WorldCat Identities

École doctorale du Médicament (....-2009 / Paris)

Overview
Works: 371 works in 685 publications in 1 language and 697 library holdings
Roles: Other, 996, Degree grantor
Publication Timeline
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Most widely held works by École doctorale du Médicament (....-2009 / Paris)
Associations d'altérations génétiques et liens de coopérations oncogénique dans les cancers broncho-pulmonaires non à petites cellules by Karine Pallier( Book )

2 editions published in 2011 in French and held by 3 WorldCat member libraries worldwide

L'incidence globale et la mortalité dues au cancer du poumon fait de cette pathologie un problème majeur de santé publique. Les cancers bronchiques non à petites cellules (CBNPC) réprésentent 80 % des cancers bronchiques. Malgré les progrès observés au cours de vingt dernièrs années, le prognostic des patients atteints d'un CBNPC reste, tout stade confondu, médiocre avec 15 % de survie à 5 ans. L'objectif de cette thèse était d'identifier de nouvelles altérations moléculaires dans les CBNPC dans le but de mieux comprendre la carcinogenèse bronchique et son processus métastatique. Un travail global de caractérisation des CBNPC réalisé par des études pangénomiques nous a permis de mettre en évidence des régions d'intérêt. Nous avons focalisé notre travail sur trois grandes régions d'altérations : les altérations des gènes du cycle cellulaire, les altérations de la région 3q27-29 contenant TP63 et les altérations de la région 7p21.1 contenant TWIST1. L'ensemble de ces travaux a apporté des éléments de compréhension à la carcinogenèse bronchique et son processus métastatique grâce à l'identification de nouveaux liens de coopérations oncogéniques. La mise en évidence de nouvelles altérations moléculaires dans CBNPC permet de caractériser des sous-groupes de patients et pourrait permettre d'établir à terme une thérapie adaptée au "portrait moléculaire" spécifique de leur tumeur
Contribution à l'analyse des fonctions de la protéine PEA-15 : caractérisation d'un inhibiteur par criblage moléculaire et rôle dans la motilité astrocytaire by François Renault-Mihara( Book )

2 editions published in 2005 in French and held by 3 WorldCat member libraries worldwide

PEA-15 (Phosphoprotein Enriched in Astrocytes-15 kDa) était connue pour inhiber l'apoptose et la prolifération. A l'aide de souris PEA-15 -/- et sauvages, nous démontrons que PEA-15 inhibe également la migration astrocytaire par un mécanisme qui dépend de la protéine kinase C delta et plus particulièrement du fragment catalytique de celle-ci. La faible expression de PEA-15 dans des cellules tumorales ayant migré à distance de glioblastomes maintenus en culture organotypiques suggère que cet effet inhibiteur de PEA-15 sur la migration peut également intervenir dans un cadre pathologique. Par ailleurs, la mise en oeuvre d'une nouvelle stratégie de criblage basée sur le transfert de fluorescence intracellulaire entre la protéine étiquetée par la GFP et des composés de synthèse couplés à un fluorophore a permis de découvrir un composé de synthèse, 6D6-1, qui interagit avec PEA-15 et inhibe l'interaction entre PEA-15 et la kinase ERK qui sous-tend l'effet anti-prolifératif de PEA-15
Sommeil, sérotonine et dépression : étude de leurs interactions fonctionnelles by Daniela Popa( Book )

2 editions published in 2005 in French and held by 3 WorldCat member libraries worldwide

Mécanisme d'action de la lipoxygènase-1 de soja : étude à l'aide de phénylhydrazones by Sophie Bombard( Book )

1 edition published in 1990 in French and held by 3 WorldCat member libraries worldwide

Contribution à l'étude de la résistance de Plasmodium falciparum à l'atovaquone-proguanil by Lise Musset( Book )

2 editions published in 2006 in French and held by 2 WorldCat member libraries worldwide

Depuis 2000, l'atovaquone-proguanil (AP) est utilisée dans le traitement des accès simples à Plasmodium falciparum. Au cours de ce doctorat, la sensibilité in vitro à l'atovaquone de 477 isolats africains a été évalué à 1,79 ± 1,3nM. L'association s'est avérée efficace pour le traitement de 459 patients. Les échecs observés montrent que les échecs précoces (0,9%) sont liés à une malabsorption des principes actifs alors que les échecs tardifs (<0,1%) sont liés, au moment de la rechute, à des parasites hautement résistants in vitro (CI50>8000nM) présentant une mutation au niveau du gène du cytochrome b (Y268S ou Y268C), sans amplification associée de ce gène. L'analyse du génome mitochondrial des parasites isolés avant et après l'échec confirme le faible taux de polymorphisme de ce génome et révèle des origines multiples et indépendantes des parasites mutants. L'émergence de parasites résistants à l'AP est fréquente mais le risque actuel de sa dispersion est négligeable
Préparation d'un facteur X* clivable par la thrombine : anti-hémophilique potentiel by Virginie Quintard( Book )

2 editions published in 2002 in French and held by 2 WorldCat member libraries worldwide

Phytochimie des plantes du Vietnam : benzophénones polyprénylées de Garcinia spp, Clusiaceae, et isoflavones de Maclura tricuspidata, Moraceae by Wafaa Hamed( Book )

2 editions published in 2004 in French and held by 2 WorldCat member libraries worldwide

Dans le but d'isoler de nouveaux agents anticancéreux, la composition de deux nouvelles Clusiaceae récoltées au Vietnam, Garcinia oblongifolia et Garcinia oliveri, a été étudiée. Cette recherche a permis d'isoler une série de nouveaux benzoylphloroglucinols polyisoprénylés appelés oblongifolines, ainsi que d'autres déjà décrits comme la guttiférone F qui s'est révélée active sur la tubuline. Les guttiférones B et F n'avaient encore jamais été isolées de plantes du genre Garcinia.Une troisième plante appartenant au genre Maclura, M. tricuspidata, Moraceae a révélé une activité cytotoxique significative sur cellules KB. Des espèces du même genre, précédemment étudiées, s'étaient montrées riches en composés de structure proche de type benzoylphloroglucinol. L'espèce M. tricuspidata a révélé une intéressante activité cytotoxique sur cellules KB. L'étude de cette espèce vietnamienne a permis d'isoler une série d'isoflavones dont deux nouvelles, les macluspidatines A et B. La cytotoxicité du 6,8-diprénylorobol a été évaluée sur cellules KB et s'est révélée positive, comme pour la wightéone, dont l'activité cytotoxique était déjà connue
Evaluation pharmacologique des thérapeutiques antirétrovirales by Odile Launay( Book )

2 editions published in 2007 in French and held by 2 WorldCat member libraries worldwide

More than 10 years after the onset of active antiretroviral treatments, the treatment of HIV infection remains a complex therapeutic problem that requires a continued research through careful pharmacological evaluation. In numerous national multicentric therapeutic trials we showed: 1) that a "3 classes" therapy was less effective than a traditional "2 classes" therapy among naive or zidovudine/didanosine pretreated patients; 2) the absence of interaction between cetirizine and nevirapine but no efficacy of cetirizine in preventing cutaneous reactions to nevirapine therapy; 3) that the combination of lamivudine, ritonavir and indinavir can be used as a maintenance therapy in some highly pre-treated HIV-infected patients with resistant virus populations. The results of a pilot study showed a very weak diffusion of lopinavir at the level of female genital tract whereas the concentrations of indinavir in the genital tract were at times higher than those measured in plasma suggesting an active transport at this site
Apport du suivi thérapeutique et de la pharmacocinétique / pharmacodynamique de population pour l'adaptation posologique des médicaments : application aux statines et au méthotrexate by Démiana William Faltaos( Book )

2 editions published in 2006 in French and held by 2 WorldCat member libraries worldwide

Notre travail consiste à appliquer la modélisation (PK/PD) pour l'adaptation posologique des statines et du méthotrexate (MTX). Dans la première étude un modèle d'effet indirect précurseur dépendant a été développé pour trois statines ; l'atorvastatine, la fluvastatine et la simvastatine, où la production du LDL est inhibée dans le compartiment précurseur et la clairance des LDL est stimulée d'une façon dose et molécule dépendante. En se basant sur le modèle final nous avons établi des courbes de simulation de l'évolution des niveaux de LDL avec les différentes doses des trois statines. La deuxième étude portait sur la PK du MTX chez les patients atteints d'hémopathie lymphoïde. 51 patients ayant reçu 136 cures ont été inclus. Le modèle final a été appliqué à une estimation bayésienne en utilisant différentes stratégies d'échantillonnages limités. Le temps d'échantillonnage [H24, H48] a abouti à une prédiction satisfaisante des paramètres et des concentrations PK
Conception, synthèse et évaluation biologique de nouveaux dérivés de l'acronycine à potentialité antitumorale by Nicolas Gaboriaud-Kolar( Book )

2 editions published in 2008 in French and held by 2 WorldCat member libraries worldwide

The aim of this work is the preparation of natural occuring alcaloïd acronycine new derivatives. Two series were developped. The first one led to the synthesis of the triazoloacronycine new compound in acronycine series and of some interesting intermediates. The second one led to the synthesis of new psorospermin naturally occuring furanoxanthone. analogs in the benzo[b]acronycine series. For this, a new method involving micro-organism has been developped. The cytotoxic activity of the prepared compounds was evaluated on murine leukemic L1210 and human carcinoma KB-3-1 cells in vitro. Triazoloacronycine compound is four time more active than the naturaly occuring alcaloid. The psorospermin-acronycine analogs have a nanomolar activity and their mechanism of action was deeply studied. Those compounds are DNA alkylating agents targetting the major groove
Conception, synthèse et évaluation biologique de nouveaux antitumoraux en séries benzo[b]acridone et benzo[b]acronycine by Quyên Do( Book )

2 editions published in 2006 in French and held by 2 WorldCat member libraries worldwide

The pyranoacridone alkaloid acronycine exhibits antitumor properties against a large panel of tumor models. Its clinical evaluation was hampered by its the moderate potency and extremely low water-solubility. Esters in the 1,2-dihydro-1,2-dihydroxybenzo[b]acronycine series proved much more promising, particularly diacetate S-23906-1 currently under clinical trials. Numerous new derivatives were prepared in the benzo[b]acronycine series either including good leaving groups (carbamate type), or presenting increased stability (cinnamic esters). Their cytotoxic activity was determined on L-1210 and KB-3-1 cells. The most active compounds were also tested in vivo against C-38 carcinoma in Mice. Their mechanism of action involves DNA alkylation. Simplified analogues were synthesized in the N-méthylacridone and N-méthylbenzo[b]acronycine series. The methoxy group at position 1 appears as an essential structural requirement to observe biological activity in these latter series
Synthèse d'agonistes des récepteurs métabotropiques du glutamate du groupe III : applications thérapeutiques by Pauline Sibille( Book )

2 editions published in 2005 in French and held by 2 WorldCat member libraries worldwide

Etudes structurales de nouvelles cibles thérapeutiques du CMVH révélées par les dérivés benzimidazolés ribonucléosides by Anthony Couvreux( Book )

2 editions published in 2009 in French and held by 2 WorldCat member libraries worldwide

The Human Cytomegalovirus is a virus affecting all populations regardless of their socio-professional environment. Harmless in healthy subjects, the damage caused by the virus in the host proved disastrous when it becomes immunocompromised. Thus, people with HIV, people who have undergone organ transplants or infants are particularly susceptible to HCMV. The first inhibitors formulated for the viral polymerase have been ineffective due to the observation of multiple resistance mutations. A new class of molecule, benzimidazoles ribonucleoside derivatives, for stages of maturation and encapsidation, has emerged for the terminase complex proteins, pUL89 and pUL56, and the phosphotransferase pUL97 and its accessory protein,pUL27. Through the use of nuclear magnetic resonance, UV / Visible spectroscopy and circular dichroism, and homology modelling, we collected structural information on target of derivatives ribobenzimidazoles. We have proposed hypotheses about the mode of action of these molecules. Moreover, the discovery of a domain capable of interacting with the viral double-stranded DNA of HCMV has been described
Approches d'immunothérapie anti-mélanome sur la base de l'inhibition du facteur de croissance IGF-1 modulant l'expression du CD9 by Séverine Trabado( Book )

2 editions published in 2007 in French and held by 2 WorldCat member libraries worldwide

We developed a strategy of immunological treatment based on inhibition of the insulin-like growth factor I (IGF-I) in melanoma cell line (B16-F0 from C57Bl/6 mice). Immunological molecules (CMH-I, B7.1) weren't modulated by targeting IGF-I. On the other hand, downregulation of the tetraspanin molecule named CD9, implicated in cellular interactions, was observed. Moreover, delayed outgrowth and increased survival were evaluated after inoculation of modified cells in syngeneic hosts. Vaccines were realised using these blocked modified cells. Cytotoxic antibodies were shown to be present in the sera of mice that were able to lyse parental cells in the presence of rabbit complement. Moreover, spleen cells from CD8 subpopulation harvested from hosts vaccinated were able to inhibit in vivo outgrowth and in vitro proliferation of parental B16-F0. Consequently promising results were reported using IGF-I inhibition strategy leading to stimulate anti-melanoma immune effectors
Synthèse d'indolo[2,3-b]quinoxalines trisubstituées, une nouvelle famille de ligands des structures G-quadruplexes des télomères by Aurélie Jaouen( Book )

2 editions published in 2008 in French and held by 2 WorldCat member libraries worldwide

Telomeres, situated at the end of the chromosomes of eucaryotes cells, and telomerase, inactive enzyme in the healthy cells, are new selective targets for the antitumoral chemotherapy. The single-stranded part of telomeres can fold into quadruplexe structure (G4); molecules capable of leading or of stabilizing G4 are inhibitors of the enzyme. The objective of this thesis was the conception, the synthesis and the biological evaluation of new selective ligands of the structures G4. The previous works of the laboratory let think that indolo[2,3-b]quinoxalines trisubstituted by basic aminoalkyle chains could possess such properties. These products were obtained by multi-stages convergent syntheses after the development of regioselective methods to reach the intermediaries variously substituted. This study allowed to refute results previously published. The biophysical tests bring to light the stabilization of G4 by four of the indoloquinoxalines
Etude structurale par résonance magnétique nucléaire de deux protéines du VIH-1 interagissant avec les acides nucléiques, Vpr et NCp7 by Sarah Bourbigot( Book )

2 editions published in 2005 in French and held by 2 WorldCat member libraries worldwide

HIV replication cycle requires viral protein interactions with viral RNA and DNA. We studied the interaction between Vpr, regulation protein and NCp7, nucleocapsid protein and short oligonucleotides and Primer Binding Site (PBS) respectively. The PBS structures as a stem loop and interacts with the NCp7 during reverse transcription. This interaction induces strand transfer. Our study proves the capacity f NCp7 to slide between its two binding sites on the PBS, thus opening its secondary structure, which is necessary to the strand transfer. Vpr interacts with viral DNA and facilitates its import in cell nucleus. Having determined a "leucine zipper" dimer structure of Vpr(52-96), we showed by NMR, fluorescence and surface plasmon resonance an interaction between Vpr(52-96) and nucleic acids. Finding out structural features necessary for the interaction between the NCp7 and Vpr and their nucleotidic targets could be used to design new antiviral agents
Conséquences pharmacotoxicologiques des variations d'activité et des polymorphismes génétiques des cytochromes P4503A et de la P-glycoprotéine en transplantation rénale by Dany Anglicheau( Book )

2 editions published in 2005 in French and held by 2 WorldCat member libraries worldwide

A better understanding of individual variations in metabolism and side effects of immunosuppressive drugs could improve their safety and efficacy. We showed that several genetic polymorphisms of the CYP3A4, CYP3A5 and ABCB1 genes are associated with the interindividual variations of the pharmacokinetic characteristics of tacrolimus and rapamycin but not cyclosporine. We showed that P-glycoprotein is involved in the protection of human renal tubular cells against the cyclosporine toxicity by supporting its cellular efflux. Rapamycin limits the cellular efflux of cyclosporin and increases its intracellular concentration, a mechanism that may explain the exacerbation of cyclosporine nephrotoxicity observed clinically in the presence of rapamycin. We described an antiproliferative effect of rapamycin on human renal tubular cells and explored its mechanism
Contribution à l'étude du transport intestinal des acides aminés et de la synthèse protéique tissulaire au cours de la cryptosporidiose expérimentale chez le raton non sevré by Aline Topouchian( Book )

2 editions published in 2004 in French and held by 2 WorldCat member libraries worldwide

Cryptosporidium parvum is a protozoan parasite of the ileum. Cryptosporidiosis is now recognized as a major cause of diarrhea in young children. Cryptosporidiosis and malnutrition mutually worsening, we studied the nutritional consequences of the infection in suckling rats. At the peak of the infection, the parasite is responsible for : hypophagia, significant reduction in the ex vivo flux of leucine and glutamate, at the level of the highly infected ileum and the moderetly infected duodenum, reduction in the mRNA expression encoding for the glutamate transporter EAAT3 and reduction of the gastrocnemius protein synthesis rate. After spontaneous elimination of the parasite, the nutrient intake, the flux of both amino acids and the protein synthesis rate are normalized. Our results show that C. parvum is responsible for nitrogen malabsorption along the small intestine with no compensatory adaptation even after the parasite elimination. In the brush border membrane, the parasite induces actin network reorganization, altering the intracellular trafic of the transporter and/or its targeting to the plasma membrane. A role of hypophagia and of the immune system might be possible in the alteration of the expression and the functionnality of the transporters
 
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Alternative Names
École doctorale Médicament (EDM) (Paris)

EDM (Paris)

Languages
French (37)