Thèses sur le sujet « Modèle de progression de la maladie »
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Boucquemont, Julie. « Modèles statistiques pour l'étude de la progression de la maladie rénale chronique ». Thesis, Bordeaux, 2014. http://www.theses.fr/2014BORD0411/document.
Texte intégralThe objective of this thesis was to illustrate the benefit of using advanced statistical methods to study associations between risk factors and chrouic kidney disease (CKD) progression. In a first time, we conducted a literature review of statistical methods used to investigate risk factors of CKD progression, identified important methodological issues, and discussed solutions. In our sec ond work, we focused on survival analyses and issues with interval-censoring, which occurs when the event of interest is the progression to a specifie CKD stage, and competing risk with death. A comparison between standard survival models and the illness-death mode! for interval-censored data allowed us to illustrate the impact of modeling on the estimates of both the effects of risk factors and the probabilities of events, using data from the NephroTest cohort. Other works fo cused on analysis of longitudinal data on renal function. We illustrated the interest of linear mixed mode! in this context and presented its extension to account for sub-populations with different trajectories of renal function. We identified five classes, including one with a strong decline and one with an improvement of renal function over time. Severa! perspectives on predictions bind the two types of analyses presented in this thesis
Couronné, Raphaël. « Modélisation de la progression de la maladie de Parkinson ». Electronic Thesis or Diss., Sorbonne université, 2021. http://www.theses.fr/2021SORUS363.
Texte intégralIn this work, we developed statistical methods to model disease progression from patient’s repeated measurements, with a focus on Parkinson’s Disease (PD). A key challenge lies in the inherent heterogeneity of PD across patients, to the extent that PD is now suspected to encompass multiple subtypes or motor phenotypes. To gain insights on disease progression, research studies propose to gather a broad range of marker measurements, at multiple timepoints for each patients. These data allow to investigate the disease’s patterns of progression via statistical modeling. In a first part, we modeled the progression of scalar markers of PD. We extended on a disease progression model, namely the longitudinal spatiotemporal model. We then proposed to address data missingness, and to model the joint progression of markers of different nature, such as clinical scores, and scalar measurements extracted on imaging modalities. With this method, we modeled early motor progression in PD, and, in a second work, the heterogeneity of idiopathic PD progression, with a focus on sleep symptoms. In a second, independent, part of the manuscript, we tackled the longitudinal modeling of medical images. For these higher dimensionality data, Deep Learning is often used, but mostly in cross sectional setups, ignoring the possible inner dynamics. We proposed to leverage Deep Learning as a dimensionality reduction tool to build a spatiotemporal coordinate system of disease progression. We first took advantage of this flexibility to handle multimodal data. Then we leveraged the self-supervision induced by assuming monotonicity over time, to offer higher flexibility in modeling temporal variability
Sauty, Benoît. « Multimodal modelling of Alzheimer's Disease progression ». Electronic Thesis or Diss., Sorbonne université, 2023. http://www.theses.fr/2023SORUS348.
Texte intégralAlzheimer's disease (AD) is a multi-facet pathology, that can be monitored through a variety of data types. This thesis aims to leverage multimodal longitudinal data, especially imaging scans and cognitive tests, to provide a statistical description of the progression of AD and to enable individual forecasting of future decline. Mixed-effect disease progression models (DPMs) are commonly used for these tasks. In this context, our first contribution questions the frequent assumption that biomarkers follow linear or logistic functions over time, and we propose a geometric framework that assumes the data lie on a manifold and follow geodesics over time. We learn the Riemannian metric of the observation space and are able to model a wider variety of biomarkers, without priors on the shape of the trajectory over time. Using variational auto-encoders, we then extend this framework to neuroimaging data (MRI or PET scans), in order to provide high-dimensional progression models that describe the patterns of structural and functional alterations of the brain over the course of AD. We then apply this family of DPMs to clinical studies data in order to investigate the heterogeneity of AD progression, due to APOE-e4 genotype and sex on patterns of brain alterations. Lastly, we use said DPMs with a set of imaging and fluid biomarkers to identify the specific combinations of input features that best forecast cognitive declines in patients at different stages of the disease. The thesis demonstrates that DPMs can effectively model the progression of AD using a great variety of multimodal longitudinal data and provide valuable insights into the disease's clinical manifestations and progression. These findings can inform clinical trial design and facilitate more accurate prognosis and individualized treatment strategies for patients with AD
Buatois, Simon. « Novel pharmacometric methods to improve clinical drug development in progressive diseases ». Thesis, Sorbonne Paris Cité, 2018. http://www.theses.fr/2018USPCC133.
Texte intégralIn the mid-1990, model-based approaches were mainly used as supporting tools for drug development. Restricted to the “rescue mode” in situations of drug development failure, the impact of model-based approaches was relatively limited. Nowadays, the merits of these approaches are widely recognised by stakeholders in healthcare and have a crucial role in drug development for progressive diseases. Despite their numerous advantages, model-based approaches present important drawbacks limiting their use in confirmatory trials. Traditional pharmacometric (PMX) analyses relies on model selection, and consequently ignores model structure uncertainty when generating statistical inference. The problem of model selection is potentially leading to over-optimistic confidence intervals and resulting in a type I error inflation. Two projects of this thesis aimed at investigating the value of innovative PMX approaches to address part of these shortcomings in a hypothetical dose-finding study for a progressive disorder. The model averaging approach coupled to a combined likelihood ratio test showed promising results and represents an additional step towards the use of PMX for primary analysis in dose-finding studies. In the learning phase, PMX is a key discipline with applications at every stage of drug development to gain insight into drug, mechanism and disease characteristics with the ultimate goal to aid efficient drug development. In this thesis, the merits of PMX analysis were evaluated, in the context of Parkinson’s disease. An item-response theory longitudinal model was successfully developed to precisely describe the disease progression of Parkinson’s disease patients while acknowledging the composite nature of a patient-reported outcome. To conclude, this thesis enhances the use of PMX to aid efficient drug development and/or regulatory decisions in drug development
Sautière, Pierre-Éric. « Mise au point d'un modèle cellulaire de dégénérescence neurofibrillaire de type alzheimer ». Lille 1, 1994. http://www.theses.fr/1994LIL10012.
Texte intégralPeyre, Matthieu. « Modélisation de la tumorigenèse méningée chez la souris : progression tumorale liée à Nf2 et Cdkn2ab et voies alternatives d'oncogenèse ». Paris 7, 2013. http://www.theses.fr/2013PA077109.
Texte intégralMeningioma is the most common primary nervous System tumor. Although most tumors are benign , they can recur even after total resection, present with significant morbidity and there is a growing proportion, up to 30%, of aggressive variants (WHO grade II and III). The creation of relevant genetically engineered mouse models is the cornerstone of future advances in meningioma treatment through pre-clinical testing and thorough dissection of molecular mechanisms of tumorigenesis. We here present the creation and characterization in vivo and in vitro of two new genetically engineered mouse models of meningioma : one model of Grade ll-lll meningioma through bi-allelic A//2 inactivation and homozygous Cdkn2ab deletion and one model of PDGF-(3-induced meningioma, with or without bi-allelic A//2 inactivation. On the basis of recent whole genome studies, we also set the bases of two future A//2-independant GEM meningioma models through Akt and Smo activation. The establishment of mouse meningioma cell lines and a syngenic orthotopic meningioma mouse model allowed the evaluation of a new handheld confocal imaging device and will eventually lead to future « co-trials »
Tabbekh, Mouna. « Rôle de CD5 dans la potentialisation de la réponse T cytotoxique et dans le contrôle de la progression tumorale dans un modèle in vivo ». Thesis, Paris 11, 2011. http://www.theses.fr/2011PA11T026.
Texte intégralA major challenge in tumor immunology is based on effective and prolonged induction of the effectorphase of antitumor immune response. A better understanding of the mechanisms involved in potentiatingthe antitumor activity of immune effectors, particularly the CTL infiltrating the tumor represents aconsiderable challenge in developing new approaches to immunotherapy. In this context we areparticularly interested in studying the role of CD5 in the control of tumor progression, particularly inpotentiating the cytotoxic activity of CTLs infiltrating B16 melanoma. Our results showed a significantdelay in tumor growth in CD5-/- mice as compared with wild type mice. The control of tumor growth inCD5-/- mice does not seem to correlate with a higher recruitment of T cells, but with increased cytotoxicityof infiltrating T cells against B16 cells. We have also shown that this response is transient and that thetumor escape from immune system takes place at a later stage of tumor progression. This tumor escapeappears to be associated with increased death by AICD of TIL CD8+ from CD5-/- mice as compared withTIL CD8+ from wild type mice wich correlated with the induction of FasL on the surface of TIL. In vivomodulation of Fas/FasL with an adenovirus AdFas-Fc protects tumor infiltrating T CD8+/CD5- fromapoptosis and thereby prevents the tumor escape. In addition, analysis of specific T lymphocyte repertoirein CD5-/- mice suggests that the control of tumor progression could be linked to a greater in situproliferation of specific CD5- T lymphocytes. Our results also show that immunization of CD5-/- miceusing different melanoma associated antigens contributes to the potentiation of antitumor immuneresponse. All these results highlight a particular interest in targeting of CD5 to improve currentapproaches to tumor immunotherapy
Pineau, sandra. « Etude de l'implication des microARNs dans la progression tumorale grâce au modèle réversible de la transformation leucocytaire induite par Theileria ». Paris 7, 2011. http://www.theses.fr/2011PA077133.
Texte intégralThe acquisition and maintenance of cellular identity involve an equilibrium between proliferation and differentiation. Imbalance between those two states can result in different types of diseases, including cancer. Tumor progression is a multistep process in which genetic and epigenetic modifications sequentially alter gene expression. To examine the impact of these mechanisms, we are studing a unique model of reversible bovine leukocyte transformation induced by an intracellular eukaryotic parasite: Theileria. Bovine leukocytes infected with Theileria exhibit a cancerous phenotype, but when the parasite is eliminated cells enter quiescence or apoptosis. We describe a three-partner positive feedback loop. We show that the microRNA-155 represses the expression of the protein DET1, a member of the COP1 complex which ubiquitinates c-Jun. We show that AP-1 activates thé expression of BIC which contains miR-155. This loop maintains the miR-155 and AP-1 action on their target genes and stimulates cell proliferation. Finally, we demonstrate that the deregulation of any loop member alters the expression of the two other members and leads to apoptosis. We have identified a new target of the microRNA let-7: Polycomb protein EZH2. EZH2 and let-7 expression were inversely correlated ; LIN28 expression, a let-7 post-transcriptional repressor, was correlated with EZH2 expression in models of cancer and cell differentiation. My results suggest a direct inhibition of EZH2 expression by let-7, correlates with of EZH2 target genes including ADRB2 protein involved in invasive processes. I also showed that let-7 overexpression in transformed cells decreased the invasive capacity
Delacôte, Claire. « Vers une meilleure compréhension de la maladie du foie liée à l'alcool et des facteurs influençant sa progression : approche de modélisation ». Thesis, Lille 2, 2020. http://www.theses.fr/2020LIL2S029.
Texte intégralIn France, excessive alcohol consumption is the leading cause of cirrhosis and hepatocellular carcinoma (HCC), ahead of viral hepatitis and metabolic syndrome. In 2016, there were nearly 10,500 deaths by cirrhosis or HCC, despite a significant decrease in per capita alcohol consumption since 1960 (26L in 1960, 11.7L in 2017).Alcohol drinkers are at risk of developing alcohol-related liver disease (ALD). It progresses from the initial stage of steatosis to more advanced stages of fibrosis and cirrhosis, which may lead to complications: decompensation and HCC. ALD is an asymptomatic disease prior to the onset of complications, and many patients are diagnosed late with life-threatening consequences.Implementing early actions targeting excessive alcohol drinkers could help to reduce liver morbidity and mortality through the avoidance or earlier diagnosis of complications. The evaluation of the possible benefit of such public health actions requires, on the one hand, knowledge of the different stages leading to the development of complications and, on the other hand, knowledge of the impact of risk factors on progression, in order to be able to determine the populations to target. Among the risk factors identified, the metabolic syndrome plays an important role. Thus, in order to understand the mechanisms of evolution of ALD, it is necessary to study in parallel those leading to non-alcoholic fatty liver disease (NAFLD).The natural history of ALD is still poorly described, especially for the stages preceding cirrhosis. Mathematical modeling provides a conceptual framework to overcome the ethical issues that would arise from a cohort study of the evolution of ALD.The main objective of this work is to mathematically reconstruct the natural history of ALD and to predict the associated morbidity and mortality. The secondary objectives are to estimate the incidence of this pathology and to identify the at-risk population. For this purpose, we developed a Markov model that simulates the trajectory of cohorts of individuals from the moment they start at-risk alcohol consumption until their death. It integrates the main risk factors described as associated with the progression of ALD in the literature (sex, age, overweight and obesity, amount of alcohol, genetic polymorphism). Unknown parameters of progression are estimated by a back-calculation method.Three steps were necessary to supply and calibrate this model : 1) characterize mortality by decompensated cirrhosis and HCC related to alcohol consumption or metabolic syndrome from data provided by the French National Hospital Discharge database; 2) set up a Markov model on hospitalization data of excessive consumers to estimate the progression of fibrosis; 3) implement a Markov model on survey data from the general French population to estimate the process of entry into at-risk alcohol consumption or the onset of overweight and obesity.In conclusion, this work is the first to characterize the progression of ALD in the general French population. It is based on robust epidemiological data to which new insights are provided. The developed tools could be used to test the impact of public health policies that could be implemented in populations most likely to develop liver damage
Kmetzsch, Virgilio. « Multimodal analysis of neuroimaging and transcriptomic data in genetic frontotemporal dementia ». Electronic Thesis or Diss., Sorbonne université, 2022. https://accesdistant.sorbonne-universite.fr/login?url=https://theses-intra.sorbonne-universite.fr/2022SORUS279.pdf.
Texte intégralFrontotemporal dementia (FTD) represents the second most common type of dementia in adults under the age of 65. Currently, there are no treatments that can cure this condition. In this context, it is essential that biomarkers capable of assessing disease progression are identified. This thesis has two objectives. First, to analyze the expression patterns of microRNAs taken from blood samples of patients, asymptomatic individuals who have certain genetic mutations causing FTD, and controls, to identify whether the expressions of some microRNAs correlate with mutation status and disease progression. Second, this work aims at proposing methods for integrating cross-sectional data from microRNAs and neuroimaging to estimate disease progression. We conducted three studies. Initially, we focused on plasma samples from C9orf72 expansion carriers. We identified four microRNAs whose expressions correlated with the clinical status of the participants. Next, we tested all microRNA signatures identified in the literature as potential biomarkers of FTD or amyotrophic lateral sclerosis (ALS), in two groups of individuals. Finally, in our third work, we proposed a new approach, using a supervised multimodal variational autoencoder, that estimates a disease progression score from cross-sectional microRNA expression and neuroimaging datasets with small sample sizes. The work conducted in this interdisciplinary thesis showed that it is possible to use non-invasive biomarkers, such as circulating microRNAs and magnetic resonance imaging, to assess the progression of rare neurodegenerative diseases such as FTD and ALS
Bône, Alexandre. « Learning adapted coordinate systems for the statistical analysis of anatomical shapes. Applications to Alzheimer's disease progression modeling ». Electronic Thesis or Diss., Sorbonne université, 2020. http://www.theses.fr/2020SORUS273.
Texte intégralThis thesis aims to build coordinate systems for shapes i.e. finite-dimensional metric spaces where shapes are represented by vectors. The goal of building such coordinate systems is to allow and facilitate the statistical analysis of shape data sets. The end-game motivation of our work is to predict and sub-type Alzheimer’s disease, based in part on knowledge extracted from banks of brain medical images. Even if these data banks are longitudinal, their variability remains mostly due to the large and normal inter-individual variability of the brain. The variability due to the progression of pathological alterations is of much smaller amplitude. The central objective of this thesis is to develop a coordinate system adapted for the statistical analysis of longitudinal shape data sets, able to disentangle these two sources of variability. As shown in the literature, the parallel transport operator can be leveraged to achieve this desired disentanglement, for instance by defining the notion of exp-parallel curves on a manifold. Using this tool on shape spaces comes however with theoretical and computational challenges, tackled in the first part of this thesis. Finally, if shape spaces are commonly equipped with a manifold-like structure in the field of computational anatomy, the underlying classes of diffeomorphisms are however most often largely built and parameterized without taking into account the data at hand. The last major objective of this thesis is to build deformation-based coordinate systems where the parameterization of deformations is adapted to the data set of interest
Assous, Maxime. « Modèle progressif de la maladie de parkinson après dysfonctionnement aigu des transporteurs du glutamate dans la substance noire chez le rat ». Thesis, Aix-Marseille, 2013. http://www.theses.fr/2013AIXM4034/document.
Texte intégralParkinson's disease (PD) is characterized by the progressive degeneration of substantia nigra (SN) dopaminergic neurons. Central players in PD pathogenesis, including mitochondrial dysfunction and oxidative stress, might affect the function of excitatory amino acid transporters (EAATs). Here, we investigated whether acute EAATs dysfunction might in turn contribute to the vicious cycles sustaining the progression of dopamine neuron degeneration. PDC application on nigral slices triggered sustained glutamate-mediated excitation selectively in dopamine neurons. In vivo time-course study (4-120 days) revealed that a single intranigral PDC injection triggers progressive degeneration of exclusively dopamine neurons with unilateral to bilateral and caudorostral evolution. This degenerative process associates GSH depletion and specific increase in γ-glutamyltranspeptidase activity, oxidative stress, excitotoxicity, autophagy and glial reaction. The anti-oxidant N-acetylcysteine and the NMDA receptor antagonists ifenprodil and memantine provided significant neuroprotection Transient compensatory changes in dopamine function markers in SN and striatum accompanied cell loss and axonal dystrophy. Motor abnormalities (hypolocomotion and forelimb akinesia) showed late onset, when ipsilateral neuronal loss exceeded 50%. These findings outline a functional link between EAATs dysfunction and several PD pathogenic mechanisms and pathological hallmarks, and provide the first acutely-triggered rodent model of progressive parkinsonism
ROGER, CHRISTOPHE. « Epidemiologie de l'anthracnose du pois proteagineux due a mycosphaerella pinodes etude analytique en vue de l'elaboration d'un modele mecaniste de progression de la maladie sur la plante ». Rennes, Agrocampus Ouest, 1999. http://www.theses.fr/1999NSARB107.
Texte intégralMounayar, Stéphanie. « Mécanismes de compensation dans un modèle de la maladie de Parkinson : approches multiples chez le singe exprimant une régression des symptômes moteurs après intoxication progressive au MTPT ». Paris 6, 2007. http://www.theses.fr/2007PA066480.
Texte intégralCattin, Marie-Elodie. « Etude des mécanismes physiopathologiques dans un modèle murin de dystrophie musculaire d'Emery-Dreifuss, la souris hétérozygote Lmna deltaK32/+ ». Phd thesis, Paris 6, 2012. http://www.theses.fr/2012PA066160.
Texte intégralLMNA gene encodes lamin A/C, ubiquitous proteins of the nuclear envelope. Some mutations of LMNA gene lead to Emery-Dreifuss muscular dystrophy (EDMD) that associates muscular disease and dilated cardiomyopathy (DCM) with conduction and/or rhythm defects. My work aimed at investigating the phenotype and the associated pathomechanisms in heterozygous LmnaΔK32/+ mice (Het), mutation associated with severe EDMD in patients. Het mice do not show any muscle defect. They progressively develop cardiac dysfunction and DCM, and die between 35 and 70 weeks of age. The evolution of DCM is associated with a modulation of cardiac lamin A/C protein level. Before the development of DCM, lamin A/C protein level is 50% lower in Het than Wt hearts, but do not differ between both groups thereafter. The reduced lamin A/C content resulted from K32-lamin degradation via the ubiquitin-proteasome system (UPS). The UPS function is altered in the heart of Het mice. Overexpression of K32-lamin in engineered heart tissue followed by inhibition of the proteasome results in nuclear aggregation of mutant lamin, suggesting a poison peptide effect of these proteins. To conclude, LmnaΔK32/+ mice are the first knock-in Lmna model with cardiac-specific phenotype at the heterozygous state. UPS plays a key role in mutant lamin degradation, limiting its negative impact upon heart tissue. Our data provide evidence for double pathophysiological mechanisms of DCM in LmnadelK32/+ mice: haploinsufficiency is associated with accumulation of a poison peptide
Cattin, Marie-Elodie. « Etude des mécanismes physiopathologiques dans un modèle murin de dystrophie musculaire d'Emery-Dreifuss, la souris hétérozygote Lmna deltaK32/+ ». Phd thesis, Université Pierre et Marie Curie - Paris VI, 2012. http://tel.archives-ouvertes.fr/tel-00828327.
Texte intégralRenard, Laurence. « Valorisation des bases médico-administratives de l'assurance maladie pour identifier et suivre la progression d'une pathologie, en étudier la prise en charge et estimer l'impact de l'implémentation d'une politique de santé grâce à leur utilisation dans un modèle médico-économique : Application au diabète de type 2 au Luxembourg ». Thesis, Paris 5, 2012. http://www.theses.fr/2012PA05S004/document.
Texte intégralType 2 diabetes (T2D) is a chronic disease associated with many severe and costly complications. In a context of budgetary constraint, it is necessary to obtain an estimate the amount of resources to allocate to the management of chronic diseases. This includes monitoring the epidemiologic and economic evolutions. A database was built from medico-administrative databases of the national health insurance of Luxembourg. It included the healthcare consumptions associated with diabetes and its complications, of all type 2 diabetic patients treated in Luxembourg between 2000 and 2006. The objectives were to study the fields of use of this database and the possible applications for public health decision-making. This thesis gives some examples. In 2006, T2D prevalence in Luxembourg was 3.79% (N= 17070). An algorithm was built and permitted to identify three stages of diabetic nephropathy (3.77% of T2D cases in 2006). The analysis of the adherence to European follow-up guidelines showed a critical situation associated to several factors (treating physician, type of treatment, living region…). The mean costs associated with patients in dialysis were estimated at 116 647€/patient in 2006. Finally, a health-economic evaluation showed the dominance of a strategy promoting peritoneal dialysis in Luxembourg over the present situation
Greillier, Laurent. « Développement de nouvelles stratégies visant à améliorer la prise en charge du mésothéliome pleural malin ». Thesis, Aix-Marseille, 2014. http://www.theses.fr/2014AIXM5068/document.
Texte intégralMalignant pleural mesothelioma (MPM) is a rare cancer with poor prognosis. As MPM diagnosis remains difficult today, we first assessed the potential value of transcriptome analysis, from cells in pleural fluid, with diagnostic purpose. If this approach looks feasible, its technical constraints make it incompatible with routine practice. The second axis of our work concerned MPM local treatment, with the assessment of intrapleural (IP) administration of two chemotherapy drugs: pemetrexed and lipoplatin. Results obtained in an animal model show that the pharmacokinetic profiles of these two drugs are significantly different between intravenous and IP administration. With the goal of identifying new therapeutic targets, we explored the adrenomedullin (AM) pathway in MPM. AM and its receptors are jointly expressed in pleural biopsies from MPM. Moreover we demonstrated in vitro that AM increases the proliferation, migration and invasion abilities of MPM cells, through the MAPK signaling pathway. Inhibition of AM or its receptors appears as a promising therapeutic strategy, because of its direct effects on malignant cells, but also its indirect effects, via tumor angiogenesis and lymphangiogenesis inhibition (in vivo). Finally, we assessed new endpoints for phase II clinical studies. We showed that the progression-free survival rate at 9 weeks is the most performant criterion to predict overall survival
Salomon, Remi. « La maladie de Hirschsprung : un modèle de maladie multigénique ». Paris 5, 2000. http://www.theses.fr/2000PA05N084.
Texte intégralKoval, Igor. « Learning Multimodal Digital Models of Disease Progression from Longitudinal Data : Methods & ; Algorithms for the Description, Prediction and Simulation of Alzheimer’s Disease Progression ». Thesis, Institut polytechnique de Paris, 2020. http://www.theses.fr/2020IPPAX008.
Texte intégralThis thesis focuses on the statistical learning of digital models of neurodegenerative disease progression, especially Alzheimer's disease. It aims at reconstructing the complex and heterogeneous dynamic of evolution of the structure, the functions and the cognitive abilities of the brain, at both an average and individual level. To do so, we consider a mixed-effects model that, based on longitudinal data, namely repeated observations per subjects that present multiple modalities, in parallel recombines the individual spatiotemporal trajectories into a group-average scenario of change, and, estimates the variability of this characteristic progression which characterizes the individual trajectories. This variability results from a temporal un-alignment (in term of pace of progression and age at disease onset) along with a spatial variability that takes the form of a modification in the sequence of events that appear during the course of the disease. The different parts of the thesis are ordered in a coherent sequence: from the medical problematic, followed by the statistical model introduced to tackle the aforementioned challenge and its application to the description of the course of Alzheimer's disease, and, finally, numerical tools developed to make the previous model available to the medical community
Meyer, Laurence. « Délétion CCR5-delta 32 et progression de la maladie VIH-1 ». Paris 11, 1999. http://www.theses.fr/1999PA11T021.
Texte intégralThe role of the Δ32 deletion on the gene coding for the CCR5 receptor for beta chemokines on HIV-1 disease progression was studied in HIV-infected patients followed in several prospective multicenter cohorts. Around 17% of patients with a known date of infection from the SEROCO cohort were heterozygous for the deletion : these patients progressed less rapidly since infection to AlDS or death than the other patients. Ln a collaborative study with the Amsterdam cohort study, this protective effect was observed independently of two other mutations on genes coding for the CCR2 receptor and the SDF-1 ligand. Early serum viral load was 0. 25 log lower in Δ32 heterozygous patients than in wild-type patients; this lower viral load explained partiy. The protective effect of the deletion in the Cox multivariate analysis. This study allowed us to describe an HIV-infected subject who was homozygous for the deletion, which confirms that homozygous patients are not totally protected from HIV infection. The relationship between the Δ32 deletion and the occurrence of several opportunistic infections was studied in 1657 patients followed in the SEROCO, HEMOCO and SEROGEST cohorts. The risk of toxoplasmosis as a first AIDS-defining illness since inclusion was significantly reduced in heterozygous patients, even after adjustment for age, CD4 cell count and primary specifie prophylaxis. Since most patients who are still followed in these cohorts are now treated by highly active antiretroviral therapy, we are going to study whether the deletion affects the response treatment. The relationship between pathophysiology of primary HIV-1 infection and the Δ32 deletion will be studied in the PRIMO cohort which has recruited since 1996 recently infected patients
Querin, Giorgia. « Unravelling the tangle of motor neuron diseases : insights from neuroimaging and neurophysiology Spinal cord multi-parametric magnetic resonance imaging for survival prediction in amyotrophic lateral sclerosis Multimodal spinal cord MRI offers accurate diagnostic classification in ALS The spinal and cerebral profile of adult spinal-muscular atrophy : a multimodal imaging study The motor unit number index (MUNIX) profile of patients with adult spinal muscular atrophy Presymptomatic longitudinal cord pathology in c9orf72 mutation carriers : longitudinal neuroimaging study ». Thesis, Sorbonne université, 2019. http://www.theses.fr/2019SORUS329.
Texte intégralMotor neuron diseases (MNDs) are characterized by dysfunction and loss of ventral horn MNs in the spinal grey matter (GM). Nevertheless, different MNDs such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA) present with specific clinical presentations. Magnetic resonance imaging (MRI) is the most powerful approach at the brain and spinal cord (SC) level to extract quantitative data on degeneration. At the same time, neurophysiological techniques including motor unit number index (MUNIX) could represent a useful tool to map MN loss. The objective of this project was to combine SC and brain MRI with MUNIX to better characterize degeneration in MNDs, with the aim of identifying possible markers of disease progression. In ALS patients, we showed that SC MRI parameters improve diagnostic and prognostic prediction. Secondly, we longitudinally analyzed a wide population of pre-symptomatic carriers of the c9orf72 mutation, detecting early and progressive cervical WM degeneration. Finally, we considered a cohort of SMN1-related adult SMA patients who underwent a SC and brain MRI protocol combined with MUNIX. We detected isolated cervical GM atrophy not associated with WM pathology. After 24 months observation time, significant MUNIX modifications were demonstrated, suggesting that neurophysiological techniques could be an effective biomarker of disease progression
Cadoche, Guy. « Mtpm : premier modèle animal expérimental de maladie de Parkinson : influence de l'âge et de l'étanol sur ce modèle ». Montpellier 1, 1989. http://www.theses.fr/1989MON11002.
Texte intégralMaksoud, Elie. « Régulations immunitaires dans un modèle Drosophile de la maladie d'Alzheimer ». Phd thesis, Université de Strasbourg, 2012. http://tel.archives-ouvertes.fr/tel-00911811.
Texte intégralMaksoud, Élie. « Régulations immunitaires dans un modèle Drosophile de la maladie d'Alzheimer ». Thesis, Strasbourg, 2012. http://www.theses.fr/2012STRAJ106/document.
Texte intégralAlzheimer’s disease (AD) is characterized by the accumulation of amyloid β (Aβ) in the brain. Several lines of evidences point towards a strong link between AD and neuroinflammation. However, the exact molecular events of the innate immune reactions against Aβ need to be elucidated. We used Drosophila as a model organism to study the impact of innate immune reactions on AD. During my PhD I have been able to: (1) establish a Drosophila model to study the inflammatory responses inAD, (2) demonstrate that the Drosophila inflammatory IMD pathway plays a neuroprotective role in the development of AD-like phenotypes, (3) generate the IMD interactome dataset that could help elucidate the mechanisms linking AD to neuroinflammation, and (4) introduce a forward genetic screen for the identification of modifier genes of AD. We believe that the outcomes from our Drosophila studies could provide the basis for new therapeutic interventions against AD
Moranne, Olivier. « Facteurs de risque de progression et de complications de la maladie rénale chronique ». Paris 11, 2008. http://www.theses.fr/2008PA11T023.
Texte intégralSaleh, Nadine. « Troubles hormonaux et leur implication dans la progression de la maladie de Huntington ». Thesis, Paris Est, 2009. http://www.theses.fr/2009PEST0061.
Texte intégralThe pathophysiological processes leading to neurodegeneration and the symptoms of Huntington's disease (HD) remain unidentified and current hypothesis do not explain the intra and interindividual heterogeneity of the evolution of these symptoms. Thus, the progression of the disease remains difficult or impossible to predict. In this context, it is important to explore other factors that appear to be involved in the pathogenic process of the disease but could also influence the evolution of these symptoms and predict disease progression. Several evidences reinforce the hypothesis of the existence of hormonal disorders in HD such as the atrophy of the hypothalamus and weight loss. Because of few studies, their quality and the discrepancies of their results, the existence of hormonal changes in Huntington's disease and particularly their relationship to disease progression remains controversial. The objective of this work is to describe the hormonal profile of the hypothalamicpituitary axis in HD in order to better understand the role of these hormones on the progression and on the pathophysiology of the disease. In our cross-sectional study, we identified an activation of the somatotropic axis (Growth Hormone / Insulin Growth Factor 1), an inhibition according to the severity of the disease in two axes: gonadotrope (Testosterone) and thyréotrope (Thyroid Stimulating hormone and triiodothyronine) but no change in hormones of corticotropic axis and prolactin. In addition, the somatotropic axis is overactive even in patients with early disease. To explain the link between these changes and the progression of the disease, a longitudinal study was done. The results of this study showed that only the elevated plasma IGF1 was predictive of cognitive impairment. All of our results provide a better description and understanding of the profile of the hypothalamic-pituitary axis in Huntington's disease. Pituitary axes are not all disturbed. The inverse relationship between activation of the somatotropic axis and cognitive impairment strengthens the hypothesis of a resistance to the effect of IGF1 in Huntington's disease like in Alzheimer's disease. In conclusion, given the involvement of IGF1 in the prediction of cognitive progression in Huntington's disease, it would be interesting to detect whether the biological changes of IGF1 are already present at the asymptomatic cognitive stage in order to use IGF1 as a biomarker of the onset or changes in cognitive symptoms. On the other hand, , it would be important to extend research on the mechanisms responsible for hormonal changes in Huntington's disease to better understand the link between these changes and symptoms of the disease
Troquier-Péricou, Laetitia. « Approche d'immunothérapie dans un modèle murin de pathologie Tau ». Thesis, Lille 2, 2011. http://www.theses.fr/2011LIL2S021/document.
Texte intégralTau pathology is a common lesion observed in more than twenty neurological disorders, refered to as Tauopathies. It corresponds to the aggregation of the microtubule associated protein Tau hyper and abnormally phosphorylated into neurofibrillary tangles. In Alzheimer's disease (AD), the most common age-related dementia, the distribution and progression of Tau pathology have been reported to be well-correlated to the cognitive decline. Currently, treatments remain essentially symptomatic. However, several therapeutic approaches, including immunotherapy, are being developed to treat Tau pathology. The work presented in this thesis aim to investigate the effects of both active and passive Tau immunotherapy in a transgenic mouse model of Alzheimer’s disease-like Tau pathology. THY-Tau22 mice overexpress a double-mutated isoform of the human Tau protein, whose expression is under the control of a neuronal promoter. Several lines of evidence suggest that this transgenic mouse model is reproducing early stages of AD. Indeed, at three month old, the THY-Tau22 mouse model presents a progressive impairment of learning and memory without major neuronal loss, in parallel to Tau accumulation in the hippocampus. Moreover, Tau is hyper and abnormally phosphorylated at different sites including Ser422. Noteworthy, the pSer422 epitope is a single abnormal site of phosphorylation present only in pathological conditions, rendering it of particular interest for immunotherapy. In this present thesis work, we showed that early vaccination against the phosphorylated Ser422 Tau protein reduced spatial memory impairment as measured by the Y-maze test. Interestingly, this is associated with the decrease of the abnormal phosphorylation of Tau in the hippocampus and with a significant reduction of insoluble Tau species. Based on these results, we generated a new monoclonal antibody raised against pSer422 (2H9) to evaluate the effects of passive immunotherapy. The antibody was injected every week, intraperitoneally (5mg/kg and 10mg/kg of 2H9 or saline buffer) in the THY-Tau22 mice. We show that this approach can prevent the appearance of spatial memory deficits as measured by the Y maze and the Morris water maze tests. Immunohistochemical analysis also revealed a reduction of abnormally phosphorylated Tau proteins in the hippocampus. To investigate the mechanisms underlying Tau immunotherapy, we performed stereotaxic injections of anti-phosphoTau antibodies in the hippocampus of THY-Tau22 mice. We showed that, once in the brain, anti-phosphoTau antibodies were located inside the neurons in contrast to the isotype control. Several recent studies of immunotherapy, suggest an involvement of macroautophagy in the antibody-mediated degradation. We showed that internalized antibodies colocalized with different markers of the lysosomal pathway (NPC1, Lamp2) confirming this hypothesis of a lysosomal-mediated degradation. However, since the blood-brain barrier is highly selective, the antibodies may more likely act in the periphery. Indeed, we showed that peripheral administration of 250μg of the 2H9 generates a significant increase of Tau proteins levels in plasma, suggesting a peripheral sink mechanism as for Aβ immunotherapy. Vaccination, which generates a polyclonal response, leads to a greater increase of plasmatic Tau that confirms the peripheral degradation of Tau. Overall, the results of this PhD work confirmed the promising potential of Tau immunotherapy for Alzheimer\\\\\\\'s disease and other Tauopathies treatment. Moreover, it address a new hypothesis suggesting that the antibodies mediated degradation of Tau proteins might be through a peripheral sink such as for Aβ
Brulin-Fardoux, Peggy. « Cadasil : contribution apportée par l'ultrastructure, l'immunohistochimie des vaisseaux et l'analyse du modèle animal ». Lille 2, 2003. http://www.theses.fr/2003LIL2MT25.
Texte intégralIn the field of vascular dementia which correspond to the second cause of dementia after Alzheimer disease in occidental countries, CADASIL is an autosomal dominant hereditary vascular dementia secondary to mutations of the gene Notch3. CADASIL is a systemic alteration of the vascular smooth muscle cells leading to an exclusive neurological disease. The neuroimagery is one main point in the diagnosis and discloses lesions in the deep white matter and in the deep gray matter. The main purpuse of this study us a better understanding of the CADASIL physiopathology. Three lines were developped : i) A morphological and morphometrical evaluation of the vessel wall alterations and their functional consequences, ii) a biochemical analysis of the specific deposits (GOMs) and iii) a study of a CADASIL murin model in order to observe the time course of the disease
Rousseau, Alix. « Modélisation de la progression tumorale dans un syndrome d'instabilité génétique, la maladie de Fanconi ». Sorbonne Paris Cité, 2015. http://www.theses.fr/2015USPCC243.
Texte intégralFanconi Anemia is a rare genetic disorder characterized by a progressive bone marrow failure phase, associated with a strong selective pressure that predisposes to clonal evolution and to the emergence of myelodysplastic syndromes (MDS) and also to acute leukemias myeloid (AML) with complex karyotypes in early adulthood. The study of this disease allows longitudinal analysis of early and late events of the myeloid oncogenesis in a context of genetic instability. In this work, we used combined approaches of genomic and functional analysis to understand the oncogenesis mechanisms in Fanconi anemia. CGH array analysis and sequencing of 50 samples from FA patients MDS/AML allowed us to describe the genetic abnormalities acquired in MDS1AML of FA patients. Interestingly, the results of genomic analysis showed an absence Of TP53 mutation in MDS of FA patients and in the progression to AML. These results have highlighted the possibility that the FA transformation process can go through alternative ways to inhibit the tumor suppressor P53 response. The genomic analysis also also allowed us to identify recurrent duplications of the long arm of chromosom 1 (1q -+) present at all stages of the bone marrow progression. It has been shown that these duplications systematically targeted HDMX gene. In addition, we have highlighted recurrent mutations of Runx I associated to the late stages of MDS/AML in FA patients. We set up in vitro and in vivo models that allowed us to demonstrate that the FA oncogenesis is a multi-stages process and requires the association of several genetic defects. The understanding of such mechanisms is crucial to understand the pathophysiology of Fanconi Anemia and may have repercussions beyond its borders. Ln a work conducted in parallel, we identified a new gene FANC, the REV7 gene. REV7 and RLV3 are two subunits of DNA polymerase is an error prone polymerase translesional involved in the synthesis of DNA and involved in the repair of DNA strand cross-bridges in combination with polymerase RFV I. The results of the genetic and functional analyzes establish REV7 as a FAN. Gene, involving for the first time a synthesis translesional gene, in addition to genes known in FA complex, D2/I and genes of homologous recombination
Marcheix, Bertrand. « Mise au point d'un modèle d'étude de la maladie vasculaire du greffon ». Toulouse 3, 2010. http://thesesups.ups-tlse.fr/892/.
Texte intégralBackground : In spite of progress in the field of immunosuppressive treatment, the allograft vasculopathy remains the first cause of graft loss after one year. The expérimental models appear essential for a better understanding of the implied mechanisms The traditional models are limited because of difficulties of transposition of the results to clinical situations in human. Goals : The goal of this work was to develop an original model to study AV consisting of the in vivo reconstitution in immunodeficient mice of human allogeneix conflicts. To achieve this goal, four intermediate stages were necessary : 1. The harvesting of human tissues in human cadaveric organ donors 2. The reconstitution of complete and functional human immune system in immunodeficient mice 3. The graft of human arterial grafts in mice 4. The reconstitution of expérimental groups (control, isogeneic, allogeneic) to valid the expérimental model of AV in allogeneic group and absence of AV in the control and isogeneic groups. Methods : The harvesting of human tissues in human cadaveric organ donors was organized in the whole Midi Pyrénées area after authorization of the ethic commitee of our insitution and of the French Transplantation Agency. Pièces of mesentery and segment of spleen were removed from the cadaveric organ donors. Defective SCID/Beige mice for immunity T, B and NK were used qfter checking of the absence of residual immunity (" leakiness "). A first part of this work focused on the reconsituttion of the human immune system in SCID/Beige mice : Mice were divided into 5 groups receiveing from 5 to 100 human illion splenocytes and into 2 groups receiving 5 to 10 million medullary cells. A weekly blood sample allowed typing of the circulating human cells (flow cytometry) and détection of human IgG (ELISA). After sacrifice, the lymphoid bodies were examined in immunohistochimy and flow cytometry. The second part of this work focused on the study of AV. SCID/Beige mice received infra rénal transplantation of segments of terminal collatéral of human mesenteric arteru using the " sleeve " anastomosis technique. Five to eight transplantation were carried out af in the 48 hours following each multi-organ harvesting. The transplantation was associated with an isogeneic immune reconstitution in 6 mice, while 12 mice underwent allogeneic reconstitution. .
Rederstorff, Mathieu. « Etude du rôle du sélénium et de la sélénoprotéine N dans les pathologies musculaires ». Université Louis Pasteur (Strasbourg) (1971-2008), 2006. https://publication-theses.unistra.fr/public/theses_doctorat/2006/REDERSTORFF_Mathieu_2006.pdf.
Texte intégralDelepine-Bellassen, Virginie. « Effets du vieillissement sur un modèle de mémoire épisodique ». Paris 6, 2011. http://www.theses.fr/2011PA066268.
Texte intégralKarine, Bourgade. « Propriétés anti-virales des peptides β-amyloïdes associés à la maladie d'Alzheimer : implication dans le développement et la progression de la maladie ». Thèse, Université de Sherbrooke, 2016. http://hdl.handle.net/11143/8198.
Texte intégralLapeyrière-Boissier, Odile de. « Les virus oncogènes à ADN : un modèle expérimental pour l'étude de la progression tumorale ». Aix-Marseille 2, 1987. http://www.theses.fr/1987AIX22018.
Texte intégralVirgili, Jessica. « Caractérisation d'un modèle murin transgénique de la maladie d'Alzheimer et de vieillissement accéléré ». Master's thesis, Université Laval, 2018. http://hdl.handle.net/20.500.11794/29574.
Texte intégralAging is central to the pathogenesis of Alzheimer’s disease, the most common form of dementia during the elderly. The incidence of sporadic AD is low before 65 years old; it then doubles every 5 to 6 years to surpass 8 cases per 100 personyears after 85. To model AD, numerous transgenic mice have been produced and characterized in the last decades. It was found that mice overexpressing mutated forms of the human amyloid-β (Aβ) precursor protein (hAPP) develop Aβ deposits in their brain, along with quantifiable memory deficits. Since the diagnosis of AD is dependent upon the histological visualization of both Aβ plaques and tau-laden neurofibrillary tangles, Dr LaFerla’s group (University of California, Irvine, USA) has developed the triple-transgenic model (3xTg-AD) expressing three mutant transgenes: Aβ precursor protein (APPSwe), presenilin-1 (PS1M146V), and tauP301L. This mouse line progressively develops both Aβ and tau pathologies in AD-relevant brain regions as well as deficits in synaptic plasticity and cognitive performance. However, the 3xTg-AD mouse does not develop frank neuronal loss as found in AD brain. A likely simple explanation is that, within the lifespan of a mouse, AD-relevant aging factors do not have the time to be fully expressed. To that aim, we crossed senescence-accelerated prone 8 mice (SAMP8) with 3xTgAD mice to produce senescence-accelerated 3xTg-AD mice with the hope to generate a model closer to the human disease. Our results indicate that senescence acceleration amplifies memory deficits and several AD-related neuropathological features -particularly the amyloid pathology- in female 3xTg-AD mice. Overall, the present data suggest that the SAMP8/3xTg-AD mouse is a valuable model combining aging factors and AD neuropathology, but also evidence complex interactions between genetic backgrounds, aging- and sex-related factors.
Laperine, Olivier. « La maladie parodontale : du développement d’un modèle animal à l’identification de cibles thérapeutiques ». Thesis, Nantes, 2016. http://www.theses.fr/2016NANT1034.
Texte intégralPeriodontitis is an inflammatory disease of bacterial origin, affecting the tooth-supporting tissues, the periodontium. This disease results from disproportionate immune response of the host against the bacterial stimulus, especially against Porphyromonas gingivalis (Pg). Inflammatory cascade is then triggered to ultimately activate osteoclasts. The pathophysiology of periodontitis remains elusive. Recently, the family of interleukin 1 was enriched with new members including interleukin 33 (IL-33), which plays a major role in innate immunity and in a pathology exhibiting strong similarities with periodontitis, rheumatoid arthritis (RA). IL-33 is highly expressed in the joints of these patients and invalidation of the gene encoding the receptor ST2 in a murine model of arthritis reduced bone loss associated with this disease. This thesis aims to determine whether IL-33 is expressed in periodontitis patients and in a mouse model of alveolar bone loss (alveolysis) induced by Pg. We recorded an overexpression of IL 33 by gingival epithelial cells in these patients as in the animal model. In this model, IL-33 expression is induced before the onset of alveolysis and increased the expression of the key osteoclastogenic factor RANKL. Other actors, in particular dendritic cells, could also promote this alveolysis upon the action of IL-33. These data suggest that IL-33 could be a major player in the pathogenesis of periodontitis
Ringuette, Goulet Cassandra. « Mécanismes d'action des immunoglobulines intraveineuses dans un modèle murin de la maladie d'Alzheimer ». Master's thesis, Université Laval, 2015. http://hdl.handle.net/20.500.11794/25945.
Texte intégralAffecting nearly 36 million people worldwide, Alzheimer's disease (AD) is a growing public health concern. AD is characterized by a progressive and irreversible slow deterioration of cognitive functions. The presence of postmortem amyloid plaques and neurofibrillary tangles is a hallmark of the disease. Despite recent advances in research, there is still no effective treatment for this disease. In recent years, intravenous immunoglobulin (IVIg) has shown some therapeutic potential for AD. The present work aims to determine the mechanisms of action by which IVIg exerts its beneficial effects in a mouse model of AD. Overall, my work has identified the inhibition of microglia activation as a possible mechanism of IVIg, allowing a decrease in brain inflammation and an increase in neurogenesis.
Puliti, Aldamaria. « Génétique moléculaire de la maladie de Hirschsprung : analyse d'un locus humain et d'un modèle murin de la maladie, le mutant "Dom" ». Paris 12, 1996. http://www.theses.fr/1996PA120037.
Texte intégralKamate, Caroline. « Influence de la réaction inflammatoire sur la progression tumorale : le modèle du mastocytome murin P815 ». Toulouse 3, 2002. http://www.theses.fr/2002TOU30188.
Texte intégralLefevre, Sophie. « Modèle levure de l'ataxie de Friedreich : stress oxydant, apoptose et dynamique mitochondriale ». Paris 6, 2010. http://www.theses.fr/2010PA066204.
Texte intégralTremblay, Marie-Ève. « Potentiel neuroprotecteur de la cystamine chez un modèle de souris parkinsonienne ». Master's thesis, Université Laval, 2007. http://hdl.handle.net/20.500.11794/19128.
Texte intégralDegiorgis, Laetitia. « Analyse des réseaux cérébraux par IRM chez un modèle souris de la maladie d’Alzheimer ». Thesis, Strasbourg, 2019. http://www.theses.fr/2019STRAD025.
Texte intégralAlzheimer’s disease (AD) is the most widespread dementia in the world, presenting progressive memory impairment. Using resting-state MRI, in both human and animal studies, has opened a new window into the brain and its connectome, proposing abnormal functional connectivity as a candidate biomarker of brain pathologies such as AD. We investigated the connectome’s affectation over time in vivo in a longitudinal study, to follow-up and characterize a transgenic mouse model of AD, combining both functional and structural approaches and evaluating possible network signatures of pathological states. We associate behavioral assessment and histological staining of neurotoxic protein to the MRI approach, in order to relate pathological mechanism, at both network and cellular level, to memory dysfunction. We found remarkable structural and functional modifications, mediating prodromal alterations of the memory system, before the beginning of memory impairment. Considerable changes in the septal connectivity particularly towards limbic centers but also involving communication with the Default Mode Network were highlighted over time. These vulnerable circuits represent biomarkers of the disease and potential targets for future treatment
Poyot, Thomas. « Etude de l'effet d'un facteur neurotrophique dans un modèle primate de maladie de Parkinson ». Paris 11, 2001. http://www.theses.fr/2001PA114822.
Texte intégralHeidari, Raheleh. « Modèle drosophile inductibles de pathologies à expansion de polyglutamine : applications au criblage génétique et pharmacologique ». Paris 7, 2014. http://www.theses.fr/2014PA077082.
Texte intégralPolyglutamine (PolyQ) diseases are a class of nine hereditary neurodegenerative diseases, including Spinocerebellar ataxia type 3 (SCA3) and Huntington's disease (HD), which are primarily caused by expansion of CAG repeats in coding region of their corresponding genes. Despite vigorous research on PolyQ, no efficient therapy is currently available for affected patients. In this thesis, we designed new Drosophila models of SCA3 and HD to identify new mechanisms involved in these diseases and used them in drug screening assays. As heart failure is a prominent cause of death in HD, we designed new heart models by overexpressing expanded (mHtt) or non expanded forms of Nter Huntingtin (Htt) fragments. Characterization of these models revealed significant cardiac hypertrophy that mimics the human HL phenotype. Using inducible systems we could identify critical stages for mHtt induced heart impairments. In addition we showed that treatment of flues with Methylene blue improves mHtt induced heart hypertrophy and cardiac function. We also characterized, in HD and SCA3 Drosophila inducible models within CNS, impairments of several physiological and behavioral parameters including average life span, circadian activity and rhythmicity, and sleep cycles. Characterization of these models allowed us to screen a number of genetic modifiers and a medium sized library of compounds. A proteomics study on a glial specific RD model was also performed. We discuss the new putative therapeutic targets identified by these three complementary approaches
Chenu, Chantal. « Origine et formation des ostéoclastes : étude à partir d'un modèle humain in vitro ». Lyon 1, 1990. http://www.theses.fr/1990LYO1T009.
Texte intégralCanaud, Guillaume. « Progression des maladies rénales chroniques : Rôle de la voie AKT/mTORC ». Phd thesis, Université René Descartes - Paris V, 2012. http://tel.archives-ouvertes.fr/tel-00922992.
Texte intégralBurbaud, Pierre. « Role du noyau sous-thalamique dans la physiopathologie de la maladie de Parkinson : étude d'un modèle expérimental chez le rat ». Bordeaux 2, 1993. http://www.theses.fr/1993BOR23069.
Texte intégralFerreira, Stéphanie. « Etude de l'apolipoprotéine E dans un modèle cellulaire de neurones humains : synthèses et toxicité de l'apolipoprotéine E au cours de la différenciation neuronale ». Lille 2, 2002. http://www.theses.fr/2002LIL2MT20.
Texte intégralDelord, Jean-Pierre. « Rôle de Her2 dans un modèle in vivo de maladie résiduelle de cancer de l'ovaire ». Toulouse 3, 2007. http://www.theses.fr/2007TOU30017.
Texte intégralBiological effect of HER2 in a model human ovarian carcinoma l malignancies in women. Although first-line chemotherapy induces complete clinical remission in many cases of epithelial ovarian cancer, relapse usually occurs 18–28 months from diagnosis due to micrometastases. The first part of our study was designed to aimed to evaluate the effect of trastuzumab on disease-free and overall survival in a specially designed murine model of ovarian cancer (OVCAR-3), which mimicked the natural history of human micrometastatic disease. Trastuzumab can cure the mice if started soon after induction chemotherapy. It can modestly inhibit the proliferation through mitogen-activated protein kinase (MAPK) signal transduction and clearly inhibit AKT phosphorylation, which is involved in survival pathway. As OVCAR-3 cell lines show no HER2 amplification nor overexpression, these results warrant further studies to assess the efficacy of trastuzumab in the early stage of relapse in cancer models other than those overexpressing HER2. .