (M.D.), 2013, University of Dundee

URL: https://discovery.dundee.ac.uk/en/studentTheses/4428eca5-5018-4816-95d0-30c0a3043409 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.620763

► Aims: Thiazolidinediones have been advocated as second or third line insulin sensitizing agents in the management of type 2 diabetes (T2DM). Their widespread use has… (more)

▼ Aims: Thiazolidinediones have been advocated as second or third line insulin sensitizing agents in the management of type 2 diabetes (T2DM). Their widespread use has been hampered by concerns about their cardiovascular safety, including fluid retention. Metformin is established as first-line glucose-lowering pharmacotherapy in T2DM. It has also been suggested that it may have benefits in alleviating insulin resistance in type 1 diabetes (T1DM). This thesis examined: (i) cardiovascular, renal and metabolic differences between individuals with T2DM ‘tolerant’ or ‘intolerant’ of TZDs; (ii) risk factors for TZD-associated oedema in T2DM; and (iii) the potential for metformin as adjunct therapy in T1DM. Methods: (i) A small clinical study characterising TZD tolerant and intolerant individuals with T2DM; (ii) A population-based epidemiological study of TZD induced oedema in individuals with T2DM in Tayside, Scotland (using incident loop diuretic prescription as a surrogate); (iii) A systematic review and meta-analysis of published studies of adjunct metformin in T1DM. Results (i) During a five-day high sodium diet, two known TZD-intolerant individuals with T2DM had reductions in haematocrit, aldosterone, and diastolic BP and increases in ANP and central and peripheral augmentation indices which were outwith reference ranges derived from nine TZD-tolerant individuals; (ii) Predictors of time to loop diuretic prescription included age, body mass index, systolic BP, haematocrit, ALT and macrovascular disease but rates of this outcome did not differ by therapy: 4.3% (TZDs) vs 4.7% (other agents) [unadjusted OR 0.909 (95% CI 0.690, 1.196); p = 0.493]; (iii) In meta-analysis of nine small studies in T1DM (192.8 patient-years of follow-up), metformin was associated with a reduction in total daily insulin dose (6.6 units/day; p < 0.001) but no studies examined cardiovascular surrogates or outcomes. Conclusions: Hypotheses were generated for several potential biomarkers predictive of TZD-induced oedema but the clinical importance of TZDs as a risk factor for oedema in individuals with T2DM was questioned. As there is some evidence for the safety of metformin as an adjunct therapy in T1DM but little evidence of efficacy, larger studies are warranted.

Subjects/Keywords: 616; Thiazolidinediones; Metformin; Type 2 diabetes; Type 1 diabetes; Oedema; Heart failure

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APA (6^th Edition):

Vella, S. (2013). Pharmacological modulation of insulin resistance : benefits and harms. (Doctoral Dissertation). University of Dundee. Retrieved from https://discovery.dundee.ac.uk/en/studentTheses/4428eca5-5018-4816-95d0-30c0a3043409 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.620763

Chicago Manual of Style (16^th Edition):

Vella, Sandro. “Pharmacological modulation of insulin resistance : benefits and harms.” 2013. Doctoral Dissertation, University of Dundee. Accessed March 01, 2021. https://discovery.dundee.ac.uk/en/studentTheses/4428eca5-5018-4816-95d0-30c0a3043409 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.620763.

MLA Handbook (7^th Edition):

Vella, Sandro. “Pharmacological modulation of insulin resistance : benefits and harms.” 2013. Web. 01 Mar 2021.

Vancouver:

Vella S. Pharmacological modulation of insulin resistance : benefits and harms. [Internet] [Doctoral dissertation]. University of Dundee; 2013. [cited 2021 Mar 01]. Available from: https://discovery.dundee.ac.uk/en/studentTheses/4428eca5-5018-4816-95d0-30c0a3043409 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.620763.

Council of Science Editors:

Vella S. Pharmacological modulation of insulin resistance : benefits and harms. [Doctoral Dissertation]. University of Dundee; 2013. Available from: https://discovery.dundee.ac.uk/en/studentTheses/4428eca5-5018-4816-95d0-30c0a3043409 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.620763

8. Lemaçon, Delphine. Impact de l'haploinsuffisance d'ATR/CHK1 et de la Topoisomérase 1 sur la réplication et les Sites Fragiles Communs. : Impact of ATR/CHK1 haploinsufficiencies and Topoisomerase 1 on replication and Common Fragile Sites induction.

Degree: Docteur es, Biologie Santé, 2014, Université Montpellier I

URL: http://www.theses.fr/2014MON13502

►

Les Sites Fragiles Communs (SFCs) sont des points de cassures chromosomiques récurrents survenant suite à un stress réplicatif. La majorité d'entre eux ont été identifiés… (more)

▼

Les Sites Fragiles Communs (SFCs) sont des points de cassures chromosomiques récurrents survenant suite à un stress réplicatif. La majorité d'entre eux ont été identifiés suite à un traitement à l'Aphidicoline (APC), un inhibiteur des ADN polymérases, ce qui explique pourquoi l'étude de leur fragilité est majoritairement basée sur des perturbations de la réplication. Parmi les facteurs impliqués dans la fragilité, ATR (Ataxia Telangiectasia and Rad3 Related), une kinase engagée dans la signalisation des fourches de réplication bloquées, et sa cible CHK1 (Checkpoint Kinase 1), induisent l'apparition de cassures aux SFCs lorsqu'ils sont déplétés dans la cellule. Cependant, ces gènes sont difficiles à étudier car leur déplétion totale est létale pour les cellules. Nous avons donc choisi de développer un modèle basé sur l'utilisation de la lignée MSI de cancer colorectal HCT116de laquelle nous avons isolé des clones haploinsuffisants pour ATR ou CHK1.Ces mutations sont naturelles et sont d'ailleurs dans les cancers MSI. Aujourd'hui, de nouvelles données montrent que la transcription semble aussi être impliquée dans l'induction de certains SFCs. Pour étudier ce mécanisme, nous nous sommes servis de cellules déficientes pour la Topoisomérase 1 (Topo1) grâce à un shARN inductible. Cette protéine est impliquée dans la gestion des interférences entre les machineries de réplication et de transcription et son inhibition est à l'origine d'une forte instabilité chromosomique.Nos études démontrent tout d'abord que l'haploinsuffisance d'ATR ou de CHK1 retrouvée dans les cancers MSI génère des défauts de réplication, des problèmes de checkpoints ainsi que des cassures ADN et en particulier au niveau des SFCs. Une déficience en Topo1 induit aussi l'apparition de problèmes de réplication et une plus grande fragilité ADN, mais elle est aussi capable d'induire des cassures au niveau de certains SFCs, connus pour être sensible à des défauts de réplication. Une étude plus approfondie du SFC le plus fréquemment induit, FRA3B, montre qu'il est sensible à la fois à des défauts dans la voie ATR/CHK1, au stress réplicatif induits par l'aphidicoline mais aussi à la déficience en Topo1. Nos travaux suggèrent que l'haploinsuffisance d'ATR et CHK1 peut favoriser la cancérogenèse à travers l'induction des SFCs et que tous les SFCs n'ont pas les mêmes mécanismes d'induction, laissant la porte ouverte pour l’identification de nouveaux SFCs.

Common Fragile Sites (CFSs) are recurrent chromosomal breakpoints occurring when cells are exposed to replicative stress. Most CFSs have been identified following Aphidicolin (APC) treatment, an inhibitor of DNA polymerase and therefore the working model to explain their fragility is indeed mainly based on perturbation of replication. Among the key actors involved in fragility, ATR (Ataxia Telangiectasia and Rad3 Related), a kinase involved in stalled replication fork signaling, and its target CHK1 (Checkpoint Kinase 1), lead to enhanced chromosome fragility when transiently depleted in cells. However, ATR and…

Advisors/Committee Members: Coquelle, Arnaud (thesis director).

Subjects/Keywords: Atr; Chk1; Topoisomérase 1; Réplication; Sites Fragiles; Cancer; Atr; Chk1; Topoisomerase 1; Replication; Fragile Sites; Cancer; 616

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Lemaçon, D. (2014). Impact de l'haploinsuffisance d'ATR/CHK1 et de la Topoisomérase 1 sur la réplication et les Sites Fragiles Communs. : Impact of ATR/CHK1 haploinsufficiencies and Topoisomerase 1 on replication and Common Fragile Sites induction. (Doctoral Dissertation). Université Montpellier I. Retrieved from http://www.theses.fr/2014MON13502

Chicago Manual of Style (16^th Edition):

Lemaçon, Delphine. “Impact de l'haploinsuffisance d'ATR/CHK1 et de la Topoisomérase 1 sur la réplication et les Sites Fragiles Communs. : Impact of ATR/CHK1 haploinsufficiencies and Topoisomerase 1 on replication and Common Fragile Sites induction.” 2014. Doctoral Dissertation, Université Montpellier I. Accessed March 01, 2021. http://www.theses.fr/2014MON13502.

MLA Handbook (7^th Edition):

Lemaçon, Delphine. “Impact de l'haploinsuffisance d'ATR/CHK1 et de la Topoisomérase 1 sur la réplication et les Sites Fragiles Communs. : Impact of ATR/CHK1 haploinsufficiencies and Topoisomerase 1 on replication and Common Fragile Sites induction.” 2014. Web. 01 Mar 2021.

Vancouver:

Lemaçon D. Impact de l'haploinsuffisance d'ATR/CHK1 et de la Topoisomérase 1 sur la réplication et les Sites Fragiles Communs. : Impact of ATR/CHK1 haploinsufficiencies and Topoisomerase 1 on replication and Common Fragile Sites induction. [Internet] [Doctoral dissertation]. Université Montpellier I; 2014. [cited 2021 Mar 01]. Available from: http://www.theses.fr/2014MON13502.

Council of Science Editors:

Lemaçon D. Impact de l'haploinsuffisance d'ATR/CHK1 et de la Topoisomérase 1 sur la réplication et les Sites Fragiles Communs. : Impact of ATR/CHK1 haploinsufficiencies and Topoisomerase 1 on replication and Common Fragile Sites induction. [Doctoral Dissertation]. Université Montpellier I; 2014. Available from: http://www.theses.fr/2014MON13502

Universitat Autònoma de Barcelona

9. Mateo Lozano, Silvia. Sarcoma de Ewing: nuevas aproximaciones terapéuticas y búsqueda de dianas biológicas del oncogén EWS/FLI-1.

Degree: Departament de Bioquímica i Biologia Molecular, 2007, Universitat Autònoma de Barcelona

URL: http://hdl.handle.net/10803/3571

► La familia de tumores del sarcoma de Ewing (ESFT) incluye un grupo heterogéneo de neoplasias caracterizadas por la presencia de células redondas de pequeño tamaño… (more)

▼ La familia de tumores del sarcoma de Ewing (ESFT) incluye un grupo heterogéneo de neoplasias caracterizadas por la presencia de células redondas de pequeño tamaño con mínima evidencia morfológica de diferenciación. ESFT es el segundo tumor óseo más frecuente, afectando fundamentalmente a niños y adolescentes. A pesar del uso de terapias agresivas combinando quimioterapia, radioterapia y cirugía, la supervivencia de pacientes con metástasis es aproximadamente del 30%, mientras que en ausencia de enfermedad metastásica alcanza valores del 70 %. Debido a esto, son necesarias nuevas aproximaciones terapéuticas dirigidas a reducir la morbilidad relacionada con el tratamiento y a mejorar el índice de supervivencia. Afortunadamente, los ESFT presentan una diana molecular perfecta que resulta de la translocación cromosómica t(11;22)(q24;q12), que ocurre en aproximadamente un 95% de los casos, e involucra al gen EWS y a un miembro de la familia de factores de transcripción ETS, fundamentalmente FLI-1 o ERG. La translocación más común genera la formación de la oncoproteína de fusión EWS/FLI-1 que actúa como factor de transcripción y regula de forma aberrante la expresión de genes diana, favoreciendo el proceso tumorigénico. De esta forma la inactivación de la proteína de fusión EWS/FLI-1 se convierte en una estrategia atractiva, no sólo debido su papel fundamental en la tumorigénesis de ESFT, sino también por su especificidad en células transformadas. En este estudio se evaluaron diferentes estrategias dirigidas a reducir los niveles expresión de EWS/FLI-1 in vitro e in vivo. La primera estrategia utilizada para inhibir los niveles de expresión de la proteína de fusión EWS/FLI-1 se basó en el uso de la rapamicina, un antifúngico e inmunosupresor con propiedades anticancerígenas. La rapamicina inhibió la vía de señalización de mTOR/p70s6K y la proliferación de células de ESFT. Estos resultados sugirieron el uso de esta droga como agente citostático en el tratamiento de este tipo de tumores. La segunda aproximación terapéutica se basó en la inhibición simultánea de EWS/FLI-1 a nivel transcripcional y post-transcripcional. El tratamiento combinado de oligonucleótidos antisentido y rapamicina resultó en un incremento en la muerte de células de ESFT, a través de un proceso que involucra la restauración de la vía de señalización pro-apoptótica del TGF?1/TGF?-RII. In vivo, la administración del tratamiento combinado causó un retraso en el crecimiento de los tumores. Estos datos aportan la base para una mayor exploración del potencial del tratamiento combinado como una nueva estrategia en el tratamiento de este tipo de tumores. Los análisis moleculares mostraron que ESFT presentan alteraciones en proteínas reguladoras del ciclo celular, incluyendo la sobreexpresión de proteínas quinasas ciclina-dependientes (CDK2) y la pérdida o baja expresión de sus inhibidores. Basándonos en ésto, la tercera estrategia se basó en la reversión de alguna de estas alteraciones, mediante el uso de la roscovitina, un potente inhibidor de la actividad… Advisors/Committee Members: [email protected] (authoremail), true (authoremailshow), Martínez Tirado, Òscar (codirector), Notario Ruiz, Vicente (codirector).

Subjects/Keywords: Rapamicina; Caveolina-1; EWS/FLI-1; Ciències Experimentals; 616

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Mateo Lozano, S. (2007). Sarcoma de Ewing: nuevas aproximaciones terapéuticas y búsqueda de dianas biológicas del oncogén EWS/FLI-1. (Thesis). Universitat Autònoma de Barcelona. Retrieved from http://hdl.handle.net/10803/3571

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Mateo Lozano, Silvia. “Sarcoma de Ewing: nuevas aproximaciones terapéuticas y búsqueda de dianas biológicas del oncogén EWS/FLI-1.” 2007. Thesis, Universitat Autònoma de Barcelona. Accessed March 01, 2021. http://hdl.handle.net/10803/3571.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Mateo Lozano, Silvia. “Sarcoma de Ewing: nuevas aproximaciones terapéuticas y búsqueda de dianas biológicas del oncogén EWS/FLI-1.” 2007. Web. 01 Mar 2021.

Vancouver:

Mateo Lozano S. Sarcoma de Ewing: nuevas aproximaciones terapéuticas y búsqueda de dianas biológicas del oncogén EWS/FLI-1. [Internet] [Thesis]. Universitat Autònoma de Barcelona; 2007. [cited 2021 Mar 01]. Available from: http://hdl.handle.net/10803/3571.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Mateo Lozano S. Sarcoma de Ewing: nuevas aproximaciones terapéuticas y búsqueda de dianas biológicas del oncogén EWS/FLI-1. [Thesis]. Universitat Autònoma de Barcelona; 2007. Available from: http://hdl.handle.net/10803/3571

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

10. Isambert, Nicolas. Etude des mécanismes d'action d'une immunothérapie par un triacyl lipide A chez l'homme : Study of mechanisms of action of an immunotherapy by triacyl lipid A in humans.

Degree: Docteur es, Médecine, 2013, Université de Bourgogne

URL: http://www.theses.fr/2013DIJOMU03

►

L’immunothérapie en agissant au niveau de la tumeur primitive et en empêchant le développement des métastases constitue une des stratégies du traitement des patients atteints… (more)

▼

L’immunothérapie en agissant au niveau de la tumeur primitive et en empêchant le développement des métastases constitue une des stratégies du traitement des patients atteints de cancer. Afin d’améliorer l’efficacité de celle-ci, il est nécessaire de comprendre comment est induit la mort des cellules tumorales. Dans le laboratoire, il a été observé la guérison de rats BDIX porteurs de tumeurs PROb par un triacyl lipide A. Il a été montré que cet effet impliquait le système immunitaire en mettant en jeu des interactions avec les TLR présents sur de nombreuses cellules tumorales et de l’immunité innée comme les neutrophiles.Dans ce travail, nous avons étudié l’implication éventuelle des neutrophiles dans l’activité anti tumorale du triacyl lipide A chez l’homme.Dans une étude de phase 1 chez des patients porteurs de tumeurs solides réfractaires, nous avons montré que le triacyl lipide A était bien toléré et qu’il induisait la sécrétion de cytokines impliquées dans la réponse immunitaire et notamment dans le recrutement des neutrophiles. Nous avons ensuite, dans un second temps démontré l’implication éventuelle des neutrophiles dans cette réponse immunitaire en vérifiant leur présence dans des tumeurs coliques humaines et en analysant leur proximité avec les cellules tumorales, ces deux facteurs déterminant leur cytotoxicité vis-à-vis des cellules tumorales. Nous avons ensuite fait une analyse comparative par rapport au tissu sain pour rechercher si ces neutrophiles étaient activés et comparer l’expression de chimio attractants.

Immunotherapy acting at the primary tumor site and preventing the development of metastases is one of the strategies for treatment of patients with cancer. To improve the efficiency of the latter, it is necessary to understand how it induces tumor cell death. In the laboratory, it was observed the cure of PROb tumors in rats BDIX by the triacyl lipid A. It has been shown that this effect involved the immune system involving interactions with TLRs present in many tumor cells and innate immunity cells such as neutrophils.In this work, we investigated the possible involvement of neutrophils in the antitumor activity of triacyl lipid A in humans.In a Phase 1 study in patients with refractory solid tumors, we showed that the triacyl lipid A was well tolerated and induced the secretion of cytokines involved in the immune response, particularly in the recruitment of neutrophils. Then, in a second part, we demonstrated the prospective involvement of neutrophils in the immune response by checking their presence in human colon cancers and analyzing their proximity to tumor cells, these two factors determining their cytotoxicity to cells tumor. Then we made a comparative analysis with healthy tissue to research whether these neutrophils were activated and compare the expression of chemo attractors.

Advisors/Committee Members: Jeannin, Jean-François (thesis director), Fumoleau, Pierre (thesis director).

Subjects/Keywords: Cancer; Immunothérapie; Triacyl lipide A; Phase 1; Polynucléaires neutrophiles; Granzyme B; Chimio attractants; No english keyword; 616.9; 571.9; 616

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Isambert, N. (2013). Etude des mécanismes d'action d'une immunothérapie par un triacyl lipide A chez l'homme : Study of mechanisms of action of an immunotherapy by triacyl lipid A in humans. (Doctoral Dissertation). Université de Bourgogne. Retrieved from http://www.theses.fr/2013DIJOMU03

Chicago Manual of Style (16^th Edition):

Isambert, Nicolas. “Etude des mécanismes d'action d'une immunothérapie par un triacyl lipide A chez l'homme : Study of mechanisms of action of an immunotherapy by triacyl lipid A in humans.” 2013. Doctoral Dissertation, Université de Bourgogne. Accessed March 01, 2021. http://www.theses.fr/2013DIJOMU03.

MLA Handbook (7^th Edition):

Isambert, Nicolas. “Etude des mécanismes d'action d'une immunothérapie par un triacyl lipide A chez l'homme : Study of mechanisms of action of an immunotherapy by triacyl lipid A in humans.” 2013. Web. 01 Mar 2021.

Vancouver:

Isambert N. Etude des mécanismes d'action d'une immunothérapie par un triacyl lipide A chez l'homme : Study of mechanisms of action of an immunotherapy by triacyl lipid A in humans. [Internet] [Doctoral dissertation]. Université de Bourgogne; 2013. [cited 2021 Mar 01]. Available from: http://www.theses.fr/2013DIJOMU03.

Council of Science Editors:

Isambert N. Etude des mécanismes d'action d'une immunothérapie par un triacyl lipide A chez l'homme : Study of mechanisms of action of an immunotherapy by triacyl lipid A in humans. [Doctoral Dissertation]. Université de Bourgogne; 2013. Available from: http://www.theses.fr/2013DIJOMU03

Universitat Autònoma de Barcelona

11. Puertas Castro, Mª Carmen. Caracterización fenotípica y funcional de los linfocitos B infiltrantes en islotes pancreáticos en ratones NOD. Identificación del antígeno neuroendocriono reconocido predominantemente por esta población celular.

Degree: Departament de Biologia Cel·lular i de Fisiologia, 2006, Universitat Autònoma de Barcelona

URL: http://hdl.handle.net/10803/3782

► Type 1 diabetes (T1D) is a complex autoimmune disease characterized by selective destruction of pancreatic beta cells by the patient's own immune system. Currently, one… (more)

▼ Type 1 diabetes (T1D) is a complex autoimmune disease characterized by selective destruction of pancreatic beta cells by the patient's own immune system. Currently, one of the best animal models of type 1 diabetes is the nonobese diabetic (NOD) mouse. NOD mice spontaneously develop a form of diabetes that closely resembles human type 1 diabetes. Islet-infiltrating T-cells are major effectors of beta-cell damage in T1D, however, other cellular elements of the immune system also play a critical role in the initiation and/or progression of T1D. Among these, B-cells are also recruited to pancreatic islets, during disease development. We hypothesize that islet-infiltrating B-cells may have distinctive functional traits, enabling them to regulate autoreactive T-cell activity in situ. The aim of the present study was the phenotypical and functional characterization of islet-infiltrating B cells, in T1D susceptible/resistant T1D murine models. Thus, it was observed that B-cell recruitment into pancreatic islets is higher in female mice, specially just before diabetes onset. Although they are mature B-cells, they interestingly show an abnormal down-regulation of surface CD19 expression, showing a possible hiporesponsive status of these cells, given the relevance of CD19 in regulating BCR activation. Islet-infiltrating B-cells develop a pronounced costimulator phenotype after in vitro stimulation with anti-CD40, thus revealing to be somehow repressed while in the islets. These results suggest that these B-cells, although not presenting immunoglobin class switch recombination, seem to be antigen-experienced. On the other hand, cytokine expression profile (IL-4, IFN?, IL-10) and T-cell activator quality of islet-infiltrating B-cells have been shown to be similar to that from their splenic counterparts. On the other hand, the second objective of this study was the identification of the autoantigen predominantly targeted by islet-infiltrating B-cells. In a previous study in our laboratory, antibody-producing hybridomas were generated from islet-infiltrating C-cells, and it was shown that most of them targeted peripheral nervous elements. In the present study, the isolation and subsequent molecular characterization of the antigen recognized by 21 of these monoclonal antibodies, proved that peripherin is the protein targeted by them all. This neuroendocrine autoantigen is a cytoskeleton protein mainly expressed by peripheral nervous cells, but it is also expressed, although at lower levels, by islet beta-cells. These data support the hypothesis that T1D autoimmune attack is not exclusively focused on pancreatic beta-cells, and that pancreatic nervous system damage may be involved in disease development. Advisors/Committee Members: [email protected] (authoremail), true (authoremailshow), Verdaguer Autonell, Joan (director).

Subjects/Keywords: Autoantígeno; Linfocito B; Diabetes tipo 1; Ciències Experimentals; 616

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Puertas Castro, M. C. (2006). Caracterización fenotípica y funcional de los linfocitos B infiltrantes en islotes pancreáticos en ratones NOD. Identificación del antígeno neuroendocriono reconocido predominantemente por esta población celular. (Thesis). Universitat Autònoma de Barcelona. Retrieved from http://hdl.handle.net/10803/3782

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Puertas Castro, Mª Carmen. “Caracterización fenotípica y funcional de los linfocitos B infiltrantes en islotes pancreáticos en ratones NOD. Identificación del antígeno neuroendocriono reconocido predominantemente por esta población celular.” 2006. Thesis, Universitat Autònoma de Barcelona. Accessed March 01, 2021. http://hdl.handle.net/10803/3782.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Puertas Castro, Mª Carmen. “Caracterización fenotípica y funcional de los linfocitos B infiltrantes en islotes pancreáticos en ratones NOD. Identificación del antígeno neuroendocriono reconocido predominantemente por esta población celular.” 2006. Web. 01 Mar 2021.

Vancouver:

Puertas Castro MC. Caracterización fenotípica y funcional de los linfocitos B infiltrantes en islotes pancreáticos en ratones NOD. Identificación del antígeno neuroendocriono reconocido predominantemente por esta población celular. [Internet] [Thesis]. Universitat Autònoma de Barcelona; 2006. [cited 2021 Mar 01]. Available from: http://hdl.handle.net/10803/3782.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Puertas Castro MC. Caracterización fenotípica y funcional de los linfocitos B infiltrantes en islotes pancreáticos en ratones NOD. Identificación del antígeno neuroendocriono reconocido predominantemente por esta población celular. [Thesis]. Universitat Autònoma de Barcelona; 2006. Available from: http://hdl.handle.net/10803/3782

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

12. Attaoua, Chaker. Etude des mécanismes moléculaires de résistance différentielle du mélanome malin aux vincalcaloïdes : Study of the molecular mechanisms of malignant melanoma differential resistance to vinca alkaloids.

Degree: Docteur es, Biologie Santé, 2013, Université Montpellier I

URL: http://www.theses.fr/2013MON13505

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Le mélanome malin (MM) est un cancer très réfractaire aux thérapies anticancéreuses, dont les vincalcaloïdes (VAs). Afin d'étudier le rôle de la GSTM1 (glutathion S-transférase… (more)

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Le mélanome malin (MM) est un cancer très réfractaire aux thérapies anticancéreuses, dont les vincalcaloïdes (VAs). Afin d'étudier le rôle de la GSTM1 (glutathion S-transférase 1) et la MRP1 (multidrug resistance protein 1) dans la résistance acquise du MM aux VAs, nous avons établi 4 modèles cellulaires de résistance à la vincristine (CAL1R-VCR), à la vindésine (CAL1R-VDS), à la vinorelbine (CAL1R-VRB) et à la vinflunine (CAL1R-VFL), par exposition continue de cellules du MM (CAL1-wt), pendant un an, à ces anticancéreux. L'expression d'ne GSTM1 fonctionnelle est spécifiquement observée (RT-PCR, western blot, activité GST totale) dans les cellules résistantes. Le curcumin (inhibiteur de GSTM1), la BSO (inhibiteur de synthèse de glutathion) et le MK571 (inhibiteur de MRP1), réduisent considérablement le résistance acquise à la VCR et à la VDS mais pas à la VRB ou à la VFL. Toutefois, tous ces VAs réduisent spécifiquement l'activité GSTM1. Ces données montrent l'implication différentielle de GSTM1 et MRP1 dans la résistance aux VAs. Pour déterminer les mécanismes moléculaires de cette chimiorésistance, nous avons réalisé une étude pangénomique (biopuces Affymetrix HG-U133 Plus 2.00) sur les lignées CAL1 (wt et R). Le regroupement hiérarchique (par Cluster et TreeView) des données des puces a révélé une similarité entre les profils d'expression génique de CAL1R-VRB et CAL1-wt mais aussi entre ceux de CAL1R-VCR et CAL1R-VDS. L'analyse bioinformatique (par IPA) des transcrits les plus différemment exprimés entre les lignées cellulaires, a mis en évidence 6 réseaux géniques connus pour leur rôle dans la chimiorésistance tumorale. Le programme FatiGO a révélé 3 termes biologiques sur-représentés (> 60%) dans CAL1R (ribosome, filaments intermédiaires du cytosquelette, récepteurs olfactifs) tandis que l'étude fonctionnelle (invalidation génique par siRNA, test de viabilité) de GPR143, KIT et SLC45A2 (gènes interagissant avec NF-κB et CCND1 (facteurs de la chimiorésistance tumorale), très exprimés dans CAL1-wt et muets dans CAL1R) a montré la faible tendance des deux premiers à être impliqués dans la résistance aux VAs.

Malignant melanoma (MM) is a very refractory tumor to anticancer therapies, including vinca alkaloïds (VAs). To investigate the role of GSTM1 (glutathione S-transferase μ1) and MRP1 (multidrug resistance protein 1) in MM acquired resistance to VAs, we established 4 cellular models of resistance to vincristine (CAL1R-VCR), to vindesine (CAL1R-VDS), to vinorelbine (CAL1R-VRB) and to vinflunine (CAL1R-VFL), by continuous exposure of MM cells (CAL1-wt), for one year, to these anticancer agents. The expression of a functional GSTM1 is specifically observed (RT-PCR, western blot, total GST activity) in resistant cells. Curcumin (GSTM1 inhibitor), BSO (glutathione synthesis inhibitor) and MK571 (MRP1 inhibitor), considerably reduce the acquired resistance to VCR and VDS but not that to VRB or VFL. However, all these VAs specifically reduce GSTM1 activity. These data show the differential involvement of GSTM1 and…

Advisors/Committee Members: Cuq, Pierre (thesis director).

Subjects/Keywords: Mélanome malin; Chimiorésistance; Vincalcaloïdes; Glutathion S-transférase Mu1; Multidrug resistance proteins 1; Transcriptome; Malignant melanoma; Chemoresistance; Vinca alkaloids; Glutathione S-transferase Mu1; Multidrug resistance proteins 1; Transcriptome; 616

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Attaoua, C. (2013). Etude des mécanismes moléculaires de résistance différentielle du mélanome malin aux vincalcaloïdes : Study of the molecular mechanisms of malignant melanoma differential resistance to vinca alkaloids. (Doctoral Dissertation). Université Montpellier I. Retrieved from http://www.theses.fr/2013MON13505

Chicago Manual of Style (16^th Edition):

Attaoua, Chaker. “Etude des mécanismes moléculaires de résistance différentielle du mélanome malin aux vincalcaloïdes : Study of the molecular mechanisms of malignant melanoma differential resistance to vinca alkaloids.” 2013. Doctoral Dissertation, Université Montpellier I. Accessed March 01, 2021. http://www.theses.fr/2013MON13505.

MLA Handbook (7^th Edition):

Attaoua, Chaker. “Etude des mécanismes moléculaires de résistance différentielle du mélanome malin aux vincalcaloïdes : Study of the molecular mechanisms of malignant melanoma differential resistance to vinca alkaloids.” 2013. Web. 01 Mar 2021.

Vancouver:

Attaoua C. Etude des mécanismes moléculaires de résistance différentielle du mélanome malin aux vincalcaloïdes : Study of the molecular mechanisms of malignant melanoma differential resistance to vinca alkaloids. [Internet] [Doctoral dissertation]. Université Montpellier I; 2013. [cited 2021 Mar 01]. Available from: http://www.theses.fr/2013MON13505.

Council of Science Editors:

Attaoua C. Etude des mécanismes moléculaires de résistance différentielle du mélanome malin aux vincalcaloïdes : Study of the molecular mechanisms of malignant melanoma differential resistance to vinca alkaloids. [Doctoral Dissertation]. Université Montpellier I; 2013. Available from: http://www.theses.fr/2013MON13505

13. Bardy, Guillaume. Effets insulino-sécrétoires et protecteurs de la quercétine au niveau de la cellule beta pancréatique : implication du calcium intracellulaire et de ERK1/2 : Effect of quercetin on insulin secretion and protection of pancreatic beta cell : implication of intracellular calcium and ERK1/2.

Degree: Docteur es, Biologie Santé, 2012, Université Montpellier I

URL: http://www.theses.fr/2012MON13515

►

Dans le diabète de type 2 établi, l'hyperglycémie chronique, un taux élevé d'acides gras libres et l'inflammation induisent un stress oxydatif (SO) au niveau de… (more)

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Dans le diabète de type 2 établi, l'hyperglycémie chronique, un taux élevé d'acides gras libres et l'inflammation induisent un stress oxydatif (SO) au niveau de la cellule beta. Le SO, qui apparaît dès le stade de pré-diabète, peut induire un dysfonctionnement précoce de cette cellule. Ainsi, la protection de la cellule β par des molécules anti-oxydantes pourrait ralentir la progression du pré-diabète au diabète.La quercétine, un flavonoïde, a présenté des propriétés antidiabétiques dans plusieurs études in vivo. Cependant, très peu de données traitent de son mécanisme d'action directement au niveau de la cellule beta. Dans ce contexte, nous avons étudié les effets de la quercétine au niveau de la cellule beta dans des conditions physiologiques et des conditions de SO.Nos résultats montrent qu'en présence de concentrations stimulantes de sécrétagogue, la quercétine potentialise la sécrétion d'insuline par un mécanisme impliquant l'augmentation de calcium intracellulaire et la potentialisation de ERK1/2 via l'activation des voies de la PKA et de la CaMK II. De plus, la quercétine protège la cellule beta du SO en sur-activant ERK1/2. Le resvératrol et la NAC, deux antioxydants de référence, sont inactifs dans ces conditions expérimentales.En absence de concentrations stimulantes de sécrétagogue, la quercétine induit une sécrétion d'insuline modérée en augmentant le calcium intracellulaire suite à une activation directe des CaV de type L. Dans ces conditions, l'activation de ERK1/2 induite par la quercétine, qui est indépendante de l'activation des voies de la PKA et de la CaMK II, ne serait pas impliquée dans le mécanisme sécrétoire. Nos résultats indiquent que le mécanisme d'action de la quercétine au niveau de la cellule β ne repose pas uniquement sur ses capacités anti-oxydantes mais fait intervenir des cibles pharmacologiques et la régulation de voies de signalisation intracellulaires.

In type 2 diabetes, chronic hyperglycaemia, elevated free fatty acids and inflammation induce oxidative stress (OS) in pancreatic β cell. SO, which appears at the stage of pre-diabetes, may induce early dysfunction of this cell. Thus, the β cell protection by antioxidant molecules could slow the progression of pre-diabetes to diabetes.Quercetin, a flavonoid, has shown antidiabetic properties in several in vivo studies. However, very few data address its mechanism of action directly at the β cell. In this context, we studied the effects of quercetin at the β cell under physiological conditions and conditions of OS.Our results show that in the presence of stimulating concentrations of secretagogue, quercetin potentiates insulin secretion by a mechanism involving increased intracellular calcium and potentiation of ERK1 / 2 via activation of the PKA and the CaMK II pathways. In addition, quercetin protects beta cell from OS via a suractivation of ERK1/2. Resveratrol and NAC, two antioxidants of reference are inactive under these experimental conditions.In the absence of stimulating concentration of secretagogue, quercetin induced…

Advisors/Committee Members: Oiry, Catherine (thesis director).

Subjects/Keywords: Quercétine; Sécrétion d'insuline; Canaux calciques voltage dépendant; Erk 1/2; Cellule beta pancréatique; Quercetin; Insulin secretion; Voltage dependent calcium channel; Erk 1/2; Pancreatic beta cell; 616

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Bardy, G. (2012). Effets insulino-sécrétoires et protecteurs de la quercétine au niveau de la cellule beta pancréatique : implication du calcium intracellulaire et de ERK1/2 : Effect of quercetin on insulin secretion and protection of pancreatic beta cell : implication of intracellular calcium and ERK1/2. (Doctoral Dissertation). Université Montpellier I. Retrieved from http://www.theses.fr/2012MON13515

Chicago Manual of Style (16^th Edition):

Bardy, Guillaume. “Effets insulino-sécrétoires et protecteurs de la quercétine au niveau de la cellule beta pancréatique : implication du calcium intracellulaire et de ERK1/2 : Effect of quercetin on insulin secretion and protection of pancreatic beta cell : implication of intracellular calcium and ERK1/2.” 2012. Doctoral Dissertation, Université Montpellier I. Accessed March 01, 2021. http://www.theses.fr/2012MON13515.

MLA Handbook (7^th Edition):

Bardy, Guillaume. “Effets insulino-sécrétoires et protecteurs de la quercétine au niveau de la cellule beta pancréatique : implication du calcium intracellulaire et de ERK1/2 : Effect of quercetin on insulin secretion and protection of pancreatic beta cell : implication of intracellular calcium and ERK1/2.” 2012. Web. 01 Mar 2021.

Vancouver:

Bardy G. Effets insulino-sécrétoires et protecteurs de la quercétine au niveau de la cellule beta pancréatique : implication du calcium intracellulaire et de ERK1/2 : Effect of quercetin on insulin secretion and protection of pancreatic beta cell : implication of intracellular calcium and ERK1/2. [Internet] [Doctoral dissertation]. Université Montpellier I; 2012. [cited 2021 Mar 01]. Available from: http://www.theses.fr/2012MON13515.

Council of Science Editors:

Bardy G. Effets insulino-sécrétoires et protecteurs de la quercétine au niveau de la cellule beta pancréatique : implication du calcium intracellulaire et de ERK1/2 : Effect of quercetin on insulin secretion and protection of pancreatic beta cell : implication of intracellular calcium and ERK1/2. [Doctoral Dissertation]. Université Montpellier I; 2012. Available from: http://www.theses.fr/2012MON13515

Universitat de Barcelona

14. Soriano Viladomiu, Alex. Factores inmunogenéticos relacionados con la resistencia/susceptibilidad a la infección por el VIH-1 y su progresión hacia SIDA.

Degree: Departament de Medicina, 2006, Universitat de Barcelona

URL: http://hdl.handle.net/10803/2198

► Los individuos expuestos al VIH-1 y no infectados y los pacientes infectados no progresores de larga duración son situaciones modelo para estudiar factores del huésped… (more)

▼ Los individuos expuestos al VIH-1 y no infectados y los pacientes infectados no progresores de larga duración son situaciones modelo para estudiar factores del huésped implicados en conferir resistencia a la infección / progresión y su conocimiento puede ser esencial para desarrollar nuevas estrategias preventivas y terapéuticas. El diseño del estudio fue un análisis de la frecuencia de nuevos factores inmunogenéticos, que potencialmente podrían estar implicados en la resistencia/pogresión de la infección, no descritos previamente en 4 grupos de individuos muy bien definidos: 1) pacientes VIH+ con progresión lenta de la infección, 2) pacientes con progresión normal de la infección, 3) individuos con exposición a la infección por el VIH, que permanecen seronegativos y 4) controles sanos. El primer factor inmunogenético analizado fueron los polimorfismos en el receptor alfa de la IL-4. La IL-4 in vitro disminuye la expresión de CCR5 y aumenta la expresión de CXCR4 y además potencia la diferenciación de los linfocitos Th hacia una respuesta tipo 2, por lo que las diferentes variantes podrían influir en la resistencia a la infección o progresión hacia sida. Los polimorfismos analizados fueron I50V en el exón 5 (extracelular) y 6 polimorfismos localizados en el exón 12 (intracelular). Los principales resultados obtenidos fueron: 1) la variante homozigota V50 se asoció con la progresión lenta de la infección por el VIH y 2) la presencia de haplotipos infrecuentes en el exón 12 se asoció a una mayor susceptibilidad a la infección por el VIH tras una exposición parenteral. El segundo trabajo parte de que la activación de linfocitos CD4 vía CD28 modula la expresión de los principales co-receptores del VIH-1, CCR5 y CXCR4. Por ello, se analizó la presencia de posibles posibles polimorfismos en la región 5'UTR del gen de CD28. Los resultados obtenidos fueron: 1) la presencia de un polimorfismo que consiste en la inserción de 5 nucleótidos y 2) que esta variante se encuentra con más frecuencia en los pacientes infectados con respecto a aquellos pacientes repetidamente expuestos al VIH por vía sexual, que permanecen seronegativos. Estos datos sugieren que esta variante favorecería la infección por el VIH a través de las mucosas. El tercer y último trabajo analiza el polimorfismo en la región no traducida del gen SDF-1 (SDF1-3'A), ligando natural del CXCR4. Esta mutación en su forma homozigota se ha relacionado con progresión lenta hacia el desarrollo de SIDA, aunque otros trabajos no confirman estos resultados e incluso lo contradicen. Las consecuencias biológicas de esta mutación no se conocían por lo que consideramos como objetivos de trabajo, correlacionar los niveles de SDF-1 con la presencia o no de la mutación SDF1-3'A, analizar el genotipo, los niveles de SDF-1 y la expresión de CXCR4 en los diferentes grupos de estudio. Las principales conclusiones fueron: 1) la mutación SDF1 3'A-3'A no se asoció a progresión lenta de la infección, 2) la presencia homozigota de la mutación SDF1-3'A, se asoció a… Advisors/Committee Members: Gatell Artigas, Josep Maria (director).

Subjects/Keywords: SIDA; Resistència a les malalties; VIH-1; Marcadorsimmunogenètics; Ciències de la Salut; 616

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Soriano Viladomiu, A. (2006). Factores inmunogenéticos relacionados con la resistencia/susceptibilidad a la infección por el VIH-1 y su progresión hacia SIDA. (Thesis). Universitat de Barcelona. Retrieved from http://hdl.handle.net/10803/2198

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Soriano Viladomiu, Alex. “Factores inmunogenéticos relacionados con la resistencia/susceptibilidad a la infección por el VIH-1 y su progresión hacia SIDA.” 2006. Thesis, Universitat de Barcelona. Accessed March 01, 2021. http://hdl.handle.net/10803/2198.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Soriano Viladomiu, Alex. “Factores inmunogenéticos relacionados con la resistencia/susceptibilidad a la infección por el VIH-1 y su progresión hacia SIDA.” 2006. Web. 01 Mar 2021.

Vancouver:

Soriano Viladomiu A. Factores inmunogenéticos relacionados con la resistencia/susceptibilidad a la infección por el VIH-1 y su progresión hacia SIDA. [Internet] [Thesis]. Universitat de Barcelona; 2006. [cited 2021 Mar 01]. Available from: http://hdl.handle.net/10803/2198.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Soriano Viladomiu A. Factores inmunogenéticos relacionados con la resistencia/susceptibilidad a la infección por el VIH-1 y su progresión hacia SIDA. [Thesis]. Universitat de Barcelona; 2006. Available from: http://hdl.handle.net/10803/2198

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Universitat de Barcelona

15. Navarrete Durán, Pilar. Estudio de los cambios virológicos y de inmunidad celular en tejido amigdalar tras tratamiento antiretroviral en pacientes infectados por HIV en estado temprano de la infección.

Degree: Departament de Medicina, 2007, Universitat de Barcelona

URL: http://hdl.handle.net/10803/2226

► Los reservorios del VIH-1 se establecen en fases muy iniciales de la infección. Un estudio reciente documenta la presencia de gran cantidad de ARN vírico… (more)

▼ Los reservorios del VIH-1 se establecen en fases muy iniciales de la infección. Un estudio reciente documenta la presencia de gran cantidad de ARN vírico en ganglios linfáticos de individuos expuestos dos días después de la aparición de síntomas asociados con la infección aguda, incluso antes de la detección de anticuerpos. También se ha demostrado la existencia de un pequeño pool de células de vida media larga, linfocitos T CD4+ infectados, a partir del cual se puede recuperar el virus mediante técnicas de cultivo ultrasensible, teniendo la mayoría de los linfocitos T CD4+ fenotipo memoria. La vida media de este reservorio es contradictoria, estimándose entre 6 y 43 meses aunque datos recientes sugieren que podría durar más de 60 meses. De todas maneras los linfocitos T CD4+ infectados que permanecen latentes son sólo uno de los reservorios en la infección por el VIH-1 existiendo otros como pueden ser el sistema nervioso central, el semen, el tejido renal y el tejido linfático que es el motivo principal de nuestros estudios. Los principales marcadores para el seguimiento y pronóstico de los pacientes infectados con el VIH-1 son la carga viral plasmática y las subpoblaciones de linfocitos T en sangre periférica. Su eficacia para el estudio de la replicación viral y la inmunodeficiencia o como predictores de la evolución de pacientes con o sin tratamiento ha sido ampliamente demostrada. Sin embargo, en ocasiones, pueden no ser suficiente para el estudio de los cambios acaecidos después de la terapia antirretroviral administrada ya que diversos trabajos han evidenciado discrepancias entre los hallazgos en sangre periférica y en tejido linfático, tanto al valorar la replicación viral como los cambios en los niveles de las subpoblaciones de linfocitos. Incluso se ha descrito la existencia de pacientes con carga viral plasmática indetectable pero con presencia de carga viral en varios compartimentos, entre ellos el tejido linfático. Esto podría explicar casos clínicos de respuesta discordante de pacientes con caída de linfocitos T CD4+ a pesar de tener un buen control de la replicación viral El manejo de la infección por el VIH-1 se basa actualmente en el uso de tratamientos antirretrovirales altamente efectivos combinados con la monitorización del efecto virológico del tratamiento en plasma. El objetivo de estos tratamientos es suprimir la replicación viral con tal de prevenir el desarrollo de resistencias y la progresión clínica, y permitir así la restauración de la función inmune. En diversos estudios de investigación se produce la discusión de cómo se produce la restauración inmunológica, de cual es la replicación viral residual después de la supresión de la viremia o porque existen discrepancias entre la carga viral y la respuesta de las células CD4+ en algunos pacientes infectados por el VIH-1 que reciben terapia antirretroviral. Este conocimiento de la dinámica de la replicación viral y de las poblaciones linfocitarias es esencial para poder combatir esta infección. Se cree que la CVTL influye sobre… Advisors/Committee Members: [email protected] (authoremail), true (authoremailshow), García Alcaide, Felipe (director), Alós i Hernández, Llúcia (director).

Subjects/Keywords: Limfòcits; Sistema limfàtic; VIH-1; Infeccions víriques; Anticossos; Ciències de la Salut; 616

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Navarrete Durán, P. (2007). Estudio de los cambios virológicos y de inmunidad celular en tejido amigdalar tras tratamiento antiretroviral en pacientes infectados por HIV en estado temprano de la infección. (Thesis). Universitat de Barcelona. Retrieved from http://hdl.handle.net/10803/2226

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Navarrete Durán, Pilar. “Estudio de los cambios virológicos y de inmunidad celular en tejido amigdalar tras tratamiento antiretroviral en pacientes infectados por HIV en estado temprano de la infección.” 2007. Thesis, Universitat de Barcelona. Accessed March 01, 2021. http://hdl.handle.net/10803/2226.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Navarrete Durán, Pilar. “Estudio de los cambios virológicos y de inmunidad celular en tejido amigdalar tras tratamiento antiretroviral en pacientes infectados por HIV en estado temprano de la infección.” 2007. Web. 01 Mar 2021.

Vancouver:

Navarrete Durán P. Estudio de los cambios virológicos y de inmunidad celular en tejido amigdalar tras tratamiento antiretroviral en pacientes infectados por HIV en estado temprano de la infección. [Internet] [Thesis]. Universitat de Barcelona; 2007. [cited 2021 Mar 01]. Available from: http://hdl.handle.net/10803/2226.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Navarrete Durán P. Estudio de los cambios virológicos y de inmunidad celular en tejido amigdalar tras tratamiento antiretroviral en pacientes infectados por HIV en estado temprano de la infección. [Thesis]. Universitat de Barcelona; 2007. Available from: http://hdl.handle.net/10803/2226

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Universitat de Barcelona

16. Sáinz Jaspeado, Miguel Guillermo. Regulación del aporte vascular en el Sarcoma de Ewing: Papel de la Caveolina-1.

Degree: 2012, Universitat de Barcelona

URL: http://hdl.handle.net/10803/107820

► We established low CAV1 expressing models by knocking down CAV1 in TC71, RDES and SKES1 Ewing sarcoma (ES) cells by stably transfecting a previously validated… (more)

▼ We established low CAV1 expressing models by knocking down CAV1 in TC71, RDES and SKES1 Ewing sarcoma (ES) cells by stably transfecting a previously validated shRNA construct. In vivo studies showed a decrease in tumor volume from the CAV1 knocked-down clones when compared with controls. This correlated with a reduction in microvascular density (MVD) and higher levels of necrosis. Conditioned media from CAV1 knocked-down cells showed reduced capability to promote migration of endothelial cells with no changes in proliferation. Different pro-angiogenic factors were analyzed by RT-PCR in the models and, downregulation of bFGF was observed in all four. Results suggested that CAV1 was indirectly affecting bFGF expression. EphA2 expression was observed in ES cell lines and tumor samples. CAV1 knocked-down cells showed a reduction in EphA2 phosphorylation as well as a displacement from the membrane to the cytoplasm. Furthermore, we showed that the CAV1/EphA2 interaction was necessary for Eph-mediated signaling. To further support these results, RDES and TC71 cells were stably transfected with a dominant negative of EphA2 that did not alter the expression of CAV1 (EphAh2-kd). EphA2-Kd models were able to replicate the effects observed in the CAV1 knocked-down models, where the stimulation of the TC71-EphA2-Kd model with the recombinant protein EfnA1, showed both the activation of AKT and the overexpression of bFGF. These results replicate the effect of silencing CAV1 and highlighted the importance of the kinase-dependent activity of EphA2 in the angiogenic process in ES. We decided to analyze the kinaseindependent role of EphA2 as a possible key in the process of vascular mimicry in ES. Our results showed that the silencing of CAV1 reduces the development of mimetic vessels in vivo and prevents the tubular formation in vitro. In addition, our results showed that the kinase-dependent activity of the receptor does not affect the process of vascular mimicry in ES. Moreover, we stably transfected a mutant that lacks all the cytoplasmic region of EphA2, blocking its kinase-dependent and –independent activities. Results showed a negative effect on the formation of tubular structures. These results confirm the importance of the pro-oncogenic activity of EphA2 in ES. Advisors/Committee Members: Universitat de Barcelona. Facultat de Medicina, [email protected] (authoremail), false (authoremailshow), Martínez Tirado, Òscar (director), true (authorsendemail).

Subjects/Keywords: Sarcoma d'Ewing; Sarcoma de Ewing; Ewing's sarcoma; Osteosarcoma; Biologia molecular; Biología molecular; Molecular biology; Caveolina-1; Angiogènesi; Neovascularización; Neovascularization; Ciències de la Salut; 616

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Sáinz Jaspeado, M. G. (2012). Regulación del aporte vascular en el Sarcoma de Ewing: Papel de la Caveolina-1. (Thesis). Universitat de Barcelona. Retrieved from http://hdl.handle.net/10803/107820

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Sáinz Jaspeado, Miguel Guillermo. “Regulación del aporte vascular en el Sarcoma de Ewing: Papel de la Caveolina-1.” 2012. Thesis, Universitat de Barcelona. Accessed March 01, 2021. http://hdl.handle.net/10803/107820.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Sáinz Jaspeado, Miguel Guillermo. “Regulación del aporte vascular en el Sarcoma de Ewing: Papel de la Caveolina-1.” 2012. Web. 01 Mar 2021.

Vancouver:

Sáinz Jaspeado MG. Regulación del aporte vascular en el Sarcoma de Ewing: Papel de la Caveolina-1. [Internet] [Thesis]. Universitat de Barcelona; 2012. [cited 2021 Mar 01]. Available from: http://hdl.handle.net/10803/107820.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Sáinz Jaspeado MG. Regulación del aporte vascular en el Sarcoma de Ewing: Papel de la Caveolina-1. [Thesis]. Universitat de Barcelona; 2012. Available from: http://hdl.handle.net/10803/107820

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Universitat Autònoma de Barcelona

17. Jiménez Moreno, Francesc Xavier. Importancia del fenotipo de la a1-antitripsina en las manifestaciones clínicas y en el pronóstico de las enfermedades sistémicas autoinmunes.

Degree: Departament de Medicina, 2001, Universitat Autònoma de Barcelona

URL: http://hdl.handle.net/10803/4403

► The a1-antitrypsin deficiency is a relatively frequent hereditary disease characterized by the reduction of plasma levels of a1-antitrypsin (a1-AT) and the presence of emphysema and… (more)

▼ The a1-antitrypsin deficiency is a relatively frequent hereditary disease characterized by the reduction of plasma levels of a1-antitrypsin (a1-AT) and the presence of emphysema and liver disease. a1-AT gene mutations motivate the inability to produce and secrete normal amounts of a1-AT. When a1-AT levels are less than 50 mg/dl, the available a1-AT is not sufficient to protect the pulmonar alveolus from the elastase causing a progressive lung destruction and emphysema, in smokers, in early ages (35-50 years). a1-AT deficency is accompained of lymphocyte disorders. Also, inflammatory response seems to be excessive in these patients because of a lesser inhibition of proteases. Some studies suggest a relationship between a1 deficient phenotypes and systemic autoimmune diseases, specially in rheumatoid arthritis and vasculitis. Within them, the association with PR3-ANCA positive vasculitis seems to be evident; the presence of a deficient phenotype seem to be associated with a more agressive clinical presentation. The main objectives of the thesis are: 1. To evaluate if, in our population, there exists a higher prevalence of sever (PiZZ) and moderate (PiMZ, SS and MS) deficient phenotypes of a1-AT in patients with systemic autoimmune diseases comparing to the general population. 2. To study if scleroderma, systemic lupus erythematosus (SLE), idiopathic inflammatory myopathies and vasculitis present a different clinical evolution and prognosis in patients with deficient phenotypes of a1-AT. 3. To analyse if there exists a higher incidence of lung, kidney and hepatic involvement in this group of diseases in patients with moderate or sever deficient phenotypes. 4. To study if the results are correlated with a1-AT levels. Patients with systemic autoimmune diseases were included in this study. 440 healthy volunteers constituted the control group (they were visited in a regular control at the Preventive Service of the Hospital). A prevalence study of a1-AT deficient phenotypes in several systemic autoimmune diseases and a case-control study were performed to analyse differences in clinical, analytical and prognostic variables depending on the phenotypes. For the analysis of this observational study, all deficient phenotypes were included in the same group (Pino MM) and compared with the normal phenotype (PiMM). A immunofelometry method with a ArrayTM Protein System autoanalyser was used to determine a1-AT plasma levels. Pi phenotypes were determined using the Weidinger technique. Studied variables were; epidemiological variables, clinical diagnosis, organ involvement, analytical parameters (phenotype, plasmatic a1-AT, biochemical. haematological and immunological values), administered treatments, number of relapses and mortality. The analysis of categorical variables was performed using a X2 test or a Fiher's test when necessary. Comparisons between means was performed using a Student T test or the non parametric U Mann-Whitney test. To estimate risks, a logistic regression was performed… Advisors/Committee Members: [email protected] (authoremail), true (authoremailshow), Vilardell, Miquel, 1946- (director).

Subjects/Keywords: Alfa-1-antitripsina; Esclerodermia; Vasculitis; Ciències de la Salut; 616

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APA (6^th Edition):

Jiménez Moreno, F. X. (2001). Importancia del fenotipo de la a1-antitripsina en las manifestaciones clínicas y en el pronóstico de las enfermedades sistémicas autoinmunes. (Thesis). Universitat Autònoma de Barcelona. Retrieved from http://hdl.handle.net/10803/4403

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Jiménez Moreno, Francesc Xavier. “Importancia del fenotipo de la a1-antitripsina en las manifestaciones clínicas y en el pronóstico de las enfermedades sistémicas autoinmunes.” 2001. Thesis, Universitat Autònoma de Barcelona. Accessed March 01, 2021. http://hdl.handle.net/10803/4403.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Jiménez Moreno, Francesc Xavier. “Importancia del fenotipo de la a1-antitripsina en las manifestaciones clínicas y en el pronóstico de las enfermedades sistémicas autoinmunes.” 2001. Web. 01 Mar 2021.

Vancouver:

Jiménez Moreno FX. Importancia del fenotipo de la a1-antitripsina en las manifestaciones clínicas y en el pronóstico de las enfermedades sistémicas autoinmunes. [Internet] [Thesis]. Universitat Autònoma de Barcelona; 2001. [cited 2021 Mar 01]. Available from: http://hdl.handle.net/10803/4403.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Jiménez Moreno FX. Importancia del fenotipo de la a1-antitripsina en las manifestaciones clínicas y en el pronóstico de las enfermedades sistémicas autoinmunes. [Thesis]. Universitat Autònoma de Barcelona; 2001. Available from: http://hdl.handle.net/10803/4403

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Universitat Autònoma de Barcelona

18. Flotats Giralt, Albert. Afección cardíaca en la infección por virus de la inmunodeficiencia humana tipo 1.

Degree: Departament de Medicina, 2008, Universitat Autònoma de Barcelona

URL: http://hdl.handle.net/10803/4518

► Cardiac involvement in HIV-1-infected patients includes pericardial effusion/pericarditis, dilated cardiomyopathy, myocarditis, tumour infiltration and pulmonary hypertension (PH). HIV-1 infection can affect the heart by different… (more)

▼ Cardiac involvement in HIV-1-infected patients includes pericardial effusion/pericarditis, dilated cardiomyopathy, myocarditis, tumour infiltration and pulmonary hypertension (PH). HIV-1 infection can affect the heart by different mechanisms such as immune alterations, opportunistic infections (HIV-1 itself and/or other microorganisms) and tumours, as well as drug toxicity (because of highly active antiretroviral therapy -HAART- and/or therapy of the opportunistic complications) and/or use of illicit drugs. The identification of cardiac involvement in HIV-1 infection may be difficult due to the frequent coexistence of pulmonary infections and other systemic complications, so that symptoms may erroneously be attributed to them. After the introduction of HAART, the incidence of cardiac involvement has decreased, but at the same time the risk of development of atherosclerosis and ischemic heart disease has increased. Studies about the incidence of cardiovascular disease and mortality in HIV-1-infected patients are limited by short periods of follow-up. Objectives: 1) To assess the prevalence of morphologic and functional cardiac involvement as well as of myocardial damage in HIV-1-infected patients by means of transthoracic echocardiography and (111)In-antimyosin scintigraphy, respectively. 2) To identify possible predictors of cardiac involvement. 3) To assess the incidence of hard cardiac events (heart failure, acute myocardial infarction -AMI- or cardiac death) and predictors of global mortality. Material and methods: Ninety-six consecutive patients at different stages of HIV-1 infection and from all groups at risk for the infection were included. None of the patients had known or suspected structural heart disease. All patients underwent echocardiography and cardiac (111)In-antimyosin scan. A subgroup of patients who presented altered results was reassessed six months later. Subsequently, a retrospective registration of hard cardiac events and global mortality was performed after a mean of follow-up of 7±3 years. Results: Twenty-five (26%) patients showed echocardiographic alterations, and 11 patients (11.5%) had abnormal (111)In-antimyosin scans. Most of the echocardiographic alterations corresponded to mild valvular heart disease, however, on account of the clinical relevance, it is important to point out that: two patients had left ventricle -LV- dilatation and mitral regurgitation (one of them with severe LV dilatation and mild tricuspid regurgitation added); one patient had basal septal akinesia suggestive of an old AMI and mild mitral regurgitation; one patient had mild LV hypertrophy and hypokinesia and paradox movement of the septum; and two patients had PH with right ventricle -RV- dilatation and tricuspid regurgitation (one of them with primary PH and global hypokinesia of the RV with moderate tricuspid regurgitation). No significant association between echocardiography and (111)In-antimyosin scintigraphy was found. The duration of the infection, although not significant, tended to be longer… Advisors/Committee Members: [email protected] (authoremail), true (authoremailshow), Domingo Pedrol, Pere (director), Carrió, Ignasi (director).

Subjects/Keywords: Ecocardiografía; Gammagrafía antimiosina; HIV-1; Ciències de la Salut; 616

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Flotats Giralt, A. (2008). Afección cardíaca en la infección por virus de la inmunodeficiencia humana tipo 1. (Thesis). Universitat Autònoma de Barcelona. Retrieved from http://hdl.handle.net/10803/4518

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Flotats Giralt, Albert. “Afección cardíaca en la infección por virus de la inmunodeficiencia humana tipo 1.” 2008. Thesis, Universitat Autònoma de Barcelona. Accessed March 01, 2021. http://hdl.handle.net/10803/4518.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Flotats Giralt, Albert. “Afección cardíaca en la infección por virus de la inmunodeficiencia humana tipo 1.” 2008. Web. 01 Mar 2021.

Vancouver:

Flotats Giralt A. Afección cardíaca en la infección por virus de la inmunodeficiencia humana tipo 1. [Internet] [Thesis]. Universitat Autònoma de Barcelona; 2008. [cited 2021 Mar 01]. Available from: http://hdl.handle.net/10803/4518.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Flotats Giralt A. Afección cardíaca en la infección por virus de la inmunodeficiencia humana tipo 1. [Thesis]. Universitat Autònoma de Barcelona; 2008. Available from: http://hdl.handle.net/10803/4518

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Freie Universität Berlin

19. Jäger, Philipp. vom zellulären Mechanismus bis zur systemweiten Protein-Analyse.

Degree: 2011, Freie Universität Berlin

URL: http://dx.doi.org/10.17169/refubium-8320

► Während meiner Doktorarbeit lag der Schwerpunkt meines wissenschaftlichen Interesses bei der Erforschung schädlicher Protein-Aggregate und von Entzündungsstoffen, und deren Rolle bei der Entstehung neurodegenerativer Erkrankungen.… (more)

▼ Während meiner Doktorarbeit lag der Schwerpunkt meines wissenschaftlichen Interesses bei der Erforschung schädlicher Protein-Aggregate und von Entzündungsstoffen, und deren Rolle bei der Entstehung neurodegenerativer Erkrankungen. Drei zentrale Fragen haben mich dabei beschäftigt: Spielt die Autophagie bei der Verstoffwechslung des Amyloid-Vorläufer Proteins (APP) im Gehirn eine Rolle? Hat die Aktivität der Autophagie einen Anteil an der Entstehung der Alzheimer Erkrankung? Und was für ein Zusammenhang besteht zwischen einer fortschreitenden, systemweiten Entzündungs-Reaktion, intrazellulärer Kommunikation und der Alzheimer Erkrankung im Menschen? Meine Doktoarbeit basiert auf der Entdeckung, dass Beclin 1 (BECN1), ein Protein, das eine wichtige Rolle bei der Initiation von Autophagie spielt, im Cortex von Alzheimer Patienten reduziert zu sein scheint. Unser Labor entwickelte daraufhin ein Alzheimer-Maus-Modell mit reduzierter BECN1 Expression und stellte fest, dass diese Mäuse unter erhöhter Ablagerung von Aβ Plaques, erhöhter Aktivität von Mikroglia und fortgeschrittenem Verlust von Nervenzellen leiden (Pickford et al., 2008). Um den Zusammenhang zwischen BECN1, Autophagie und Alzheimer Erkrankung besser zu verstehen, habe ich daraufhin eine Reihe verschiedener Zellkultur-Experimente entwickelt. Verringerung und Über-Exprimierung von BECN1 durch siRNA Plasmide und Lenti- Virus Partikel haben mir geholfen aufzuzeigen, dass der zelluläre APP Gehalt tatsächlich durch Autophagie reguliert werden kann. Dementsprechend kann APP gezielt abgebaut und eine Aβ-Ansammlung verringert werden, wenn man Autophagie entweder durch Nährstoffs-Entzug oder durch Pharmaka künstlich aktiviert (Jaeger et al., 2010). Um der Frage nachzugehen, wie Entzündungsstoffe, Immunsignale und zelluläre Kommunikations-Faktoren während einer neurodegenerativen Erkrankung die Vorgänge (u.U. auch die Autophagie) in Nervenzellen beeinflussen, hat unser Labor einen speziellen antikörper- basierten Biochip entwickelt. Mit diesem Biochip sind wir in der Lage, hunderte verschiedener Kommunikations-Faktoren (z.B. Chemokine, Zytokine, Wachstumsfaktoren, Neurotrophine usw.) in Blut-Plasma-Proben demenz-erkrankter Patienten oder gesunder Probanden zu messen. Basierend auf diesem Chip-Design habe ich neuartige Methoden zur Daten-Extraktion, Daten-Analyse und Daten- Interpretation entwickelt. Dabei habe ich eine signifikante Deregulation in verschiedenen Signal-Kaskaden entdeckt, wie zum Beispiel in der TNF-α oder der TGF-β Kaskade (Manuskript in Vorbereitung). Unser Labor ist nun damit beschäftigt, diese potenziellen Signal-Kaskaden weiter zu erforschen, und zu überprüfen, welche bei der beobachteten Reduktion der Autophagie beteiligt sein könnten. Advisors/Committee Members: m (gender), Prof. Dr. Tony Wyss-Coray (firstReferee), Prof. Dr. Gerd Multhaup (furtherReferee).

Subjects/Keywords: Autophagy; Alzheimer; Beclin 1; APP; Proteomics; 500 Naturwissenschaften und Mathematik::570 Biowissenschaften; Biologie::572 Biochemie; 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::616 Krankheiten

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Jäger, P. (2011). vom zellulären Mechanismus bis zur systemweiten Protein-Analyse. (Thesis). Freie Universität Berlin. Retrieved from http://dx.doi.org/10.17169/refubium-8320

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Jäger, Philipp. “vom zellulären Mechanismus bis zur systemweiten Protein-Analyse.” 2011. Thesis, Freie Universität Berlin. Accessed March 01, 2021. http://dx.doi.org/10.17169/refubium-8320.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Jäger, Philipp. “vom zellulären Mechanismus bis zur systemweiten Protein-Analyse.” 2011. Web. 01 Mar 2021.

Vancouver:

Jäger P. vom zellulären Mechanismus bis zur systemweiten Protein-Analyse. [Internet] [Thesis]. Freie Universität Berlin; 2011. [cited 2021 Mar 01]. Available from: http://dx.doi.org/10.17169/refubium-8320.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Jäger P. vom zellulären Mechanismus bis zur systemweiten Protein-Analyse. [Thesis]. Freie Universität Berlin; 2011. Available from: http://dx.doi.org/10.17169/refubium-8320

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Universitat de Barcelona

20. Garcia Recio, Susana. Cooperación oncogénica entre la citoquina pro-inflamatoria SP y el receptor tirosina quinasa ErbB-2/HER2.

Degree: 2012, Universitat de Barcelona

URL: http://hdl.handle.net/10803/126031

► INTRODUCTION: Inflammation is a hallmark of cancer. Chronic inflammation is tightly related to tumor development and progression and supplies the tumor with a milieu of… (more)

▼ INTRODUCTION: Inflammation is a hallmark of cancer. Chronic inflammation is tightly related to tumor development and progression and supplies the tumor with a milieu of proinflammatory cytokines that can modulate the inflammation-related tumor cell signaling. The vast majority of proinflammatory cytokines induce signal transduction through different families of heterologous G-protein–coupled receptors (GPCRs). Moreover, ERBB receptors transmodulation by GPCRs generates functional diversity in signal transduction. Tachykinins are neuropeptides and proinflammatory cytokines that promote cell survival and cancer progression by activating several GPCRs. In this work, we found that the pain-associated tachykinin Substance P (SP) through NK-1R signaling contributes to persistent transmodulation of the ERBB receptors, EGFR and HER2, in breast cancer (BC), acting to enhance malignancy and therapeutic resistance.OBJECTIVE: Given the relevance of SP signaling on RTKs basal activation, we aim to investigate if the pain-associated tachykinin SP contributes to persistent transmodulation of the ERBB receptors, EGFR and HER2, in BC, acting to enhance malignancy and therapeutic resistance. RESULTS: SP and its high-affinity receptor NK-1R were highly expressed in HER2+ primary breast tumors (relative to the luminal and triple-negative subtypes) and were overall correlated with poor prognosis factors. In BC cell lines and primary cultures derived from BC samples, we found that SP could activate HER2. Conversely, RNA interference-mediated attenuation of NK-1R, or its chemical inhibition, or suppression of overall GPCR-mediated signaling, all strongly decreased steady-state expression of EGFR and HER2. Moreover, the treatment with NK-1R antagonist L-733,060, reduced tumour growth only in SCID mice harboring HER2+ or EGFR+ tumour cells. Finally, we found that a chronic exposure to SP in vitro for over 5 months significantly increased BC cell resistance to anti-ERBB therapies, and the combination of the NK-1R antagonist L-733,060 with anti-HER2 therapies synergistically inhibits the proliferation of BC cells increasing their therapeutic effect.CONCLUSION: In this work, we identified a new aberrant signaling network in BC founded by the oncogenic co-operation between the tachykinergic system and HER2/EGFR signaling, and we demonstrated that it could be exploited for the development of new therapeutic strategies based on the dual inhibition of activation and transactivation mechanisms. Advisors/Committee Members: Universitat de Barcelona. Facultat de Medicina, [email protected] (authoremail), false (authoremailshow), Almendro Navarro, Vanessa (director), Gascón, Pere (director), true (authorsendemail).

Subjects/Keywords: Tumores de los tejidos blandos; Tumors de parts toves; Soft tissue tumors; Citoquines; Citoquinas; Cytokines; Sustancia P (SP); Substància P (SP); Substance P (SP); Neuroquímica; Neurochemistry; Receptor NK-1; NK-1 receiver; ERBB-2; Ciències de la Salut; 616

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Garcia Recio, S. (2012). Cooperación oncogénica entre la citoquina pro-inflamatoria SP y el receptor tirosina quinasa ErbB-2/HER2. (Thesis). Universitat de Barcelona. Retrieved from http://hdl.handle.net/10803/126031

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Garcia Recio, Susana. “Cooperación oncogénica entre la citoquina pro-inflamatoria SP y el receptor tirosina quinasa ErbB-2/HER2.” 2012. Thesis, Universitat de Barcelona. Accessed March 01, 2021. http://hdl.handle.net/10803/126031.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Garcia Recio, Susana. “Cooperación oncogénica entre la citoquina pro-inflamatoria SP y el receptor tirosina quinasa ErbB-2/HER2.” 2012. Web. 01 Mar 2021.

Vancouver:

Garcia Recio S. Cooperación oncogénica entre la citoquina pro-inflamatoria SP y el receptor tirosina quinasa ErbB-2/HER2. [Internet] [Thesis]. Universitat de Barcelona; 2012. [cited 2021 Mar 01]. Available from: http://hdl.handle.net/10803/126031.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Garcia Recio S. Cooperación oncogénica entre la citoquina pro-inflamatoria SP y el receptor tirosina quinasa ErbB-2/HER2. [Thesis]. Universitat de Barcelona; 2012. Available from: http://hdl.handle.net/10803/126031

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

21. Martínez Bosch, Neus. Characterization of Galectin-1 in Pancreatic Cancer: A sweet target for a bitter disease.

Degree: Departament de Ciències Experimentals i de la Salut, 2011, Universitat Pompeu Fabra

URL: http://hdl.handle.net/10803/80662

► Avui en dia, el càncer de pàncrees representa un dels tumors amb més elevats índex de mortalitat, per la qual cosa la recerca dirigida a… (more)

Subjects/Keywords: Càncer de pàncrees; Galectina-1; tPA; Desmoplasia; Metaplasia acinar ductal; Ratolins Ela-1-myc; Glicosilació; Pancreatic cancer; Galectin-1; Acinar-ductal metaplasia; Ela-1-myc mice; Glycosylation; 616

…this direction, we have deeply evaluated the role of Galectin-1 (Gal-1) - a protein… …crosstalk in vitro. We have also focused on the biochemical identification of tPA/Gal-1… …interaction domains. Furthermore, we have studied Gal-1 role in pancreatic tumor progression in vivo… …Gal-1 participates in proliferation, angiogenesis, stroma formation and necrosis in Ela-1… …effects result in an overall significant increase in the survival of Ela-1-myc mice with reduced…

10 more images…

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APA (6^th Edition):

Martínez Bosch, N. (2011). Characterization of Galectin-1 in Pancreatic Cancer: A sweet target for a bitter disease. (Thesis). Universitat Pompeu Fabra. Retrieved from http://hdl.handle.net/10803/80662

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Martínez Bosch, Neus. “Characterization of Galectin-1 in Pancreatic Cancer: A sweet target for a bitter disease.” 2011. Thesis, Universitat Pompeu Fabra. Accessed March 01, 2021. http://hdl.handle.net/10803/80662.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Martínez Bosch, Neus. “Characterization of Galectin-1 in Pancreatic Cancer: A sweet target for a bitter disease.” 2011. Web. 01 Mar 2021.

Vancouver:

Martínez Bosch N. Characterization of Galectin-1 in Pancreatic Cancer: A sweet target for a bitter disease. [Internet] [Thesis]. Universitat Pompeu Fabra; 2011. [cited 2021 Mar 01]. Available from: http://hdl.handle.net/10803/80662.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Martínez Bosch N. Characterization of Galectin-1 in Pancreatic Cancer: A sweet target for a bitter disease. [Thesis]. Universitat Pompeu Fabra; 2011. Available from: http://hdl.handle.net/10803/80662

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Universitat de Barcelona

22. Abad Adán, Elena. Caracterización de la entrada de Ca2+ "capacitativa" en células trabeculares.

Degree: Departament de Ciències Fisiològiques I, 2009, Universitat de Barcelona

URL: http://hdl.handle.net/10803/1139

► <i>High concentrations of endothelin-1 (ET-1), one of the most potent vasoconstrictor peptide, has been found in the aqueous humor of glaucomatous eyes. It is said… (more)

Subjects/Keywords: Vasoconstrictors; Endoltelina-1; Pressió intraocular (PIO); Neuropatia; Nervi òptic; Glaucoma; Ciències de la Salut; 616

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Abad Adán, E. (2009). Caracterización de la entrada de Ca2+ "capacitativa" en células trabeculares. (Thesis). Universitat de Barcelona. Retrieved from http://hdl.handle.net/10803/1139

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Abad Adán, Elena. “Caracterización de la entrada de Ca2+ "capacitativa" en células trabeculares.” 2009. Thesis, Universitat de Barcelona. Accessed March 01, 2021. http://hdl.handle.net/10803/1139.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Abad Adán, Elena. “Caracterización de la entrada de Ca2+ "capacitativa" en células trabeculares.” 2009. Web. 01 Mar 2021.

Vancouver:

Abad Adán E. Caracterización de la entrada de Ca2+ "capacitativa" en células trabeculares. [Internet] [Thesis]. Universitat de Barcelona; 2009. [cited 2021 Mar 01]. Available from: http://hdl.handle.net/10803/1139.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Abad Adán E. Caracterización de la entrada de Ca2+ "capacitativa" en células trabeculares. [Thesis]. Universitat de Barcelona; 2009. Available from: http://hdl.handle.net/10803/1139

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

23. Saavedra Ávila, Noemí Alejandra. The role of cyclin D3 in pancreatic β-cell metabolic fitness and viability in a cell cycle-independent manner. Implications in autoimmune diabetes.

Degree: Departament de Medicina Experimental, 2013, Universitat de Lleida

URL: http://hdl.handle.net/10803/272629

► La diabetes tipo 1 (T1D) es una enfermedad autoinmune causada por la destrucción de las células β productoras de insulina en los islotes pancreáticos por… (more)

▼ La diabetes tipo 1 (T1D) es una enfermedad autoinmune causada por la destrucción de las células β productoras de insulina en los islotes pancreáticos por parte de los linfocitos. En esta tesis pretendemos dar a conocer dianas moleculares de las células β responsables de pérdida de la célula β causadas por el ataque linfocitico. Desarrollamos un estudio de microarreglos en el cual encontramos genes expresados diferencialmente en células endócrinas del islote como consecuencia de la infiltración insulítica mediante la comparación de un modelo de ratón autoinmune susceptible No Obeso Diabético (NOD) con una cepa congénica libre de linfocitos NOD/SCID. Interesantemente, descubrimos que, la ciclina D3 (CcnD3) experimentó una disminución como consecuencia de un asalto inflamatorio de forma dosis dependiente, mientras que la actividad de proliferación de las células β no fue alterada. Además, células NIT-1 que sobreexpresan CcnD3 fueron protegidas de apoptosis espontánea y apoptosis inducida por un entorno proinflamatorio proporcionado por la IL-1β. Para demostrar la relación causal entre la represión de la CcnD3 y la muerte de las células β in vivo, hemos estudiado la aparición de la diabetes espontánea en ratones NOD deficientes en CcnD3 (NODCcnD3KO). Los ratones NODCcnD3KO desarrollan una diabetes exacerbada en comparación con sus compañeros de camada de tipo salvaje (WT) (88% contra el 61% respectivamente) y este hecho debido únicamente a la deficiencia de CcnD3 de las células β y no a un aumento de diabetogenicidad del repertorio linfocítico de los ratones NODCcnD3KO. Sin embargo, la exacerbación de la diabetes requiere la complicidad de ambos, la deficiencia de CcnD3 e inflamación, ya que los ratones NOD/SCIDCcnD3KO, los cuales carecen de linfocitos, no desarrollan diabetes espontánea. CcnD3 tiene también un papel escencial en la fisiología de las células β del páncreas, ya que los islotes deficientes de CcnD3 no experimentan cambios apropiados en las concentraciones intracelulares de Ca2+ en respuesta a diferentes concentraciones de glucosa en el medio. Este deterioro en el acoplamiento de la concentración de glucosa en el medio extracelular y aumento de la concentración intracelular de Ca2 + no es debido al cambio del nivel de expresión del transportador de GLUT-2 entre islotes NODCcnD3 KO y NODWT. Por otro lado, hemos desarrollado ratones transgénicos que sobreexpresan la ciclina D3 en células β pancreáticas (NOD/RIPCcnD3). Estos ratones muestran protección contra la diabetes autoinmune y rescatan a ratones NOD CcnD3KO de desarrollar diabetes exacerbada. Advisors/Committee Members: false (authoremailshow), Mora Giral, Concepció (director), false (authorsendemail).

Subjects/Keywords: Diabetis; CcnD3; Diabetis tipus 1 (DM1); Diabetis autoimmune; Type 1 Diabetes (T1D); Autoimmune diabetes; Diabetes tipo 1 (T1D); Diabetes autoinmune; Cèl·lules β; β cells; Célula β; Immunologia; 616

…56 10.18 NIT-1 cell transfectants… …84 11.6 NIT-1 cells… …89 ix 11.6.1 NIT-1 cells overexpressing CcnD3 are protected from spontaneous and IL… …89 11.5.2 NIT-1 cells overexpressing CcnD3 are protected against NOD leucocyteinduced… …114 x xi ABSTRACT Type 1 Diabetes (T1D) is an autoimmune condition…

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Saavedra Ávila, N. A. (2013). The role of cyclin D3 in pancreatic β-cell metabolic fitness and viability in a cell cycle-independent manner. Implications in autoimmune diabetes. (Thesis). Universitat de Lleida. Retrieved from http://hdl.handle.net/10803/272629

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Saavedra Ávila, Noemí Alejandra. “The role of cyclin D3 in pancreatic β-cell metabolic fitness and viability in a cell cycle-independent manner. Implications in autoimmune diabetes.” 2013. Thesis, Universitat de Lleida. Accessed March 01, 2021. http://hdl.handle.net/10803/272629.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Saavedra Ávila, Noemí Alejandra. “The role of cyclin D3 in pancreatic β-cell metabolic fitness and viability in a cell cycle-independent manner. Implications in autoimmune diabetes.” 2013. Web. 01 Mar 2021.

Vancouver:

Saavedra Ávila NA. The role of cyclin D3 in pancreatic β-cell metabolic fitness and viability in a cell cycle-independent manner. Implications in autoimmune diabetes. [Internet] [Thesis]. Universitat de Lleida; 2013. [cited 2021 Mar 01]. Available from: http://hdl.handle.net/10803/272629.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Saavedra Ávila NA. The role of cyclin D3 in pancreatic β-cell metabolic fitness and viability in a cell cycle-independent manner. Implications in autoimmune diabetes. [Thesis]. Universitat de Lleida; 2013. Available from: http://hdl.handle.net/10803/272629

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Universitat de Barcelona

24. Garriga Badia, Montserrat. Influencia de la infección por el virus respiratorio sincitial en el desarrollo inmunológico en niños de 0 a 2 años de edad.

Degree: Departament d'Obstetrícia i Ginecologia, Pediatria i Radiologia i Medicina Física, 2004, Universitat de Barcelona

URL: http://hdl.handle.net/10803/2455

► The aim of this study was to establish the relationship between respiratory syncytial virus and the modifications in immunity that cause appearance of childhood asthma.… (more)

▼ The aim of this study was to establish the relationship between respiratory syncytial virus and the modifications in immunity that cause appearance of childhood asthma. Two study groups: 1- CHILDREN WITH BRONCHIOLITIS. (Group A) The problem group of children was initially made up of 65 who were hospitalized at this center for their first episode of VRS positive bronchiolitis, from December 1997 to February 1998. 50 children completed the follow-up for 2 years. 2. HEALTHY CHILDREN (Group B) The second group, made up of 80 children. Thus only a specific determination was done and no follow-up was done with these infants. IL- 4 and IFN-gamma, adhesion molecules were measured (s VCAM-1, sL selectin). The clinical concept of Childhood Asthma: is defined as the appearance of 3 or more episodes of bronchial obstruction before 2 years of age and/or a history of: bronchial hyperactivity, outside of periods of respiratory re-infection. CONCLUSIONS 1.- Children with VRS bronchiolitis developed asthma 2 years after the onset of bronchiolitis at a rate of 44% (22 children). 2.- Factors conditioning the development into asthma in this group have been: history of a sibling with an allergic illness or a parent who is a smoker. 3.- The immunitory response to acute VRS infection was analomous in those that developed into asthma, with an increase of humoral (LB, Ig G, Ig A, Ig M the latter with p= 0,014) and decrease in cellular response (LT, LT4, LT8). 4.- Increased humoral immunitory and decreased cellular response normalized at 12 months. 5.- The average IL-4 and IFN gamma values were detected at normal expected values for the age at the time of the bronchiolitis. At 6 months increase of IL-4 and decrease of IFN-gamma in children that later presented asthma. This increase of IL4 and decrease of IFN-gamma was maintained up to 18 months. 6.-The total Ig E of those presenting asthma did not increase up to 18 months of age 7.- The <i>cytokine eosinofile</i> protein was found to be high at 6 and 12 months in children who later presented asthma. 8.- At 18 months of age the children who have suffered bronchiolitis present a statistically significant increase (p< 0,001) in molecular sL-selectine adhesion, related to children who have not suffered it. Advisors/Committee Members: [email protected] (authoremail), true (authoremailshow), Martín Mateos, M. A. (María Anunciación) (director).

Subjects/Keywords: Interleucina 4; Bronquiolitis; Asma; Mol·lècules d´adhesió; Virus respiratori sincitial; Interferó gamma; VCAM-1; sl-selectina; Ciències de la Salut; 616; 616.2

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Garriga Badia, M. (2004). Influencia de la infección por el virus respiratorio sincitial en el desarrollo inmunológico en niños de 0 a 2 años de edad. (Thesis). Universitat de Barcelona. Retrieved from http://hdl.handle.net/10803/2455

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Garriga Badia, Montserrat. “Influencia de la infección por el virus respiratorio sincitial en el desarrollo inmunológico en niños de 0 a 2 años de edad.” 2004. Thesis, Universitat de Barcelona. Accessed March 01, 2021. http://hdl.handle.net/10803/2455.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Garriga Badia, Montserrat. “Influencia de la infección por el virus respiratorio sincitial en el desarrollo inmunológico en niños de 0 a 2 años de edad.” 2004. Web. 01 Mar 2021.

Vancouver:

Garriga Badia M. Influencia de la infección por el virus respiratorio sincitial en el desarrollo inmunológico en niños de 0 a 2 años de edad. [Internet] [Thesis]. Universitat de Barcelona; 2004. [cited 2021 Mar 01]. Available from: http://hdl.handle.net/10803/2455.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Garriga Badia M. Influencia de la infección por el virus respiratorio sincitial en el desarrollo inmunológico en niños de 0 a 2 años de edad. [Thesis]. Universitat de Barcelona; 2004. Available from: http://hdl.handle.net/10803/2455

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Universitat de Barcelona

25. Larrousse Morellón, Maria. Avances en el diagnóstico de la fibrosis hepática, manejo y tratamiento de la hepatitis crónica por el virus de la hepatitis C en pacientes infectados por el virus de la inmunodeficiencia humana.

Degree: Departament de Medicina, 2009, Universitat de Barcelona

URL: http://hdl.handle.net/10803/2330

► DE LA TESIS: En los países desarrollados, la introducción del tratamiento antirretroviral de gran actividad (TARGA) ha revolucionado la perspectiva del paciente infectado por el… (more)

▼ DE LA TESIS: En los países desarrollados, la introducción del tratamiento antirretroviral de gran actividad (TARGA) ha revolucionado la perspectiva del paciente infectado por el virus de la Inmunodeficiencia Humana tipo 1(VIH), produciendo un aumento espectacular de la supervivencia y una reducción muy importante de las infecciones oportunistas y neoplasias asociadas al síndrome de inmunodeficiencia adquirida (SIDA). En este contexto, la infección crónica por el virus de la hepatitis C (VHC) ha tomado gran relevancia clínica situándose como una de las primeras causas de ingreso hospitalario y muerte en los pacientes infectados por el VIH. La coinfección de estos virus no es un proceso aislado. De los 40 millones estimados de pacientes infectados por el VIH-1 en el mundo, aproximadamente un tercio presenta una infección crónica por el VHC lo que supone unos 12 millones de pacientes coinfectados a nivel mundial. Aproximadamente el 30% de la población seropositiva está coinfectada por el VHC. Esta elevada tasa de prevalencia de coinfección se debe en gran medida a que ambos virus comparten similares vías de transmisión. Si nos centramos exclusivamente en los pacientes que han adquirido la infección por el VIH por vía parenteral, principalmente en pacientes adictos a drogas endovenosas o pacientes hemofílicos, este número se eleva aproximadamente a un 90% de los pacientes (6). Estudios epidemiológicos han demostrado que el 65% de los pacientes con adicción a drogas por vía parenteral presentan anticuerpos para el VHC a los 12 meses tras el inicio del consumo. Este dato permite calcular el tiempo que un paciente lleva infectado por el VHC. En los últimos años se ha detectado que los pacientes coinfectados por ambos virus tienen peor pronóstico que los monoinfectados por VHC. La progresión de la enfermedad hepática se encuentra acelerada, los pacientes presentan una mayor progresión a cirrosis, mayor incidencia de hepatocarcinoma, y menor supervivencia desde la primera descompensación respecto a los pacientes con monoinfectados por el VHC. Por tanto, la consideración del tratamiento de la VHC es una prioridad en el manejo y tratamiento de los pacientes coinfectados por el VIH y VHC. La presente tesis recoge un total de cinco artículos en los que se ha difundido la investigación asociada con la misma. El primero ("Noninvasive Diagnosis of Hepatic Fibrosis in HIV/HCV-Coinfected Patients". JAIDS 2007; 46:304-311) analiza los marcadores no invasivos de fibrosis hepática en pacientes infectados por el VIH y VHC. El segundo ("Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for treatment of HIV/HCV co-infected patients". AIDS. 2004; 18(13):27-36.) contiene un estudio clínico que compara dos estrategias de tratamiento de la hepatopatía por VHC con Peginterferon alfa-2b con ribavirina comparada con interferon alfa-2b con ribavirina en pacientes coinfectados por el VIH y el VHC. El tercer artículo ("Predictive Value of Early Virologic Response in… Advisors/Committee Members: [email protected] (authoremail), true (authoremailshow), Mallolas Masferrer, Josep (director), Laguno Centeno, Montserrat (director).

Subjects/Keywords: Virus de l'Hepatitis C (VHC); Síndrome d'Immunodeficiència Adquirida (SIDA); Tractament antiretroviral de gran activitat (TARGA; Virus de l'Immunodeficiència Humana tipus 1 (VIH); Ciències de la Salut; 578; 616

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Larrousse Morellón, M. (2009). Avances en el diagnóstico de la fibrosis hepática, manejo y tratamiento de la hepatitis crónica por el virus de la hepatitis C en pacientes infectados por el virus de la inmunodeficiencia humana. (Thesis). Universitat de Barcelona. Retrieved from http://hdl.handle.net/10803/2330

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Larrousse Morellón, Maria. “Avances en el diagnóstico de la fibrosis hepática, manejo y tratamiento de la hepatitis crónica por el virus de la hepatitis C en pacientes infectados por el virus de la inmunodeficiencia humana.” 2009. Thesis, Universitat de Barcelona. Accessed March 01, 2021. http://hdl.handle.net/10803/2330.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Larrousse Morellón, Maria. “Avances en el diagnóstico de la fibrosis hepática, manejo y tratamiento de la hepatitis crónica por el virus de la hepatitis C en pacientes infectados por el virus de la inmunodeficiencia humana.” 2009. Web. 01 Mar 2021.

Vancouver:

Larrousse Morellón M. Avances en el diagnóstico de la fibrosis hepática, manejo y tratamiento de la hepatitis crónica por el virus de la hepatitis C en pacientes infectados por el virus de la inmunodeficiencia humana. [Internet] [Thesis]. Universitat de Barcelona; 2009. [cited 2021 Mar 01]. Available from: http://hdl.handle.net/10803/2330.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Larrousse Morellón M. Avances en el diagnóstico de la fibrosis hepática, manejo y tratamiento de la hepatitis crónica por el virus de la hepatitis C en pacientes infectados por el virus de la inmunodeficiencia humana. [Thesis]. Universitat de Barcelona; 2009. Available from: http://hdl.handle.net/10803/2330

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

26. Murillas Angoiti, Javier. Tratamiento e historia natural de la Hepatitis crónica C en pacientes coinfectados por VIH-1.

Degree: Departament de Medicina, 2009, Universitat de Barcelona

URL: http://hdl.handle.net/10803/2331

► En la segunda mitad del siglo XX se produjo probablemente la diseminación inicial del virus de la hepatitis C (VHC) a través de inyecciones parenterales… (more)

▼ En la segunda mitad del siglo XX se produjo probablemente la diseminación inicial del virus de la hepatitis C (VHC) a través de inyecciones parenterales poco seguras, procedimientos médicos y quirúrgicos invasivos, y transfusiones de sangre y hemoderivados. A finales de los años setenta se extendió en España el uso intravenoso de drogas, fundamentalmente heroína, lo que abrió una nueva vía de contagio: el uso compartido de material de inyección de drogas intravenosas. El pico de máxima incidencia de nuevos consumidores de heroína inyectada fue a comienzos de la década de los ochenta. En Europa se observan tres patrones de transmisión, el Norte de Europa, con baja prevalencia 0,1%-1% de la población general, la región centroeuropea, con una prevalencia media, y el sur de Europa (sur de Francia, España, Italia y Grecia) con prevalencias de 2,5-3-5%. Con el control de la transmisión nosocomial y transfusional, los genotipos más prevalentes pasaron a ser los relacionados con la adicción a drogas por vía parenteral, 1b, 3 y 4, en detrimento de los genotipos 1a y 2. Apareció entonces la pandemia del síndrome de inmunodeficicencia adquirida SIDA, cuyo agente causal, el VIH, fue rápidamente identificado. Hasta 1989 no se identifica el agente responsable de la hepatitis crónica noA noB, el Flavivirus VHC. Al compartir mecanismos de transmisión, ambas infecciones se entrecruzaron, dando lugar a un solapamiento de las dos epidemias que según algunas estimaciones podría afectar a 10-12 millones de personas. En nuestro país, la cifra de personas infectadas por el VIH-1 es aproximadamente 160.000, de las cuales globalmente, el 55%-65% están coinfectados por VHC, siendo esta cifra mayor entre aquellos que adquirieron la infección vía parenteral, hemofílicos y adictos a drogas, entre los que puede alcanzar el 80-90% de prevalencia, y más baja entre aquellos que adquirieron la infección por transmisión sexual, en los que la prevalencia es tan baja como 4-8%; estas diferencias se deben a que el VHC se transmite muy eficazmente vía parenteral, se estima que el 90% de los adictos de infectan en el primer año de adicción, y poco eficazmente por transmisión sexual. La transmisión vertical, aunque algo mayor en pacientes coinfectados, está alrededor del 10%. La coexistencia en el mismo enfermo de ambas infecciones tiene efectos deletéreos para ambas enfermedades. En la mayoría de los pacientes la respuesta inmunológica frente al VHC llega tarde o no es suficientemente vigorosa o completa, lo que permite una replicación viral sostenida que, a través de errores de trascripción en los continuos ciclos de replicación viral, dará lugar a una cuasi especie del VHC cada vez más adaptada al ambiente del huésped y, por tanto, con mayor capacidad para eludir su sistema inmunitario. La coinfección, además, se asocia con títulos mas elevados de ARN-VHC sobretodo en pacientes con CD4 bajos lo cual posiblemente refleja un déficit en el control de la replicación del VHC secundario a la inmunodeficiencia causada por el VIH-1. El… Advisors/Committee Members: [email protected] (authoremail), true (authoremailshow), Mallolas Masferrer, Josep (director).

Subjects/Keywords: Síndrome d'Immunodeficiència Adquirida (SIDA); Virus de l'Immunodeficiència Humana tipus 1 (VIH); Virus de l'Hepatitis C (VHC); Ciències de la Salut; 578; 616

…ÍNDICE PREFACIO �� . �� ….7 INTRODUCIÓN 1. EPIDEMIOLOGÍA… …PACIENTES INFECTADOS POR VIH-1 �� 36 OBJETIVOS �� . ��.38 RESUMEN DE LAS… …PUBLICACIONES �� ............................ �� 39 DISCUSIÓN 1. OPTIMIZACIÓN DEL TRATAMIENTO DE LA… …HEPATITIS CRÓNICA C 1. 1. ¿ES PREFERIBLE LA UTILIZACIÓN DE PEGIFN ALFA 2-A FRENTE A PEGIFN ALFA 2… …53 5 2. HISTORIA NATURAL DE LA ENFERMEDAD HEPÁTICA EN PACIENTES INFECTADOS POR VIH-1 2.1…

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Murillas Angoiti, J. (2009). Tratamiento e historia natural de la Hepatitis crónica C en pacientes coinfectados por VIH-1. (Thesis). Universitat de Barcelona. Retrieved from http://hdl.handle.net/10803/2331

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Murillas Angoiti, Javier. “Tratamiento e historia natural de la Hepatitis crónica C en pacientes coinfectados por VIH-1.” 2009. Thesis, Universitat de Barcelona. Accessed March 01, 2021. http://hdl.handle.net/10803/2331.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Murillas Angoiti, Javier. “Tratamiento e historia natural de la Hepatitis crónica C en pacientes coinfectados por VIH-1.” 2009. Web. 01 Mar 2021.

Vancouver:

Murillas Angoiti J. Tratamiento e historia natural de la Hepatitis crónica C en pacientes coinfectados por VIH-1. [Internet] [Thesis]. Universitat de Barcelona; 2009. [cited 2021 Mar 01]. Available from: http://hdl.handle.net/10803/2331.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Murillas Angoiti J. Tratamiento e historia natural de la Hepatitis crónica C en pacientes coinfectados por VIH-1. [Thesis]. Universitat de Barcelona; 2009. Available from: http://hdl.handle.net/10803/2331

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

27. Lagares Tena, Laura María. Caveolina-1 en la progresión metastásica del Sarcoma de Ewing.

Degree: 2013, Universitat de Barcelona

URL: http://hdl.handle.net/10803/145475

► Ewing’s sarcoma (ES) is the second most common bone tumor in childhood and occurs with a high incidence of metastatic disease. Such tumors have a… (more)

▼ Ewing’s sarcoma (ES) is the second most common bone tumor in childhood and occurs with a high incidence of metastatic disease. Such tumors have a characteristic gene translocation that gives rise to a fusion protein, most commonly EWS/FLI1. This fusion protein acts as an aberrant transcription factor regulating the expression of different target genes involved in the initiation, maintenance and progression of the tumor. Our group described caveolin 1 (CAV1) as one of these target genes, describing its role in the malignant phenotype, tumorigenicity and resistance to chemotherapy-induced apoptosis of ES cell lines. To investigate the specific role of CAV1 in the metastatic process of this sarcoma, we established a model of low expression of CAV1 in cell lines of ES. Then, we measured changes in their migratory capacity, invasiveness and metastatic potential. In vitro, we found a lower migratory capability of CAV1 knockdown cells and a reduction in MMP-9 expression and MMP-2 activity. The regulation of MMP-2 activity seems to be related to the possible regulation that CAV1 exerts on the function of MT1- MMP, an essential protein for the activation of MMP-2. On the other hand, we suggest that CAV1 promotes the expression of MMP-9, both transcriptionaly and post-transcriptionaly, through regulating ERK1/2 signaling pathway. In our model, activated ERK1/2 would translocate to the nucleus where it would activate the transcription factors responsible for MMP-9 promoter activation. At the cytoplasm, activated ERK1/2 would phosphorylate and activate RSK2, which, in turn, would promote rpS6 activation, leading to protein translation initiation. Our results indicate that CAV1 is regulating migratory capability of ES cells by two different mechanisms; 1) through ERK1/2 pathway activation, 2) by linking several proteins bearing SH2 domains trough phosphorylated Tyr14 of CAV1. ERK1/2 seems to regulate cell migration in both RSK1-dependent and independent manner. In addition, experimental metastasis assays in vivo showed that, CAV1 knockdown cells had a lower incidence of pulmonary metastasis, a fact that correlated with a decrease in the expression of SPARC, a major adhesion protein in metastatic processes. In summary, our results demonstrate the importance of CAV1 in the metastatic process on ES tumors. Advisors/Committee Members: Universitat de Barcelona. Facultat de Medicina, [email protected] (authoremail), false (authoremailshow), Martínez Tirado, Òscar (director), true (authorsendemail).

Subjects/Keywords: Sarcoma d'Ewing; Sarcoma de Ewing; Ewing's sarcoma; Oncologia pediàtrica; Oncología pediátrica; Tumors in children; Metàstasi; Metástasis; Metastasis; Migració cel·lular; Migración celular; Cell migration; Caveolina-1; Caveolin 1; Proteïnes quinases; Proteínas quinasas; Protein kinases; Ciències de la Salut; 616

…sido posible. Gracias a todos. Caveolina-1 en la progresión metastásica del Sarcoma de… …Ewing Índice 1. Introducción �� ….................................... 1 1.1… …9 1.1.6.1. EWS/FLI1: factor de transcripción aberrante �� ….12 1.2. Caveolina-1… …II: artículos publicados �� ... 141 Caveolina-1 en la progresión… …metastásica del Sarcoma de Ewing 1. INTRODUCCIÓN Caveolina-1 en la progresión metastásica del…

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APA (6^th Edition):

Lagares Tena, L. M. (2013). Caveolina-1 en la progresión metastásica del Sarcoma de Ewing. (Thesis). Universitat de Barcelona. Retrieved from http://hdl.handle.net/10803/145475

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Lagares Tena, Laura María. “Caveolina-1 en la progresión metastásica del Sarcoma de Ewing.” 2013. Thesis, Universitat de Barcelona. Accessed March 01, 2021. http://hdl.handle.net/10803/145475.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Lagares Tena, Laura María. “Caveolina-1 en la progresión metastásica del Sarcoma de Ewing.” 2013. Web. 01 Mar 2021.

Vancouver:

Lagares Tena LM. Caveolina-1 en la progresión metastásica del Sarcoma de Ewing. [Internet] [Thesis]. Universitat de Barcelona; 2013. [cited 2021 Mar 01]. Available from: http://hdl.handle.net/10803/145475.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Lagares Tena LM. Caveolina-1 en la progresión metastásica del Sarcoma de Ewing. [Thesis]. Universitat de Barcelona; 2013. Available from: http://hdl.handle.net/10803/145475

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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