Dissertationen zum Thema „Gliomes de haut grade“
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Dumont-Girard, Philippe. „Chimiothérapies intra-veineuses des tumeurs astrocytaires de haut grade : revue de la littérature et évaluation d'un protocole associant fotémustine, platine et VP16“. Montpellier 1, 1998. http://www.theses.fr/1998MON11064.
Der volle Inhalt der QuelleLaprie, Anne. „Imagerie métabolique par spectrométrie de résonnance magnétique des tumeurs gliales de haut-grade irradiées de l'adulte et de l'enfant“. Toulouse 3, 2007. http://www.theses.fr/2007TOU30332.
Der volle Inhalt der QuelleLeventoux, Nicolas. „Etude des foyers d’hétérogénéité tumorale dans les gliomes diffus de bas grade de l’adulte mutés IDH1“. Thesis, Montpellier, 2018. http://www.theses.fr/2018MONTT037.
Der volle Inhalt der QuelleGliomas are the main primary brain tumours affecting around 4000 new patients in France each year. Half of gliomas are detected in the advanced stage of glioblastoma (grade IV) while 15% of tumours are diagnosed in stage II (diffuse low-grade gliomas-DLGG). These tumors affect young patients and bear characteristic mutations, including a mutation for the enzyme IDH1 commonly found in secondary glioblastomas. These low-grade tumours are treated by surgery, ideally in awake condition but due to their diffuse nature, the residual part will progress inexorably to stage III or IV with overall survival between 5 and 15 years after diagnosis. Tumor progression is highly variable and unpredictable from one patient to another. Foci of tumor progression have been identified in 20% of patients with DLGG. These foci show a higher cell density and an increased Ki67. My thesis work consisted in studying the cellular and molecular changes associated with tumor progression. From the RNA profile of the foci and adjacent territories, I was able to highlight through high-throughput techniques significant decrease in gene expression in the foci, particularly of AGXT2L1/ETNPPL, carboxypeptidase E, EDNRB, SFRP2. I hypothesized that SFRP2 and ETNPLL could oppose cell proliferation and that their decrease would pave the way for tumor transformation. An inverse correlation between the amount of ETNPPL and the survival of patients with hepatocarcinoma has been published. By limiting the amount of phospholipid precursors in the cell, ETNPPL could act as a brake against proliferation and indeed, its decrease in glioma transformation foci could remove this inhibition. My PhD work will have been innovative in the comparative approach of the different tumors’ compartments for each patient studied and will have revealed ETNPPL as correlated to gliomagenesis and as potential therapeutic target
Ngwabyt, Bikeye Sandra-Nadia. „Etude par ARN interférence de l’expression du gène ASPM dans les cellules souches tumorales des gliomes de haut grade“. Thesis, Paris 11, 2011. http://www.theses.fr/2011PA11T030/document.
Der volle Inhalt der QuelleGlioblastoma (GBM) is the most frequent and aggressive form of primary brain tumors in adults; it is characterized by its resistance to current treatments (surgery, chemotherapy and radiotherapy). The prognosis is grim with a median survival of only 15 months underlining the importance to develop new therapeutic strategies. The recent development of the “tumor stem cell” (TSC) concept in hemopathies has been secondarily applied to gliomas with the identification of subpopulations of GBM cells which express neural stem cell markers and fulfill the criteria for stemness. Some evidences also suggest that this subpopulation could play a primary role in resistance to radio- and chemotherapy.ASPM (Abnormal Spindle Like Microcephaly Associated) is a protein regulating the proliferation of neuroblasts, highly expressed in the embryonic stage but weakly expressed in the adult brain. Preliminary reports suggesting that it could be involved in the development of gliomas (Horvath et al., 2007, Hagemann et al., 2008) prompted us to analyze further the role of this protein, focusing on its potential as a relevant candidate therapeutic target. In a series of 175 gliomas samples of various grades, we found that ASPM mRNA expression was strongly correlated with increasing tumor grade. We also found that ASPM expression increased at recurrence when compared to the initial lesion. Subsequently, we could demonstrate in vitro and in vivo that ASPM expression also increased over serial passages in gliomaspheres and in a mouse glioma xenograft model. In a therapeutic perspective, the effect of lentivirus-mediated shRNA post-transcriptional silencing of ASPM was evaluated in two different gliomasphere models and a dramatic proliferation arrest and cell death was observed. Taken together, these data suggest that ASPM is involved in the malignant progression of gliomas, possibly through expansion of a cancer stem cell compartment, and could be an attractive therapeutic target in glioblastoma multiforme.Another potential candidate tumor stem cell target in glioma is the sonic hedgehog pathway (hedgehog-Gli) which is required for GBM growth and stem cell expansion. In a collaborative study, it was found that NANOG, a transcription factor critically involved with self-renewal of undifferentiated embryonic stem cells, modulates gliomasphere clonogenicity, CD133+ stem cell behavior and proliferation. NANOG was regulated by hedgehog-Gli signalling and was essential for GBM tumourigenicity in orthotopic xenografts suggesting that it could also be a useful potential therapeutic target.Conclusions: Accumulating evidences suggest that tumor stem cells play an important role in the oncogenesis of gliomas and in their resistance to treatment. Our data support this concept and suggest that specific stemness markers may become useful targets to improve treatment of this devastating disease
Dembélé, Kléouforo-Paul. „Etude du rôle de protéines G dans les gliomes de haut grade : Implication dans la migration et le phénotype mésenchymateux“. Thesis, Normandie, 2019. http://www.theses.fr/2019NORMR077.
Der volle Inhalt der QuelleGBM is the most common (∼45% of all gliomas) and aggressive primary malignant brain tumor in adults. As described in this document's introduction, GBM highly heterogeneous phonotype associated with molecular signatures and gene expressions, but also with hypoxic and inflammatory microenvironmental conditions, contribute to frequent recurrence after complete resection-radio/chemotherapy, and explain the multiple therapeutic failures. Most of the current treatment options for GBM, although sometimes multimodal, the survival of GBM patients is not significantly improved, and the challenges to improve patient survival and quality of life remain enormous. Thus, the identification of differentially expressed factors that could better define the biological behavior of GBM, would provide a basis for the development of novel therapies and may be more effective. One of the characteristics of GBMs is their highly migratory and invasive properties, relayed mainly by chemotactic factors belonging to the hypoxic and inflammatory tumor microenvironment. G-protein coupled receptors (GPCRs) and their ligands, particularly the chemokines GPCRs, overexpressed in GBMs and stimulating migration, invasion and neoangiogenesis, play a key role in the development of GBM and the acquisition of an aggressive phenotype. In this context, our team demonstrated that UT, the receptor of urotensin II (UII), a pro-angiogenic and pro-inflammatory chemokine, as well as the well-known chemokine system SDF-1/CXCR4 are systematically co-expressed in GBMs particularly in vascular and perinecrotic areas and their expression are correlated with grade. We also demonstrated in vitro that UII/UT stimulate GBM cells chemotactic migration and invasion via activation of the pathways Gαi/PI3K and Gα13/Rho/ROCK, pathways that have previously been identified for the SDF-1α/CXCR4 system and other chemotactic GPCRs. In addition, a recent principal component analysis of TCGA (The Cancer Genome Atlas) database performed by Alexandre Mutel, PhD student in the team, has identified the expression signature of GPCRs in gliomas and particularly those which are overexpressed in mesenchymal GBM, among which many chemotactic GPCRs are included. Taking together, their redundant expression and signaling activity frequently associated with tumorigenesis, particularly in GBMs, raises the issue of studying signaling nodes common to all these GPCRs. These nodes, are primarily represented by heterotrimeric G proteins, composed of α, β and γ subunits, that couple these GPCRs relaying many intracellular secondary effectors, probably essentials in the regulation of GBM aggressiveness. In this context, the aim of my thesis work was to identify the main Ga, b and g subunits among the 31 G proteins expressed in human gliomas and those more specifically associated with the malignant grade, and the aggressiveness of GBMs and then to determine the role of one of these specific G proteins in GBM cells proliferation and invasion mechanisms. For that, we first analyzed the expression of the 31 subunits (15α, 5β and 11γ) of G proteins from the TCGA database and showed that the mRNA expression of Gαz, Gαi1, Gβ4, Gβ5 et Gγ3 are relatively low in GBMs while Gα12, Gα13, Gα15, Gαi2, Gαi3, Gβ2, Gγ5, Gγ11 and Gγ12 subunits, are particularly overexpressed in GBM and are associated with a poor prognosis in terms of recurrence and patient survival
Duval, Frédéric. „Etude rétrospective à propos de 67 cas d'astrocytomes de haut grade (janvier 1993 - Avril 1995 ) : de l'épidémiologie à la thérapeutique“. Bordeaux 2, 1996. http://www.theses.fr/1996BOR2M027.
Der volle Inhalt der QuelleNgwabyt-Bikeye, Sandra Nadia. „Etude par arn interférence de l'expression du gène aspm dans les cellules souches tumorales des gliomes de haut grade“. Phd thesis, Université Paris Sud - Paris XI, 2011. http://tel.archives-ouvertes.fr/tel-00633421.
Der volle Inhalt der QuelleNguyen, Aurélia. „Mécanismes de résistance à la chimiothérapie dans les gliomes de haut grade de l’enfant : implications des systèmes de réparation de l’ADN et de l’hypoxie intra-tumorale“. Thesis, Strasbourg, 2014. http://www.theses.fr/2014STRAJ086/document.
Der volle Inhalt der QuellePediatric malignant glioma (PMGs), are associated with a very dismal prognosis. They are distinct from their adult counterparts (AMGs), biologically but also clinically, with a lower response to temozolomide (the current reference alkylating chemotherapy) compared to AMGs. Temozolomide efficacy is reduced by the activity of the DNA repair enzyme, O6-methylguanine-DNA-methyltransferase (MGMT), whose expression is frequently silenced by promoter methylation. First, the development of a new methylation-specific PCR showed a lower frequency of MGMT methylation in PMGs (15%) vs AMGs (45%, p<0,001). Secondly, intra-tumor hypoxia and the upstream deregulation of mTOR-HIF-1α axis, well-known to be involved in chemo-resistance and the up-regulation of MGMT expression, were studied in a PMG cohort. The targeting of this axis was then studied in vitro using a therapy combining rapamycin and irinotecan. For this, pediatric patient-derived malignant glioma cell lines were developed
Perek-Courbon, Nathalie. „Etude des mécanismes cellulaires d'incorporation du Tc-99m-tetrofosmin dans un modèle de cellules tumorales gliales de haut grade : études comparatives avec le thallium 201 et le Tc-99m-setamibi“. Saint-Etienne, 1999. http://www.theses.fr/1999STET003T.
Der volle Inhalt der QuelleClement, Alexandra. „La caractérisation de la mutation IDH1R¹³²H dans un modèle de gliome humain de haut grade par imagerie multimodale, une étude translationnelle in vitro et in vivo“. Thesis, Université de Lorraine, 2020. http://www.theses.fr/2020LORR0213.
Der volle Inhalt der QuelleThe integration of molecular parameters in the classification of gliomas by the WHO in 2016, particularly IDH1R¹³²H mutational status, has significant diagnostic impact. This mutation is associated with a better prognosis but the physiopathological mechanisms underlying its expression remain poorly understood. Our work evaluates a multimodal imaging approach integrating multiparametric MRI and multiparametric multitracer PET to non-invasively characterize this mutation in gliomas. High grade human glioma cells (U87-MG) expressing or not the IDH1R¹³²H mutation (IDH1+ ; IDH1-), constructed using CRISP/Cas9 were studied in cell culture (in vitro), in a preclinical rat model after stereotactic grafting (in vivo) and after autopsy (ex vivo). In vitro, IDH1+ tumors expressed low levels of integrins αvβ3 and TSPO receptors which are considered to be biological markers of aggressiveness involving angiogenesis and tumor inflammation pathways. In vivo, MRIs (4.7T) of these IDH1+ tumors showed areas of high vascular densities which were characterized by functional neo-vascularizations, comparable to healthy cerebral vascular networks. Magnetic resonance spectra variations confirmed these results and revealed a less aggressive metabolite profile for these IDH1+ tumors. The combination of static and dynamic PET parameters with decreased uptake and a pronounced decrease in the PET slope of [⁶⁸Ga]NODAGA-(RGDyK)₂, as well as decreased PET uptake of [¹⁸F]DPA-714 in IDH1+ tumors, targeting αvβ3 integrins and TSPO receptors, yielded good diagnostic performances to discriminate the IDH1R¹³²H mutation. Ex vivo, spectroscopic analyses indicated less aggressive metabolic profile. This translational study demonstrates the benefits of multimodal and multiparametric imaging, and associates expression of the IDH1R¹³²H mutation, in high-grade human glioma cells with a less aggressive tumor profile. Validation of results from this pilot study in human primary cell cultures, may lead to a clinical multimodal imaging study to non-invasively characterize the IDH1R¹³²H mutation
Tellier, Anaïs. „Fonctions cognitives de patients atteints d'un gliome de haut grade avant tout traitement“. Mémoire, Université de Sherbrooke, 2016. http://hdl.handle.net/11143/9539.
Der volle Inhalt der QuelleVinchon-Petit, Sandrine. „Etudes précliniques sur la radiosensibilisation des tumeurs gliales de haut grade par chimiothérapie locale encapsulée“. Phd thesis, Université d'Angers, 2010. http://tel.archives-ouvertes.fr/tel-00585878.
Der volle Inhalt der QuelleVan, Praagh Isabelle. „La chimiothérapie intensive des gliomes malins de haut grade de l'adulte : à propos de 23 cas traités par BCNU à forte dose suivi d'autogreffe de moelle osseuse et de radiothérapie“. Clermont-Ferrand 1, 1991. http://www.theses.fr/1991CLF13021.
Der volle Inhalt der QuelleTourbez, Arthur. „Développement et caractérisation d'organoïdes de tumeurs cérébrales pédiatriques utilisés en recherche fondamentale et translationnelle“. Electronic Thesis or Diss., Lyon 1, 2023. https://n2t.net/ark:/47881/m6416x50.
Der volle Inhalt der QuellePediatric high-grade gliomas (pHGG) and posterior fossa type A ependymomas (EPN-PFA) remain one of the biggest challenges in pediatric oncology. They exhibit vast inter- and intra-tumoral heterogeneity, complicating the development of effective therapeutic strategies. Then to improve their clinical outcome, we absolutely need pre-clinical models that recapitulate key features of their corresponding parental tumors. During my PhD, I developed an optimized protocol for the establishment and biobanking of pHGG organoids (pHGG_O) and EPN-PFA organoids (EPN-PFA_O). These models can be grown long-term and comprehensive histological and molecular analyses showed that they recapitulate inter- and intra-tumoral heterogeneity of their parental tumor even after several passages and cryopreservation as 3D cultures. I further showed that they can be employed to test responses to standard of care therapy as well as new therapeutic options, including drugs from clinical trials as they accurately capture the clinical phenotypes of their respective parental tumors. Moreover, these models led to the identification of the DRD2 inhibitor ONC201 as an unexpected potential therapeutic agent for H3K27M non-altered pediatric brain tumors and helped identify combination strategies to increase the therapeutic response to ONC201. Thus, those models are positioned to support powerful and innovative preclinical studies, particularly those related to personalized assessments of treatment response profiles and identification of novel efficient drug combinations
Gerin, Chloé. „Modélisation et étude histologique de gliomes diffus de bas grade“. Phd thesis, Université Paris-Diderot - Paris VII, 2012. http://tel.archives-ouvertes.fr/tel-00820353.
Der volle Inhalt der QuelleGerin, Chloé. „Modélisation et études histologiques de gliomes diffus de bas grade“. Paris 7, 2012. http://www.theses.fr/2012PA077066.
Der volle Inhalt der QuelleDiffuse low-grade gliomas (LGG) are primary brain tumors. After a slow growth, they evolve to high-grade gliomas, resulting into death. These tumors are very diffuse, thus diffîcult to treat. A better knownledge of them could allow to cure them or, failing that, to optimize treatments. We studied the growth of LGG with a simple mathematical model, which led us to speculate (i) that they arise in adolescence, (ii) that the age of the tumor at diagnosis can be calculated easily, and (iii) that the growth rate is an important prognostic factor. This last prediction is consistent with clinical observations. To test this spatial model, we have quantitatively characterized biopsy tissues of human LGG, particularly the presence of edema. The microscopic analysis of these data underpins the idea that edema is the cause of the abnormality seen on T2-weighted MR imaging. To take this new result into account, we have incorporated edema into the initial model as a consequence of the presence of tumor cells. This model helps explain the long decay of the tumor radius for tens of months after radiation therapy: as tumor cells become less numerous, drainage of the edema becomes predominant. This model, which has only three free parameters, has been validated thanks to clinical data from twenty patients
Darlix, Amélie. „Gliomes diffus de bas grade : données épidémiologiques et hypothèses étiologiques“. Thesis, Montpellier, 2016. http://www.theses.fr/2016MONTT011/document.
Der volle Inhalt der QuelleThe epidemiology and risks factors of diffuse low-grade gliomas (DLGG, or WHO grade II diffuse gliomas) are yet poorly known. This thesis aimed at describing the epidemiology (incidence rates, demographic data) and at looking for arguments in favor of environmental, functional and molecular risk factors, in the literature and by our works. Descriptive epidemiology: The analysis of an exhaustive series of incident cases of DLGG diagnosed between 2006 and 2011 allowed the determination of DLGG incidence (incidence rate standardized on the French population: 0,775/105 person-years) as well as that of each histological subtype described by the 2007 WHO classification. Environmental risk factors: We were able to demonstrate significant differences in the geographical distribution of WHO grade II and III diffuse gliomas in metropolitan France, with higher incidence rates in the North-East and Center regions. This heterogeneity stands in favor of environmental risk factors, even though there is to date no proven environmental risk factor for DLGG. Biological risk factors: Our work demonstrated the existence of a clear dichotomy, regarding molecular biology, between frontal DLGG, more frequently IDH-mutated and 1p19q codeleted, and temporo-insular tumors, less frequently IDH-mutated and 1p19q codeleted, suggesting different gliomagenesis pathways for these two patterns of tumors. Functional risk factors: Finally, data from the literature provide two main arguments in favor of the existence of functional risk factors in DLGG. First, the intra-cerebral location of these tumors is specific and distinct from that of other gliomas, with a preferential implication of “functional” areas. Second, macroscopic intra-cerebral changes have been reported following training on specific tasks, or in relation with a specific expertise. The microscopic mechanisms that underlie these modifications are uncertain but an implication (direct or indirect) of glial cells seems probable, and could favor gliomagenesis. To date, only few studies have investigated the correlation between the subject’s activity and the risk of DLGG. We thus propose, following this thesis, a case-control study to further investigate this issue. In conclusion, even though there is no demonstrated risk factor for DLGG, data from the literature, and conclusions from the present work, suggest the implication of environmental, functional and biological factors in DLGG genesis
Lopes, Manuel. „Chirurgie des gliomes de bas grade en zone fonctionnelle : réflexions éthiques“. Paris 5, 2002. http://www.theses.fr/2002PA05N116.
Der volle Inhalt der QuelleTherapeutic controversies abouy low-grade gliomas arise both from the difficulties in clearly defining them from a histological point of view and from the subséquent imperfect knowledge of the natural history of the disease. The surgical attitude is thus heterogeneous ( from abstention to maximal possible resection involving in some cases functional areas), resulting from the difficulty in determining the best indication for each individual patient ; this lack of consensus generates several ethical issues. This fact has been assessed both practically
Alentorn, Agusti. „Caractérisation génomique et génétique des gliomes diffus de bas grade de l’adulte“. Thesis, Paris 11, 2014. http://www.theses.fr/2014PA11T011.
Der volle Inhalt der QuelleMultildimensional molecular characterization of tumors and more specifically of gliomas is of pivotal importance to identify: (i) new biomarkers (i.e. diagnostic, prognostic, theranostic or predisposing), (ii) new therapeutic targets and (iii) to improve our understanding of molecular oncogenesis.Our work has confirmed and consolidated previous data published in the literature, for example that: (i) 1p/19q co-deletion is associated with better prognosis, (ii) IDH mutation is associated with better prognosis, (iii) TP53 mutations and 1p/19q codeletion are mutually exclusive and (iv) PDGFRA is rarely altered, at genomic level, in low-grade gliomas (LGG).More originally, we have identified several genomic groups, with clinical and biological relevances, in LGG and more specifically in LGG without 1p/19q co-deletion: (i) 19q-deleted, (ii) 11p-deleted, (iii) 7-gained, (iv) 19-gained and (v) unclassified. Interestingly, 19q deletion abrogates the positive prognostic value of IDH mutation in LGG without 1p/19q codeletion.We have also identified new recurrent somatic gene mutations in LGG (i.e. TEP1 and RNF40 mutations), supporting the critical role of telomeres and chromatin remodelling in LGG.Finally, we have characterized further 11p-deleted LGG that exhibit mostly astrocytic phenotype and poor prognosis. This subgroup includes LGG overexpressing genes of inflammatory/immune cells (GIM -Glioma infiltrating microglia-, M1 macrophages and M2 macrophages) and infiltrated by macrophagic/microglial cells. This peculiar microenvironment detected in 11p-deleted LGG might be used as a therapeutic target. In conclusion, our work participates to characterize clinico-biological portrait of LGG and to describe a singular genomic subgroup of LGG characterized by 11p loss
Ben, Abdallah Mériem. „Un modèle de l'évolution des gliomes diffus de bas grade sous chimiothérapie“. Thesis, Université de Lorraine, 2016. http://www.theses.fr/2016LORR0215/document.
Der volle Inhalt der QuelleDiffuse low-grade gliomas are brain tumors of young adults. In this thesis, we focus on the segmentation and on the modeling of these tumors. In the first part of the manuscript, we study the segmentation of diffuse low-grade gliomas based on different manual and semi-automatic methods. The delineation of these tumors can be problematic because of their very infiltrating and inhomogeneous nature. In clinical practice, the monitoring of diffuse low-grade gliomas is based on the estimation of tumor volume, obtained either through a segmentation followed by a software reconstruction or through the three diameters method. As for the segmentation, it is manual and it is performed by practitioners on FLAIR-weighted or T2-weighted MRI.The three diameters approach is fast but it is difficult to implement in the case of highly infiltrating diffuse low grade gliomas or after a treatment. The manual segmentation and software-based volume reconstruction solution is time-consuming but it remains more accurate in comparison with the three diameters method. We investigate in this work the reproducibility of the manual segmentation with the OsiriX software by performing a subjective test in the Living Lab PROMETEE in TELECOM Nancy. The results of this study show that neither the practitioners' specialty nor their number of years of experience seem to have a significant impact on the quality of the segmentation. We also compare the results to those of a second test where we apply the three diameters method. Finally, we explore two semi-automatic segmentation algorithms which are, respectively, based on active contours and on the level set method. Even if automatic segmentation seems to be a promising avenue, we recommend for now the use of manual segmentation because of the diffuse nature of low-grade gliomas, which makes the tumor's contours complex to delineate. The second part of the manuscript is dedicated to the modeling of diffuse low-grade gliomas themselves or, to be more precise, to the modeling of the evolution of the tumor's diameter during chemotherapy. The therapeutic management of patients with these tumors often includes indeed chemotherapy. For this work, we focus on Temozolomide chemotherapy in first-line treatment. After the beginning of the treatment, the practitioners would like to determine the optimum time of discontinuation. We propose a statistical modeling of tumor diameter under chemotherapy. This modeling is based on linear and exponential regression models. It can predict the tumor diameter from a set of training dataset and can alert the clinician on the state of change in diameter under treatment. We hope that these models will, eventually, be used as a tool in the planning of chemotherapy in a clinical environment
Ben, Abdallah Mériem. „Un modèle de l'évolution des gliomes diffus de bas grade sous chimiothérapie“. Electronic Thesis or Diss., Université de Lorraine, 2016. http://www.theses.fr/2016LORR0215.
Der volle Inhalt der QuelleDiffuse low-grade gliomas are brain tumors of young adults. In this thesis, we focus on the segmentation and on the modeling of these tumors. In the first part of the manuscript, we study the segmentation of diffuse low-grade gliomas based on different manual and semi-automatic methods. The delineation of these tumors can be problematic because of their very infiltrating and inhomogeneous nature. In clinical practice, the monitoring of diffuse low-grade gliomas is based on the estimation of tumor volume, obtained either through a segmentation followed by a software reconstruction or through the three diameters method. As for the segmentation, it is manual and it is performed by practitioners on FLAIR-weighted or T2-weighted MRI.The three diameters approach is fast but it is difficult to implement in the case of highly infiltrating diffuse low grade gliomas or after a treatment. The manual segmentation and software-based volume reconstruction solution is time-consuming but it remains more accurate in comparison with the three diameters method. We investigate in this work the reproducibility of the manual segmentation with the OsiriX software by performing a subjective test in the Living Lab PROMETEE in TELECOM Nancy. The results of this study show that neither the practitioners' specialty nor their number of years of experience seem to have a significant impact on the quality of the segmentation. We also compare the results to those of a second test where we apply the three diameters method. Finally, we explore two semi-automatic segmentation algorithms which are, respectively, based on active contours and on the level set method. Even if automatic segmentation seems to be a promising avenue, we recommend for now the use of manual segmentation because of the diffuse nature of low-grade gliomas, which makes the tumor's contours complex to delineate. The second part of the manuscript is dedicated to the modeling of diffuse low-grade gliomas themselves or, to be more precise, to the modeling of the evolution of the tumor's diameter during chemotherapy. The therapeutic management of patients with these tumors often includes indeed chemotherapy. For this work, we focus on Temozolomide chemotherapy in first-line treatment. After the beginning of the treatment, the practitioners would like to determine the optimum time of discontinuation. We propose a statistical modeling of tumor diameter under chemotherapy. This modeling is based on linear and exponential regression models. It can predict the tumor diameter from a set of training dataset and can alert the clinician on the state of change in diameter under treatment. We hope that these models will, eventually, be used as a tool in the planning of chemotherapy in a clinical environment
Onken, Julia Sophie [Verfasser], und Peter [Akademischer Betreuer] Hau. „The role of the proteoglycan versican in high-grade gliomas / Julia Sophie Onken. Betreuer: Peter Hau“. Regensburg : Universitätsbibliothek Regensburg, 2013. http://d-nb.info/1033216631/34.
Der volle Inhalt der QuelleBergthold, Guillaume. „Genomic Profiling of Pediatric Low-Grade Gliomas“. Thesis, Paris 11, 2015. http://www.theses.fr/2015PA11T053/document.
Der volle Inhalt der QuelleLow-grade gliomas represent the most frequent brain tumor arising during childhood. They are characterized by a broad spectrum of tumor types.The definition of low-grade gliomas has been mainly based on morphology. This histological classification of pediatric low-grade gliomas (PLGG), suffers from the lack of reproducibility. The recent progress in molecular biology and genetics has brought new insights in the biology of those tumors and allows better understanding of their biology. This work provides a comprehensive analysis of two different genetic approaches in PLGGs. The first part is based on the description of somatic genetic alterations of the DNA. Using a large PLGG cohort, we have dissect the genome of those tumors and draw the landscape of their genetic alteration. Although BRAF and FGFR1 alterations are predominantly altered, we have discovered a new translocation, MYB-QKI, that is almost exclusively present in a specific histological subgroup; angiocentric gliomasThe second part of the thesis describes transcriptomic analysis of bulk PLGGs. This work describes molecular differences between PLGGs from distinct histologies and arising from different locations in the brain as well as different BRAF mutation status.We were also able to test single-cell expression analyses in three pilocytic astrocytomas (PAs) using RNA-sequencing. In this experimental work we have successfully tested the hypothesis that we can isolate single-cells from fresh PLGG tumors in order to analyze the trasncriptome at a large scale. We observed that single-cells expressing A2B5, a glial progenitor marker, isolated in pediatric PAs are characterized as a distinct biological population. These results underline the importance to improve the precision of the transcriptomic studies to capture the molecular signal of tumor cells and further understand the different pattern between normal cells and tumor cells
Mazzocco, Pauline. „Applications de la modélisation mathématique à l'optimisation des traitements chimiothérapiques des gliomes de bas-grade“. Thesis, Université Grenoble Alpes (ComUE), 2015. http://www.theses.fr/2015GREAM022/document.
Der volle Inhalt der QuelleLow-grade gliomas are slow-growing brain tumors, mainly affecting young adults who may remain without any symptoms for years. Patients can undergo surgery, or receive radiotherapy or chemotherapy with two different treatments: PCV of temozolomide (TMZ).In our different projects, we aim to show that mathematical modeling, and population approach, can allow to improve treatments, in terms of response duration and amplitude, for low-grade gliomas treated with chemotherapy (PCV and TMZ).In a first part, we focus on the possibility to modify PCV administration protocol, on a population level, to prolong tumor decrease duration. We claim that prolonging time interval between cycles enables us to significantly postpone the time to tumor regrowth.In a second part, we study the evolution of low-grade gliomas treated with TMZ. We analyze tumor size observations of 77 low-grade glioma patients, as well as genetic information, to develop a K-PD mixed-effects model describing tumor evolution before and after treatment onset. We then evaluate model capacity to predict tumor response duration and amplitude, on the base of early tumor sizes and genetic information. These predictions could be used to help clinicians to determine if they should prolong the treatment or not, for a given patient.In a last part, we more particularly focus on the phenomenon of resistance to TMZ. We build a PK-PD mixed-effects model describing the emergence of resistant tumor cells, using the same tumor size observations as previously. This model more accurately reproduces the evolution of TMZ in the body and its effect on the tumor. It is then used to optimize TMZ therapeutic protocol, on an individual level. Using an optimization algorithm, we determine the time interval between TMZ cycles, and the dose to administer, to prolong tumor decrease duration while limiting the emergence of resistance. The optimized protocols are evaluated with a stochastic approach, allowing to test the robustness of the model and the optimization.Through these different projects, we show the utility of mathematical modeling to help to improve chemotherapy treatments of low-grade glioma patients. We believe that these results could be transposed to other types of cancers
Perrillat-Mercerot, Angélique. „Modélisation et étude du métabolisme énergétique cérébral. Applications à l'imagerie des gliomes diffus de bas grade“. Thesis, Poitiers, 2019. http://www.theses.fr/2019POIT2285/document.
Der volle Inhalt der QuelleEverything that lives is born, eats, reproduces and dies. For the brain, the question is more complex because neurons have to survive and to support brain activity. Energy management is also particular because brain cells evolve together with no competition. Thanks to medical imaging, we know that neurons do not consume only glucose. They can use others energetic substrates such as lactate and glutamate as a power source.When a tumor appears, it changes the energetic metabolism to survive and support its own growth. In particular, cancer cells like to consume lactate. They also choose their favorite substrate based on the available oxygen. Modeling of energy substrates is useful to describe and predict energetic kinetics and changes. Mathematical models could get with clinical and medical results to describe, explain or predict low grade glioma dynamics. They can help to characterize and quantify a tumor evolution, then leading to improve their therapeutical management. Exchanges between mathematics and MRI (and MRS) enable to get accurate data and to build suitable mathematical models.This thesis deals with several approaches of substrates dynamics in healthy and gliomatous brains. These researches are based on systems of equations. We model local lactate exchanges (ODE, fast-slow systems), global substrates exchanges (ODE), glutamate/glutamine cycle (RDE) and local lactate exchanges in higher dimensions (PDE). We describe, analyze and give simulations of these models. Simulations are fitted on patient MRI data or literature data. Energy is necessary to live. But if your neighbor consumes a part of your resources, can you still survive ?
Tutto ciò che vive nasce, si nutre, si riproduce e muore. Per il cervello, la questione è più complessa perché i neuroni devono sopravvivere e sostenere l'attività cerebrale. La gestione energetica cerebrale è particolare anche perché le cellule cerebrali evolvono insieme, senza concorrenza. Inoltre, grazie alle immagini mediche, sappiamo che i neuroni non consumano solo del glucosio ma usano altri substrati energetici come il lattato o il glutammato.Quando un tumore si stabilisce, cambia il metabolismo energetico del cervello per sopravvivere e sostenere la propria crescita. In particolare, cellule tumorali consumano del lattato e scelgono il loro substrato preferito basandosi all'ossigeno disponibile.La matematica, e in particolare l'elaborazione di modelli matematici può aiutarci a ottimizzare i dati disponibili, che possono essere, di volta in volta, delle proprietà cellulare o delle lastre MRI o MRS. La modellizzazione dei substrati energetici potrebbe descrivere, spiegare o prevedere le dinamiche energetiche nel cervello.Questa tesi tratta di diversi approcci della dinamica dei substrati nei cervelli sani e gliomatosi. Queste ricerche si basano su sistemi di equazioni. Modellizziamo scambi locali di lattato (ODE, sistemi fast-slow), scambi globali di substrati (ODE), ciclo glutammato/glutammina (RDE) e scambi locali di lattato in dimensioni superiori (PDE). Descriviamo, analizziamo e diamo simulazioni di questi modelli. Le simulazioni sono adeguate su dati MRI paziente o dati di letteratura.Per vivere, l’energia è una necessità. Ma se i Suoi vicini consumassero le Sue risorse, riuscirebbe ancora a sopravvivere ?
Leidgens, Verena Jeannine [Verfasser], und Peter [Akademischer Betreuer] Hau. „In situ and in vitro profiling of brain tumour initiating cells of high-grade gliomas / Verena Jeannine Leidgens. Betreuer: Peter Hau“. Regensburg : Universitätsbibliothek Regensburg, 2016. http://d-nb.info/1100276777/34.
Der volle Inhalt der QuelleWager, Michel. „Statut moléculaire - oncogènes et gènes suppresseurs de tumeurs - des tumeurs gliales de l'adulte en relation avec le grade anatomo-pathologique et l'évolution tumorale“. Poitiers, 2007. http://www.theses.fr/2007POIT1401.
Der volle Inhalt der QuelleMutel, Alexandre. „La Filamine A, acteur central relayant les mécanismes d'invasion des gliomes de haut-grades : implication dans la signalisation et le trafic du récepteur chimiotactique de l'urotensine II Re-expression of Filamin A in glioblastoma promotes tne endogenous and chemokine receptor UT-induced migration/invasion : marker of aggressiveness and survival Association between vasoactive peptide urotensin II in plasma and cerebral vasospasm after aneurysmal subarachnoid hemorrhage : a potential therapeutic target“. Thesis, Normandie, 2019. http://www.theses.fr/2019NORMR081.
Der volle Inhalt der QuelleMultiform glioblastoma (GBM) are the most frequent and aggressive tumor of the central nervous system (CNS). The standard treatment therapy for GBM follows the “Stupp protocol”consisting in the most complete surgical resection combined with radio/chemotherapy with temozolomide (TMZ). Despite this heavy first line treatment, patients with GBM display a survival median of only 14.6 months. Even if the resection as large as possible, the diffuse properties of GBM cells leads to a quasi-systematic invasion of the margin of the resection cavity. The healthy brain parenchyma invasion by GBM cells, in margin or at distance of the resection cavity, constitutes a main therapeutic issue. These invasion mechanisms are carried by cell transformations caused by the microenvironment such as hypoxia and angiogenesis responsible for mesenchymal transition (MT) mainly controlled by two transcription factors STATγ and CEBPα which stimulate 70% of secondary mesenchymal genes. Hypoxia associated with MT triggers the expression of chemokine G protein-coupled receptor (GPCRs). The most studied chemotactic GPCR in GBM is CXCR4 which mediates promigratory effects through Gαi/PIγK/PIPγ and Gα13/Rho/ROCK as well as its endocytosis and recycling mediated by β-arrestins. Our team already demonstrated that the UT receptor of the neuropeptide urotensin II (UII) behaves like a chemokine receptor and stimulates GBM directional migrationby Gαi/PIγK/PIPγ and Gα13/Rho/ROCK allowing cell polarization, lamellipodia formation, actin stress fiber polymerization and cell contraction. Thus it appears that the expression and coupling redundancy of chemotactic GPCRs constitute a major brake for the development oftargeted therapy against these systems. Based on these observations, we proposed to identify new protein partners common to these chemokine GPCRs which could then be targeted by future anti-invasive therapies. First, we validated the systematic redundancy of expression of CXCR4/SDF-1α and UT/UII systems by immunohistochemical studies carried in various patient glioma grades (Collaboration with Pr A. Laquerrière, CHU Rouen Hospital). These systems are more strongly co-expressed in pseudopalisadic peri-necrotic hypoxic GBM areas. A two-hybrid screening of a bank of human brain cDNA allowed us to demonstrate that the 332-352 C-terminal amino acid sequence of UT interacts with the repeat D19-D20 domains of a platform protein called Filamin A (FlnA)
Guillevin, Rémy. „Contribution de la spectroscopie de résonance magnétique A l'investigation de l'histoire naturelle des gliomes de grade II OMS“. Amiens, 2009. http://www.theses.fr/2009AMIED010.
Der volle Inhalt der QuelleWHO grade II gliomas undergo to anaplastic transformation with variable delays, then making their natural history difficult to understand. Different approaches previously reported are exposed in the first part of this work. . However, specific biometabolic modifications leading to further glioma transformations have not been studied until now in a theoretical point of view. Using non invasive MR tools, as multinuclear spectroscopy and perfusion weighted imaging, we present in this work a mathemathical modelisation and conceptualization of WHO grade II gliomas biometabolic pathways
Collet, Solène. „L'IRM multiparamétrique et la TEP pour les gliomes : deux outils complémentaires pour la détermination du grade, l'évaluation de la survie et l'analyse spatiale“. Caen, 2013. http://www.theses.fr/2013CAEN3165.
Der volle Inhalt der QuelleImaging is used at different stages of management of glioma patients including conventional MRI. To better characterize this disease, more specific physiological and / or metabolical markers of tumor cells, vascularization or hypoxia mesured from multiparametric MRI (IRMmp) as perfusion (CBV), diffusion (ADC) and magnetic resonance spectroscopy (MRS) or PET with tracer [18F]-FLT and [18F]-FMISO. In this work, except FMISO, these imaging markers have been studied to determine the grade of gliomas and in relationship with the survival of patients with glioblastoma (GBM) to evaluate their diagnostic and prognostic value. Modalities for a better classification of tumor grade are the ADC and uptake [18F]-FLT. In addition, multivariate analysis also highlights the FLT PET and ADC as the best imaging biomarkers to predict survival. The analysis of the spatial relationships of various biomarkers in GBM shows that potentially aggressive areas, uptake of [18F]-FLT and vascularity are present outside areas of contrast enhancement usually treated. These could be incorporated to optimize the treatment of surgery and radiotherapy. These multimodal images also allow us to study the links between the different pathophysiological mechanisms and suggest that tumor proliferation is the cause of hypoxia and vasculature and that these two phenomena are spatially dissociated
LAGARDE, FERREYROLLES NATHALIE. „Lymphomes malins non hodgkiniens de haut grade de malignite de la sphere orl“. Amiens, 1994. http://www.theses.fr/1994AMIEM106.
Der volle Inhalt der QuelleLuherne, Viviane. „Reconnaissance des visages et des voix émotionnels dans une population adulte avec gliome et après accident vasculaire cérébral“. Thesis, Paris 8, 2015. http://www.theses.fr/2015PA080053/document.
Der volle Inhalt der QuelleEmotional domain was ignored for a long time, but today clinical neuropsychology acknowledges its overlapping with the cognitive domain and its importance in the follow-up of brain-damage patients, where difficulties in emotion recognition reduce the quality of interpersonal interactions and social cognition. The present thesis focuses on the recognition of five basic emotions (happiness, fear, anger, sadness, disgust) and of a neutral expression in two groups of patients with low-grade gliomas and post-stroke. The experimental protocol, which requires visual and auditory non-verbal processing, also includes a crossmodal condition. Three case studies of patients with gliomas allow us to refine our understanding of their emotional functioning. Our results show moderate visual and auditory difficulties in emotion recognition for both groups, with lower deficits in the glioma group than in the post-stroke group. These results confirm the relevance of a hodotopical view of the brain for emotional processes as in other cognitive domains. However, the behavioral benefit of crossmodal presentation observed in both groups is not sufficient to sustain normal results, which is likely to impact daily life. We highlight the necessity of evaluating emotion recognition as well as emotion experience in brain damage patients, in particular when they suffer from slowly infiltrating tumours
Moritz-Gasser, Sylvie. „Les bases neurales du traitement sémantique : un nouvel éclairage : études en électrostimulations cérébrales directes“. Thesis, Montpellier 1, 2012. http://www.theses.fr/2012MON1T007/document.
Der volle Inhalt der QuelleSemantic processing is the mental process by which we access to meaning. Therefore, it takes a central place in language comprehension and production, but also in the whole human functioning, since it allows conceptualizing and giving a meaning to the world, by confronting it consciously with the knowledge we store over our experiences. If the neural bases of semantic processing are well known at the cortical level, thanks to numerous studies based particularly on functional neuroimaging data, the analysis of the subcortical connectivity underlying this processing received so far less attention. Nevertheless, the authors agree on the existence of a semantic ventral stream, parallel to a phonological dorsal stream.The present work mean to bring a new highlight on the knowledge of the neural bases of semantic processing at the level of the single word, in connection with the wider setting of non verbal semantic processing, by the study of semantic skills in patients presenting with WHO grade 2 glioma, and for which they undergo a surgery in awaken conditions, with cortico-subcortical intraoperative mapping. Thus, this work highlights the crucial role of the inferior fronto-occipital fascicle, in this ventral semantic route, within a functional brain organization in parallel and distributed networks of cortical areas interconnected by white matter association fibers.it underlines also the interactive feature of cognitive functioning, and the significance of control mechanisms in language processing, as well as the measuring of mental chronometry when assessing it. These considerations lead us to propose a general hodotopical model of language anatomo-functional organization.The results presented in this work may thus have important clinical and scientific implications, regarding the comprehension of language brain functional organization, of its dysfunctioning, of functional reorganization mechanisms in case of brain lesion, and the elaboration of rehabilitation programs
Konnully, Augustus Meera Bessy. „Characterization of cellular heterogeneity in Diffuse Low Grade Glioma“. Thesis, Montpellier, 2020. http://www.theses.fr/2020MONTT038.
Der volle Inhalt der QuelleDiffuse Low-Grade Gliomas (DLGG) are WHO grade II glial tumors affecting younger adults. They are characterized as silent, slow growing tumors with fewer mitotic activities. However, they diffuse and invade the healthy brain via blood vessels and nerve fibers. These, over a period of years develop to malignant Glioblastoma, aggressive brain tumors where patients have an average medial survival of 12-15 months after diagnosis. Ill-defined phenotypic and cellular diversity of DLGG poses serious limitation to treatment and prevention at the early stage.In my PhD thesis, I aimed to address this limitation by characterizing the cellular heterogeneity in IDH1-mutated DLGG. By performing immunofluorescence analysis on grade II astrocytoma and oligodendroglioma, I have identified two largely non-overlapping cellular subpopulations expressing SOX9 and OLIG1 transcription factors, which represent astrocyte-like and oligodendrocyte-like cells, respectively. Upon further investigation, I have shown that these subpopulations express distinct molecular markers. Sox9 cells are associated with APOE, KCNN3, CRYAB and ID4, while Olig1 cells showed strong correlation with the expression of PDGFRA, SOX8, MASH1, and SOX4. In addition, the sox9 cells show a particular activation of signaling pathways including Notch, BMP and their downstream targets.To ascertain the role of Notch signaling in regulating the formation of these tumoral subpopulations, I used magnetic sorting of tumor cells from freshly resected glioma samples and overexpressed Notch Intracellular Domain (NICD), an active form of Notch. Increased Notch activation resulted in an upregulation of Sox9- and downregulation of Olig1-associated cell markers. I have then extended these analyses on one anaplastic IDH1 mutated patient derived cell line which reproduced similar gene expression profile confirming the robustness of the role of Notch signaling in regulating the plasticity of the cells. Parallel experiments performed by activation of Bone Morphogenetic Protein (BMP) signaling on IDH1 mutated cell line did not show a prominent effect on the plasticity. Nevertheless, BMP signal activation highly upregulated CRYAB, a SOX9 related marker and downregulated OLIG1 and OLIG2.In conclusion, I have identified two non-overlapping tumor subpopulations in diffuse low-grade gliomas and demonstrated the deterministic role of Notch signaling pathway in their formation. I believe that these findings would aid in better understanding tumoral heterogeneity in DLGG and be extended in designing new therapeutic strategies against these tumors
Lagaert, Jean-Baptiste. „Modélisation de la croissance tumorale : estimation de paramètres d'un modèle de croissance et introduction d'un modèle spécifique aux gliomes de tout grade“. Phd thesis, Université Sciences et Technologies - Bordeaux I, 2011. http://tel.archives-ouvertes.fr/tel-00652366.
Der volle Inhalt der QuelleLagaert, Jean-Baptiste. „Modélisation de la croissance tumorale : estimation de paramètres d’un modèle de croissance et introduction d’un modèle spécifique aux gliomes de tout grade“. Thesis, Bordeaux 1, 2011. http://www.theses.fr/2011BOR14308/document.
Der volle Inhalt der QuelleThis thesis deals with mathematical modeling of tumor growth. Firstly, we present a parameter estimation method. More precisely, it consists in recovering the position of the tumor blood vessel, starting from imaging. The first step is to design a particular vascularization, then we compute the tumor growth with this blood-vessel network by using a model based on partial differential equations and hence we try to recover the initial vascularization solving the inverse problem. We show that the estimated vasculature could be used to efficiently predict the future tumor growth. In the second part of this thesis, we introduce a class of models dedicated to glioma, adapted both to low grade and multiform glioblastoma. In order to take into account their specificities, we include mainly two effects in the model : on the one hand, the infiltrate behaviors of gliomas, and on the other hand, the impact of brain heterogeneity, of brain anisotropy and of brain geometry on the tumor growth. Our models allow us to evaluate the efficiency of anti-angiogenic drugs and to compare it with the effect of drugs inhibiting the invasion ability of glioma. The models have been implemented in 2D and 3D in actual geometry provided by an atlas
Lemaitre, Anne-Laure. „Métacognition et personnalité chez des patients porteurs d'un gliome diffus de bas grade : un eclairage nouveau sur le potentiel plastique du cerveau humain“. Thesis, Lille 3, 2019. http://www.theses.fr/2019LIL3H059.
Der volle Inhalt der QuelleRecent findings in the field of neuropsychology have allowed to move from a localized to a dynamic network approach of brain functions. This paradigmatic shift, from a static to a reshaping brain, has been supported by the investigation of patients with low-grade glioma, a neurological tumor known to trigger processes of compensation and rescue of brain functions. However, it is currently unestablished whether this neuroplastic compensation may extend to higher-order cognitive functions, specifically those involved in self-consciousness. By using both anatomo-functional correlational methods based on lesions localization and structural disconnection approach, the purpose of this work was to assess the extent to which the neurosurgical resections of low-grade glioma affect metacognitive processes and personality traits. First, we showed that frontal lobectomies, both unilateral and bilateral, did not induce metaperceptive impairments despite the established role of the prefrontal cortex in metacognition. Likewise, our results suggest that massive surgical resections did not significantly affect personality traits. However, some of them such as positive schizotypy, and a few behavioral modifications, such as anosognosia, were found to be associated with the disruption of some white matter bundles
Aubert, Agnès. „Imagerie fonctionnelle cérébrale et modélisation mathématique de la relation entre activité neuronale, métabolisme énergétique et hémodynamique : application à l'imagerie des gliomes de bas grade“. Paris 6, 2003. http://www.theses.fr/2003PA066353.
Der volle Inhalt der QuelleAura, Karine. „Protocole d'évaluation du langage fondé sur le traitement de fonctions prosodiques : étude exploratoire de deux patients atteints de gliomes de bas grade en contexte péri-opératoire“. Phd thesis, Université Toulouse le Mirail - Toulouse II, 2012. http://tel.archives-ouvertes.fr/tel-00798667.
Der volle Inhalt der QuelleBilat, Anne-Sophie. „Estimation du risque de rupture fragile de soudures de pipelines en aciers à haut grade : caractérisation et modélisation“. Phd thesis, École Nationale Supérieure des Mines de Paris, 2007. http://tel.archives-ouvertes.fr/tel-00186517.
Der volle Inhalt der QuelleGarnier, Camille. „Rôle de la protéine MAP3K8 et impact de la rigidité dans les cancers ovariens sereux de haut grade“. Thesis, Sorbonne Paris Cité, 2016. http://www.theses.fr/2016USPCC223/document.
Der volle Inhalt der QuelleOvarian cancers, which develop in a silent manner in the peritoneal cavity, resulting in a late diagnosis and a poor prognosis, urgently require new therapeutic strategies. In this context, my thesis aimed at better characterize the physical and biological properties of the High Grade Serous ovarian cancers (HGSOCs), accounting for 75% of the tumours.First, we found that the protein MAP3K8 accumulates in HGSOC and is a potential prognostic marker for these tumours. We demonstrated that MAP3K8 controls cancer cell proliferation and migration by regulating key players in Gl/S transition and adhesion dynamics. Importantly, we highlighted that MAP3K8 function is mainly mediated by the MEK pathway, and exhibits a predictive potential for MEK inhibitors, defining them as a promising therapeutic option, in combination with conventional therapy, for HGSOC patients.In a second part of my thesis, we showed that tumor stiffness is increased during tumor growth in HGSOC presenting a "Fibrosis" molecular signature. Moreover, tumor stiffening is associated with high stromal content and remodeling of the collagen network. Interestingly, the MEK kinase was specifically activated upon tumor stiffening. Furthermore, tumor stiffness accompanies a glycolytic metabolic switch, restricted to the central part of stiff tumors. Indeed, the periphery of stiff tumors remains softer than the central part with stromal cells secreting high levels of collagens and showing an OXPHOS metabolism. Thus, tumor stiffness could be at the crossroad of three major processes, i.e. matrix remodeling, MEK activation and stromal metabolic switch, that might explain, at least in part, the progression of HGSOC
Sauze-Fernandez, Samantha. „Rôle de l'enzyme d'amidation (PAM) et de l'Adrénomédulline dans le développement des tumeurs gliales humaines de haut grade de malignité“. Aix-Marseille 2, 2002. http://www.theses.fr/2002AIX20684.
Der volle Inhalt der QuelleAzar, Safa. „Tumeurs cérébrales de bas grade : élaboration de modèles in vitro et in vivo pour le développement de thérapies innovantes“. Thesis, Montpellier, 2017. http://www.theses.fr/2017MONTT017.
Der volle Inhalt der QuelleLow grade gliomas are low proliferating tumors affecting functional regions of young patients. In most cases, they tend to transform into a more malignant state following surgery. These tumors carry a key mutation in isocitrate dehydrogenase (70-80% of DLGG). Gliomas with IDH1 mutation have improved prognosis compared togliomaswith wild type IDH1. IDH1 protein acquires the ability to convert α-Ketoglutarate (α-KG) to 2-OH-glutarate (2-HG). The new onco-metabolite can interfere with the normal function of α-KG, leading to a general hypermethylation of the genome, thus inducing a blockage of the cellular differentiation. Very good reviews on the molecular mechanisms underlying high grade glioma invasion already exist but little is known about the cellular and molecular mechanisms in diffuse low grade gliomas. To that end, I characterized the profile of IDH1 mutated cells in the different types of DLGG. I have demonstrated that the tyrosine kinase, PDGFRα and EGFR receptors are abundantly expressed by tumor cells eventhough they are not activated. In contrast, a strong phosphorylation of Erk p42 / 44 proteins was detected in these tumors. This phosphorylation has a dual origin: tumor cells and their environment. The use of a series of markers allowed me to better define the state of differentiation of cancerous cells and to demonstrate a preferential expression of Sox8 in oligodendrogliomas while Sox9 is predominant in astrocytomas. In a second time, I have developed a method for the culture of low-grade diffuse gliomas and isolated five cell lines carrying the recurrent mutation IDH1 R132H. Recently Agios has identified very specific inhibitors (particularly AGI-5198) of the mutated IDH1 enzyme which, used in a murine glioma model, contributed to the demethylation of H3K9me3 histones with an increased expression of differentiation related genes as well as a reduction of the tumor mass. On the contrary, I have shown that AGI-5198 increases cell growth of patient cell lines, modifies the cellular migration and various signaling pathways.These studies shed new light on the phenotype of tumor cells, their diversity and The molecular mechanisms governing their proliferation
OLAGNIER, VALERIE. „Essai multicentrique en double aveugle ou cho-cell-gm-csf dans les neuroblastomes de haut grade traites par double autogreffe medullaire“. Lyon 1, 1989. http://www.theses.fr/1989LYO1M323.
Der volle Inhalt der QuelleMarrelec, Guillaume. „Méthodes bayésiennes pour l'analyse de la réponse hémodynamique et de la connectivité fonctionnelle en IRM fonctionnelle : apport à l'étude de la plasticité dans la chirurgie des gliomes de bas grade intracérébraux“. Paris 11, 2003. http://www.theses.fr/2003PA112260.
Der volle Inhalt der QuelleBOLD functional MRI (fMAI) is a recent imaging technique that can be used to dynamically and non-invasively study brain hemodynamic evolutions induced by neuronal activity. Use of fMRI could in particular allow for a better understanding of the plasticity phenomena that occur in the pathology of law-grade gliomas. To this end, development of new mathematical models is necessary. We first briefly introduce functional neuroimaging and the methodological framework of our work. We then develop our research on two complementary models, whose common goal is the study of brain plasticity. The first model considers the brain as a black box characterized by its response function, the so-called hemodynamic response. We proposed a robust Bayesian method to inter this response, through introduction of basic yet relevant a priori information about the underlying physiological process. This method was then generalized to account for most event-related fMRI acquisitions. A second model considers the interactions between regions involved in a given task. We developed a novel model, relying on the theory of independence graphs, that enables the quantification of interactions within this network. We also proposed a Bayesian procedure to estimate these quantities. We finally show that both approaches can be considered as two special cases within a more general model whose further development would allow for a better understanding of brain functional processes as measured by fMRI. Both methods developed were applied to clinical data to investigate brain plasticity observed among patients with law-grade brain gliomas. Most results obtained agree with the litterature. Some cast a new light on the functional reorganization that occurs among patients
Labreche, Karim. „Genetic Susceptibility and Molecular Characterization of Glioma“. Thesis, Université Paris-Saclay (ComUE), 2018. http://www.theses.fr/2018SACLS161/document.
Der volle Inhalt der QuelleGliomas are the most common adult malignant primary tumour of the central nervous system. Thus far, no environmental exposures has been linked to risk except for ionizing radiation, which only accounts for a very small number of cases. Direct evidence for inherited predisposition to glioma is provided by a number of rare inherited cancer syndromes, such as Turcot's and Li–Fraumeni syndromes, and neurofibromatosis. Even collectively, these diseases however account for little of the twofold increased risk of glioma seen in first-degree relatives of glioma patients. My research was centred on two complementary research activities: Identifying susceptibility genes for glioma to delineate key biological pathways contributing to disease pathogenesis and to identify new recurrent mutated genes for glioma to provide for further insights into glial oncogenesis and suggesting targets for novel therapeutic strategies. Collectively the findings in this thesis provide increased insight into the nature of genetic predisposition to glioma and substantiate the often distinct associations between susceptibility variants and glioma molecular groups. In addition the discovery of a new mutated gene in glioma offers the potential to support drug development and advance precision medicine for this tumours
Coget, Arthur. „Etude et modélisation de la plasticité cérébrale chez des patients porteurs de lésions gliales de bas grade opérés en chirurgie éveillée“. Thesis, Montpellier, 2020. http://www.theses.fr/2020MONTS053.
Der volle Inhalt der QuelleIntroductionDiffuse low-grade gliomas (DLGG) are slow-growing brain tumors occurring in young adults. This slow progression induces extensive neuroplasticity and explains why patients most of the time do not show any obvious neurological deficit at the time of diagnosis although tumors are located in ‘eloquent’ areas. Therefore DLGG provide an interesting model in understanding mechanisms of neuroplasticity.Awake surgery with direct cortical and subcortical electrostimulation mapping is recommended as first-line treatment of DLGG, allowing to maximize tumoral resection and limiting postoperative neurological deficit, maintaining patients quality of life.Resting-state fMRI, based on BOLD signal analysis, is used to study functional connectivity and neural plasticity. This technique allows robust evaluation of neural networks without performing a task. Consequently, it bypasses the impact of confusion, sedation or neurological deficits on task execution. In this thesis, we aimed to investigate perioperative functional connectivity modifications in order to evaluate neural plasticity after awake surgery.Subsequently we explained the functional results using multimodal MRI imaging to analyze anatomic connectivity and hemodynamic parameters.Methods82 patients with DLGG who underwent awake surgical resection were included in the principal study. MRI acquisitions were performed successively before, within 36 h after and three months post-surgery. All scans were executed on the same MRI magnet for each patient, i.e. either a 3.0 T magnet (Skyra, Siemens) or a 1.5 T magnet (Avanto, Siemens). First, data were preprossed using a standardized classical pipeline and analyzed with the CONN toolbox v16.a.Second, anatomic connectivity was evaluated using diffusion tensor imaging of the corpus callosum.Finally hemodynamic changes induced by surgery were assessed with traditional perfusion imaging as well as using an innovative analysis of the BOLD signal’ s temporal shift.ResultsSurprisingly, it was found that specifically a diffuse transient postoperative interhemispheric disconnectivity occurred between homologous regions, known as homotopic connectivity.In parallel, immediate and long-term postoperative alterations in the anatomic connectivity of the corpus callosum were observed. Immediate and long-term postoperative modifications were also found regarding both regional and global hemodynamics characteristics. Yet, no significant link between the homotopic connectivity findings and the anatomical and hemodynamic changes could have been established at this point.Nevertheless, the hemodynamic analysis allowed the identification of a a specific brain region : the striatum. It was hypothesized that it acts as a central region for the maintenance of homotopic connectivity, explaining simultaneously the decreased post-surgical homotopic connectivity observed.ConclusionThe highlighted transient postoperative functional homotopy is probably due to multifactorial causes To start entangling these causes, the use of anatomic and hemodynamic imaging data analyses seems crucial to interpret functional connectivity data both immediate and long-term postoperative.Cerebral vasoreactivity and modelling studies provide thereby a very promising tool to better understand the interrelated processes underlying postoperative functional connectivity modifications
Bascou, Jérôme. „Relations entre microstructures, mécanismes de déformation et propriétés physiques anisotropes des roches de haut grade de métamorphisme : étude de quelques éclogites et granulites“. Montpellier 2, 2002. http://www.theses.fr/2002MON20118.
Der volle Inhalt der QuelleCorre, Frédéric. „Leucémie à tricholeucocytes associée à un lymphome malin non-hodkinien (sic) de haut-grade de malignité : à propos d'un cas, revue de la littérature“. Bordeaux 2, 1999. http://www.theses.fr/1999BOR2M069.
Der volle Inhalt der QuellePLUTA, ERIC. „Evaluation du cout du traitement d'induction des lymphomes malins non hodgkiniens de haut grade de malignite de l'adulte avec ou sans facteurs de croissance hematopoietiques“. Reims, 1993. http://www.theses.fr/1993REIMM058.
Der volle Inhalt der Quelle