Дисертації з теми "Ependymomas"
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1
TIXIER, THIERRY. "Les ependymomes sous-cutanes sacrococcygiens." Clermont-Ferrand 1, 1990. http://www.theses.fr/1990CLF13076.
2
Eicker, Monika. "Monosomie 22 in Ependymomen." [S.l. : s.n.], 2007. http://nbn-resolving.de/urn:nbn:de:bsz:289-vts-58938.
3
Kilday, John-Paul. "Genomic and epigenetic characterisation of childhood ependymoma." Thesis, University of Nottingham, 2011. http://eprints.nottingham.ac.uk/12553/.
Анотація:
Paediatric ependymomas remain a clinical management challenge, with a relatively poor prognosis when compared to other childhood tumours of the central nervous system. An improved understanding of underlying ependymoma biology may identify new correlates of outcome and potential therapeutic targets. To address this, AffymetrixTM 500K SNP arrays were used to establish the nature and range of genomic imbalances in 63 paediatric ependymomas (42 primary and 21 recurrent). Over 80 % of tumours were analysed against patient-matched constitutional DNA. In addition, the Illumina® GoldenGate® Cancer Panel I array was used to identify differences in methylation profile across 98 paediatric ependymomas (73 primary and 25 recurrent). While collective assessment revealed the most common anomalies, specific aberrations were characteristic of certain ependymoma subgroups, particularly those relating to tumour location, patient age, disease recurrence and patient prognosis. The genomic imbalance of 15 selected candidate genes (NSL1, DNAJC25, NAV1, CDKN2A, CHI3L1, HOXA5, TXN, BNIPL, and PRUNE) were confirmed by quantitative Polymerase Chain Reaction. Genomic gain involving regions of chromosome 1q were associated with an unfavourable patient outcome, such as the focal locus on 1q21.3 encompassing PRUNE. The genomic gain of PRUNE correlated with an increased encoded protein expression, as assessed by immunohistochemistry (IHC). This adverse prognostic association with 1q was upheld in the subsequent part of this work. Fluorescent in situ hybridisation and IHC were used to evaluate a panel of six putative prognostic markers (1q25 gain, PRUNE, Tenascin-C, Nucleolin, Ki-67 and NAV1 expression) across a paediatric intracranial ependymoma tissue microarray cohort of 107 primary tumours treated within the confines of two aged defined clinical trials (UK CCLG 1992 04 and SIOP 1999 04). Within the younger UK CCLG 1992 04 cohort, copy number gain of chromosome 1q25 and PRUNE overexpression were independently associated with an increased risk of disease progression, while strong PRUNE expression was also an independent marker of worse overall survival. In addition, increased Tenascin-C expression correlated with a reduced overall survival on univariate analysis. For older children in the SIOP 1999 04 cohort, strong PRUNE expression in ependymomas was again identified as an adverse prognostic marker, correlating with increased mortality on univariate assessment.
4
Tourbez, 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.
Анотація:
Les gliomes de haut grade pédiatriques (pHGG) et les épendymomes de la fosse postérieure de type A (EPN-PFA) représentent l'un des plus grands défis de la neuro-oncologie pédiatrique. Leur singularité se manifeste par une remarquable hétérogénéité inter- et intra-tumorale qui complique le développement de stratégies thérapeutiques efficaces. Afin d'améliorer les perspectives cliniques pour les patients atteints de ces cancers, il est impératif de disposer de modèles pré-cliniques capables de refléter fidèlement les principales caractéristiques de leurs tumeurs d'origine. Au cours de mon doctorat, j'ai élaboré un protocole pour la création et la conservation de tumoroïdes pHGG (pHGG_O) et de tumoroïdes de EPN-PFA (EPN-PFA_O). Ces modèles peuvent être cultivés plusieurs mois/années. De plus, des analyses histologiques et moléculaires approfondies ont permis de montrer que ces modèles préservent l'hétérogénéité inter- et intra-tumorale de leur tumeur d'origine, et ce même après plusieurs passages en culture et cryopréservation. J'ai également démontré que ces modèles peuvent servir à l'évaluation de la réponse aux traitements qui reste comparable à celle observée chez les patients. De plus, ces modèles ont révélé leur potentiel pré-clinique (1) en permettant d'identifier l'ONC201, un inhibiteur de DRD2, comme un agent thérapeutique d'intérêt pour les tumeurs H3K27 nonaltérées, et (2) en contribuant à élaborer des stratégies de combinaison visant à amplifier la réponse thérapeutique à l'ONC201. Ces modèles sont donc des outils pré-cliniques robustes et puissants, en particulier pour l'appréciation des profils de réponses aux traitements et la recherche de nouvelles combinaisons de médicaments efficacesPediatric 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
5
Sabnis, Durgagauri. "An investigation of druggable prognostic markers in paediatric ependymoma." Thesis, University of Nottingham, 2016. http://eprints.nottingham.ac.uk/33243/.
Анотація:
Background: Paediatric ependymomas are the second most common malignant brain tumours in children. Tumour recurrence, chemoresistance and invasion of surrounding critical structures are the hallmarks of ependymomas. These features are consistent with the cancer stem cell (CSC) hypothesis which states that tumours harbour a sub-population of stem-like cells which underlie therapeutic resistance. This study investigates the role of the radial glial stem cell marker BLBP, the multidrug transporter ABCB1, and the DNA repair enzyme MGMT in therapy failure in ependymomas with particular emphasis on the role of CSCs. Material and Methods: Database analyses were performed to assess the expression of the aforementioned markers in patients from 3 publicly available gene expression datasets. Furthermore, samples from 2 European paediatric ependymoma trial cohorts were screened for ABCB1, BLBP and MGMT expression by immunohistochemistry to elucidate their prognostic value. The expression of these markers was also determined in a panel of 5 ependymoma derived cell lines by QRT-PCR or western blotting analysis. Roles in chemoresistance (clonogenic & cytotoxicity assays) and tumour invasion (wound healing & 3D invasion assay) were then investigated. Results: Poor survival in the chemotherapy-led paediatric ependymoma CNS9204 trial was significantly associated with ABCB1 (P=0.007) and BLBP (P=0.03) expression whilst MGMT (P<0.001) and BLBP (P=0.002) expression predicted poor survival in the radiotherapy-led CNS9904 trial cohort. ABCB1 and BLBP expression was consistent with the CSC hypothesis whilst MGMT was expressed in both CSCs as well as the tumour bulk. Inhibition of ABCB1 and BLBP, with the phosphodiesterase-5 inhibitor vardenafil and PPAR-ϒ antagonist GW9662 respectively, potentiated response to chemotherapy and also inhibited the ability of ependymoma cell lines to migrate and invade. Finally, whilst each of the tested cell lines were resistant to the alkylating agent temozolomide, they were sensitive to the novel N3-propargyl analogue of temozolomide. Conclusion: ABCB1, BLBP and MGMT were not only markers of robust prognostic value but they also contributed functionally to the aggressive behaviour of ependymoma. Inhibition of ABCB1 and BLBP by vardenafil and GW9662 may represent effective approaches to overcome chemoresistance and invasion in ependymoma patients. The N3-propargyl analogue of temozolomide could also represent a novel treatment option for MGMT expressing ependymoma patients.
6
TALIK, ZYGART NATHALIE. "Les ependymomes intracraniens de l'enfant : a propos de 27 observations." Lille 2, 1989. http://www.theses.fr/1989LIL2M382.
7
Andreiuolo, Felipe. "Target in context : molecular pathology of pediatric ependymoma and high grade glioma." Phd thesis, Université Paris Sud - Paris XI, 2012. http://tel.archives-ouvertes.fr/tel-00913042.
Анотація:
Biomarkers for the classification, clinical management and prognosis of pediatric brain tumors (ependymoma and high grade glioma, (HGG)) are lacking. To address this, biomarkers were developed and explored in view of classification, prognostication, target identification and prediction of the efficacy of treatment for patients with such tumors.We show that overexpression of neuronal markers distinguishes supratentorial from infratentorial ependymoma, and among the former higher immunoexpression of neurofilament 70 (NEFL) is correlated with better progression free survival (PFS). Tenascin-C (TNC) is significantly overexpressed in infratentorial ependymoma. A multi-institutional European ependymoma collaboration group was established and analyses were performed in a pediatric cohort of 250 patients, where immunohistochemistry (IHC) for TNC showed to be a robust marker of poor overall survival (OS) and PFS, particularly among children under 3 years, this being further validated in an independent cohort. Techniques and scoring performed in different laboratories were highly reproducible. IHC for NEFL and TNC could be used for prognostication of pediatric ependymoma.The analysis of putative predictive markers for the response to targeted therapies in pediatric HGG in the setting of a clinical trial with the anti-EGFR agent erlotinib was performed by IHC and fluorescent in situ hybridization. The frequent loss of PTEN in diffuse intrinsic pontine glioma (DIPG) and the confirmation of the biological singularity of the certain subgroups (expressing EGFR, displaying oligodendroglial differentiation) which seem to be associated with better response to erlotinib have helped our group to establish the design of the next Phase III protocol for this disease at our institution. We report mutations in PI3KCA constituting the first identification of oncogene mutations in some DIPG, which further highlight their biological heterogeneity. Further studies are needed to define the interaction between PTEN loss, EGFR overexpression, oligodendroglial differentiation, PI3KCA mutations and other recent findings such as PDGFRA/MET gains/amplification and TP53 mutations in these heterogeneous lesions and their relationship to the outcome of patients under new targeted therapies for this largely fatal disease.This thesis has allowed us to explore the molecular pathology in the context of biology and clinical setting of pediatric brain tumors.
8
Feuß, Mareike [Verfasser]. "Die mikrochirurgische Therapie des cerebralen und spinalen Ependymoms / Mareike Feuß. Medizinische Fakultät." Bonn : Universitäts- und Landesbibliothek Bonn, 2011. http://d-nb.info/1017916136/34.
9
LABORIEUX, ANY. "Ependymomes intracraniens de l'enfant : revue de la litterature a propos de deux cas." Nice, 1990. http://www.theses.fr/1990NICE6531.
10
GENESTIN, ELISABETH. "Ependymome pan-medullaire : etude clinique du 7eme cas de la litterature, et apports des techniques nouvelles." Lille 2, 1989. http://www.theses.fr/1989LIL2M241.
11
Ritzmann, Timothy. "Recurrent paediatric ependymoma : a multicentre analysis of clinical features and tumour biology in the molecular era." Thesis, University of Nottingham, 2018. http://eprints.nottingham.ac.uk/51719/.
Анотація:
Introduction: Ependymoma is the second most common malignant brain tumour of childhood. 50% of children with primary disease recur; three-quarters of these do not achieve long term survival. In the ‘molecular era’ of cancer research, diagnosis combines advanced molecular profiling with histopathological assessment. Whilst primary ependymomas can be classified based on epigenetic and transcriptomic features, there is little information on molecular signatures at recurrence. However, some small studies have implicated cancer immunity. Trials of novel therapies at recurrence have been disappointing. This study undertook molecular profiling of recurrent ependymoma, combined with contemporary clinical data, to better understand recurrence biology and potential therapy options. Methods: Clinical outcomes for 188 children with recurrent ependymoma were analysed. Cases with primary and matched recurrent samples were included in DNA methylation (n=56), RNA sequencing (n=52) and immunohistochemical (IHC) (n=56) analyses. RNA sequencing from FFPE tissue was validated to expand the cohort. Results: Recurrence was the strongest predictor of long term survival. Treatment approach at primary diagnosis was not associated with survival, but radiotherapy at first recurrence was associated with better short-term outcomes. Children with the commonest DNA methylation based diagnoses, EPN_PFA and EPN_RELA, had equally poor outcomes. RNA sequencing from FFPE tissue was effective, therefore tumours sequenced from FFPE and FF tissue were included in paired gene expression analyses. Transcriptomic and DNA methylation analyses identified three similar subgroups in FFPE and FF cohorts (PF1, PF2 and ST). At first recurrence, PF1 was associated with downregulated immune and inflammatory ontologies, which may indicate tumour immune escape. PF2 and ST subgroups demonstrated upregulation of ontologies associated with adaptive immunity. Despite this, there was little evidence of change in either immunogenicity or T-cell effector activity at first recurrence. IHC analysis identified a fall in inflammatory cells in posterior fossa tumours at recurrence and indicated that ependymoma is an immune excluded tumour. Conclusions: This study highlights both the abysmal prognosis for this disease, and the need for a better understanding of tumour biology to improve outcomes. This study has contributed novel data on changes at recurrence across molecular subgroups, and identified the immune excluded nature of ependymoma, which may be important in guiding therapy. The validation of RNA-seq from FFPE in childhood brain tumours has facilitated access to a large set of previously uninvestigated samples.
12
Szathmari, Alexandru. "Étude du transcriptome dans les tumeurs périventriculaires du système nerveux central : recherche des marqueurs diagnostiques et pronostiques." Thesis, Lyon 1, 2010. http://www.theses.fr/2010LYO10037.
Анотація:
Les services de Neurochirurgie du Groupement Hospitalier Est de Lyon ont une expérience reconnue pour l’exérèse des tumeurs des régions périventriculaires du système nerveux central notamment au niveau de la région pinéale. Dans ce contexte neurochirurgical favorable et avec l’opportunité d’utiliser des techniques de biologie moléculaire, notre objectif a été l’identification de marqueurs diagnostiques pour chaque type tumoral par une étude transcriptomique en microarray, la caractérisation d’un sous-type de tumeur du parenchyme pinéal (TPP) pléïomorphe, l’évaluation de la synthèse de mélatonine par les TPP et l’étude du transcriptome de certains organes circumventriculaires (OCV) microdisséqués chez le rat. L’analyse du transcriptome des tumeurs périventriculaires a permis de regrouper les tumeurs par leur signature moléculaire et d’identifier des marqueurs diagnostiques pour chaque type tumoral. De nouveaux marqueurs pronostiques potentiels (HoxD13, Prame, CD24 et Pou4f2 et gènes de la voie Aurora kinase B) sont proposés en vue d’améliorer la classification des TPP. Pour ces dernières, une étude multicentrique a permis de caractériser un sous-type tumoral, les tumeurs pléïomorphes, souvent surgradées. L’étude des TPP ex vivo et in vivo montre leur capacité de synthèse de mélatonine. Toutefois, nous n’avons pu obtenir une lignée de cellules tumorales stable. La microdissection des OCV du rat, parfois vestigiaux chez l’homme et qui pourraient être à l’origine de tumeurs périventriculaires, a permis d’étudier leur transcriptome et de mettre en évidence des marqueurs nouveaux ou déjà associés dans la littérature à ces structuresNeurosurgery of periventricular tumors, especially of pineal region tumors, is well developed at the Neurosurgical Hospital in Lyon. Taking opportunity of this background, our objective was identification of new diagnostic markers for each of these tumors using microarray transcriptome analysis, characterisation of a pleomorphic pineal parenchyma tumor (PPT) subtype, evaluation of melatonin synthesis in PPTs and the microarray analysis of molecular signature of some of circumventricular organs (CVO) after their laser microdissection in rat. The microarray analysis of periventricular tumors allowed molecular classification of the tumours and revealed different diagnostic markers for each type of tumors. Potentially new prognostic candidate genes (HoxD13, Prame, CD24 and Pou4f2 and Aurora kinase B pathway genes) are proposed for improvement of PPT classification. A PPT multicenter study allowed the characterisation of a pleomorphic subtype frequently managed as a higher grade tumour in the literature. The study of PPT ex vivo and in vivo showed their preserved capacity for melatonin production. However a stable PPT cell line culture could not be obtained. The laser microdissection of OCV in rat, sometimes vestigial in humans and potentially at the origin of the periventricular tumors, associated with a microarray study highlighted some potentially new or already described specific markers of these structures
13
Bonhns, Michalowski Mariana. "Étude des altérations épigénétiques des tumeurs des enfants : le cas des épendymomes et des neuroblastomes." Université Joseph Fourier (Grenoble), 2006. http://www.theses.fr/2006GRE10210.
Анотація:
Au cours des dernières années, un nouveau mécanisme du développement tumoral a été décrit; l'hyperméthylation des gènes suppresseurs de tumeur (GST). Les modifications « épigénétiques » ont été peu étudiées dans les cancers de l'enfant et aucune grande série de tumeurs pédiatriques existait avant 2002. Nous avons recherché ce type altérations dans deux groupes de tumeurs de l'enfant: les ependymomes et les neuroblastomes. Les ependymomes (EP) représentent la troisième tumeur la plus fréquente du système nerveux central (SNC) de l'enfant et n'a pas de marqueurs biologiques pronostiques identifiés. Le neuroblastome, quant à lui, est la tumeur solide extra crânienne la plus fréquente chez l'enfant et présente des anomalies génétiques et moléculaires qui ont été clairement liées au pronostic. Nos objectifs étaient de décrire un profil de méthylation de ces deux cancers de l'enfant et chercher des relations possibles avec l'évolution clinique. Dans la première étude, une série de 27 enfants avec un EP intracrânien et 7 avec papillome du plexus choroïde a été étudiée. Nous avons décrit et comparé le statut de méthylation de 19 gènes. Dans la deuxième étude, 62 neuroblastomes (NB) ont été évalués pour le statut de la méthylation de ces gènes. Nous n'avons pas trouvé de relation statistiquement significative entre la méthylation et l'évolution clinique, mais les méthylations ne semblent pas être distribuées sous une forme aléatoire dans les EP et les NB et peut représenter un mécanisme de développement et d'évolution tumorale. L'hyperméthylation a été corrélée au stade clinique des NB: stades 1, 2 et 4s étaient moins fréquemment méthylés que les stades 3 et 4 (p = 0. 002). En conclusion, les résultats de nos séries indiquent que la méthylation des gènes suppresseurs peut avoir un rôle dans l'évolution et le développement des cancers de l'enfant. L'étude des altérations épigénétiques est nécessaire pour améliorer la comprehension des mécanismes de la carcinogenèse dans les tumeurs pédiatriques. Ces altérations pourraient, donc, être utilisées comme des marqueurs de maladies ou d'évolutivité et les gènes méthylés pourraient être considérés comme des nouvelles cibles thérapeutiquesDuring the last 10 years, a new mechanism of tumor development has been described: the hypermethylation of tumor suppressor genes. These epigenetic modifications were rarely studied in childhood cancer and large series of patients didn't exist before 2003. We studied two groups of childhood tumors; ependymoma and neuroblastome. Ependymomas (EP) represent the third most frequent type of central nervous system (CNS) tumor of childhood. No prognostic biological markers are available, and differentiation from choroid plexus papilloma (CPP) is difficult. On the other hand, neuroblastoma, the most common extracranial solid cancer diagnosed in infancy and childhood, has some genetic abnormalities that are clearly related to prognosis as NMYC amplification. Our objectives were to describe a methylation profile in these two childhood cancers and try to find a relationship between genes methylation and clinical evolution. In the first study, for a sample of 27 children with intracranial EP and 7 with CPP, we described and compared the methylation status of 19 genes. On the second study, 62 neuroblastomas were studied in terms of the methylation status of the same genes. Although we did not observe a statistical relationship between methylation and clinical outcome, the methylation pattern does not appear to be randomly distributed in ependymoma and in neuroblastoma and may represent a mechanism of tumor development and evolution. Hypermethylation was related to clinical stage in neuroblastoma: stages 1, 2 and 4s were less frequently methylated than those at stages 3 and 4 (p = 0. 002). In conclusion, the results from our series indicate that hypermethylation of tumor suppressor genes may be important in the development and evolution of childhood cancers. Thus, these epigenetic alterations could be used as a marker of the disease and genes regulating methylation should be considered as possible novel therapeutic targets
14
Sander, Milena Lucia [Verfasser], and Matthias [Akademischer Betreuer] Reinhard. "Zerebrale Hämodynamik nach Schädelbestrahlung im Kindesalter bei Patienten mit Medulloblastom oder anaplastischem Ependymom." Freiburg : Universität, 2020. http://d-nb.info/1205256598/34.
15
Diop, Seynabou. "Étude de la contribution maternelle d'EZHIP à la distribution de H3K27me3 au cours du développement précoce de la souris." Electronic Thesis or Diss., Sorbonne université, 2022. https://accesdistant.sorbonne-universite.fr/login?url=https://theses-intra.sorbonne-universite.fr/2022SORUS544diff.pdf.
Анотація:
La machinerie Polycomb, par ses activités de régulation de la chromatine, maintient la répression transcriptionnelle de nombreux gènes du développement. L'altération de sa fonction compromet le développement embryonnaire et est fréquemment observée dans des pathologies telles que le cancer. Nous avons précédemment montré que EZHIP est un interacteur direct du complexe répressif Polycomb 2 (PRC2) et qu'il inhibe son activité enzymatique, limitant ainsi le dépôt de H3K27me3. Il est important de noter qu'EZHIP est principalement exprimé dans les gamètes et que son knock-out chez la souris entraîne une réduction de la fertilité féminine (Ragazzini et al 2019). En poursuivant l'étude du rôle d'EZHIP dans les gamètes, nous avons observé que le stock maternel d'EZHIP est important pour réguler un ensemble de gènes soumis à une empreinte transitoire dans les embryons préimplantatoires. En l'absence d'EZHIP, les deux allèles sont exprimés. Ces changements d'expression sont corrélés à des modifications importantes du dépôt global de H3K27me3. Il est important de noter que l'absence d'EZHIP a également des conséquences importantes sur l'expression des gènes liés au chromosome X. Nous présenterons notre caractérisation extensive des changements du transcriptome et des altérations de H3K27me3 qui révèlent le rôle crucial d'EZHIP comme nouveau composant maternel de la machinerie Polycomb dans le développement précoce de la sourisThe Polycomb machinery, through its chromatin regulating activities, maintains gene silencing of many developmental genes. Alteration of its function impairs embryonic development and is frequently reported in pathologies including cancer. We previously showed that EZHIP is a direct interactor of the Polycomb Repressive Complexe 2 (PRC2) and inhibits its enzymatic activity, thereby limiting H3K27me3 deposition. Importantly, EZHIP is primarily expressed in gametes and its knockout in mice result in reduced female fertility (Ragazzini et al 2019). Further investigating the role of EZHIP in gametes, we observed that the maternal pool of EZHIP is important to regulate a set of transiently imprinted genes in preimplantation embryos. In the absence of EZHIP, both parental alleles are expressed, in correlation with important changes with global H3K27me3 deposition. Importantly, absence of EZHIP has also important consequences on X linked gene expression. We will present our extensive characterization of transcriptome changes and H3K27me3 alterations which reveal the crucial role of EZHIP as a new maternal component of the Polycomb machinery in early mouse development
16
Santos, Marcos Juliano dos 1980. "A avaliação da evolução pós-operatória dos ependimomas intramedulares." [s.n.], 2013. http://repositorio.unicamp.br/jspui/handle/REPOSIP/309592.
Анотація:
Orientador: Helder TedeschiDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
Made available in DSpace on 2018-08-22T14:04:03Z (GMT). No. of bitstreams: 1 Santos_MarcosJulianodos_M.pdf: 1157265 bytes, checksum: d4e3bca14a9db06599e52397627cd980 (MD5) Previous issue date: 2013
Resumo: Os ependimomas intramedulares são tumores de crescimento lento que acarretam déficits neurológicos progressivos e pode levar os pacientes a dependência funcional. Embora a remoção microcirúrgica seja o tratamento de escolha para a lesão, questionamento existe sobre se pacientes com apenas sinais clínicos leves devem ser submetidos a ressecções cirúrgicas radicais. Este estudo avaliou, segundo a escala funcional de McCormick, a evolução pós-operatória de uma série de vinte pacientes submetidos à ressecção microcirúrgica total para ependimomas intramedulares. A ressecção completa foi atingida em 19 dos 20 pacientes (95%), somente 1 paciente apresentou piora clínica (5%). Nos pacientes com independência funcional pré-operatória, com McCormick grau I e II, não houve piora clínica e todos os tumores foram ressecados completamente. No subgrupo de pacientes grau II, a média do status funcional pós-operatória apresentou melhora estatisticamente significativa. Nenhum paciente com grau IV melhorou após o tratamento cirúrgico. O tratamento cirúrgico foi eficaz para ressecar completamente os tumores sem agregar déficits neurológicos na maioria dos pacientes. Nos pacientes com McCormick graus I e II pré-operatório a cirurgia deve ser indicada no momento do diagnóstico
Abstract: Intramedullary ependymomas are slow-growing lesions that progressively lead to neurological compromise and functional dependence. Although surgical excision is the treatment of choice for such lesions, there is questioning as to whether patients with only subtle clinical findings should be subjected to radical surgical resections. This study has evaluated according to the McCormick functional scale the surgical outcome of a series of twenty patients with intramedullary ependymomas submitted to microsurgical resection. Total surgical resection was achieved in 19 of the 20 patients (95%). Only one patient experienced clinical worsening (5%). Patients classified as McCormick grade I and II who were independent pre-operatively remained so in the post-operative period and had their tumors completely removed. In grade II patients there was a significant improvement in their post-operative status. None of the grade IV patients improved after surgical treatment. Surgical treatment has proven to be efficient in completely removing tumors without adding neurological deficits in most patients. In patients McCormick grades I and II pre-operatively surgery should be indicated early in the diagnosis
Mestrado
Neurologia
Mestre em Ciências Médicas
17
Pein, Anna von [Verfasser], and Christian [Akademischer Betreuer] Hagel. "Untersuchungen zur Expression von Nestin und Glykoprotein nmb in kindlichen Ependymomen / Anna von Pein ; Betreuer: Christian Hagel." Hamburg : Staats- und Universitätsbibliothek Hamburg, 2019. http://d-nb.info/1194547915/34.
18
Pein, Anna von Verfasser], and Christian [Akademischer Betreuer] [Hagel. "Untersuchungen zur Expression von Nestin und Glykoprotein nmb in kindlichen Ependymomen / Anna von Pein ; Betreuer: Christian Hagel." Hamburg : Staats- und Universitätsbibliothek Hamburg, 2019. http://nbn-resolving.de/urn:nbn:de:gbv:18-99531.
19
Stein, Roland Gregor [Verfasser], and Wolfgang [Akademischer Betreuer] Roggendorf. "Immunhistochemische Marker für die Prognose und Proliferation in Ependymomen bei Kindern und Erwachsenen / Roland Gregor Stein. Betreuer: Wolfgang Roggendorf." Würzburg : Universität Würzburg, 2012. http://d-nb.info/1102819956/34.
20
Kamaly-Asl, Ian. "Molecular, genetic, patient and surgical factors involved in the development and outcome of central nervous system tumours." Thesis, University of Manchester, 2011. https://www.research.manchester.ac.uk/portal/en/theses/molecular-genetic-patient-and-surgical-factors-involved-in-the-development-and-outcome-of-central-nervous-system-tumours(3e42d00e-b543-452e-bd71-ff53e194d944).html.
Анотація:
Prognostic factors come in a variety of forms and may be patient, tumour or environmental related. This thesis examines the interaction of prognostic factors for a variety of tumour types. It particularly focuses on single nucleotide polymorphisms (SNPs) of the vascular endothelial growth factor (VEGF) gene. The first section on meningiomas describes the frequency of sex steroid receptors in meningiomas. In this study, absence of progesterone receptors is associated with high tumour grade and male gender. Tumours that are progesterone receptor negative have an odds ratio for recurrence of 5.Choroid plexus carcinomas are aggressive malignant tumours generally occurring in young children. Gross total surgical resection has been shown to be a highly significant factor in tumour recurrence and survival. This study describes a treatment paradigm of neoadjuvant ICE chemotherapy in these children which decreases the vascularity and increase the chance of a complete removal. The operative blood loss with this regimen is reduced to 0.22 blood volumes from 1.11 blood volumes without neoadjuvant chemotherapy. The VEGF gene is highly polymorphic and SNPs of the region have previously been shown to influence VEGF protein expression. This study looks at cohorts of both adult gliomas and a variety of paediatric brain tumours; comparing them to controls. There are several associations described between the development of certain tumours and specific SNP genotypes. In addition to this, certain genotypes and haplotypes have an influence on survival of adult grade 2 astrocytomas and paediatric medulloblastomas and ependymomas. There are consistent themes to the prognostic genotypes throughout both the adult and the paediatric tumours.Prognostic factors come in a variety forms as described in this thesis. It is vital to understand the complex interaction between factors to best utilise them for the benefit of patients.
21
Dünschede, Jutta [Verfasser]. "Retrospektive Analyse des postoperativen Outcome zur Diskussion des therapeutischen Vorgehens unter Beleuchtung diverser neurologischer Variablen bei Patienten mit intramedullären Ependymomen / Jutta Dünschede." Tübingen : Universitätsbibliothek Tübingen, 2020. http://d-nb.info/1214640028/34.
22
Kolevatova, Larissa [Verfasser], and Markus [Akademischer Betreuer] Glatzel. "Untersuchungen zum Epidermal-growth-factor-receptor-Status in Ependymomen : Vergleich von immunhistochemischen Färbungen und Floureszenz-in-situ-Hybridisierung / Larissa Kolevatova. Betreuer: Markus Glatzel." Hamburg : Staats- und Universitätsbibliothek Hamburg, 2011. http://d-nb.info/1020427930/34.
23
Wening, Janna [Verfasser], and Stefan [Akademischer Betreuer] Rutkowski. "Auswertung des Studienzweigs E-HIT2000 – Therapie von Kindern mit Ependymom in der prospektiven multizentrischen HIT2000 Studie / Janna Wening ; Betreuer: Stefan Rutkowski." Hamburg : Staats- und Universitätsbibliothek Hamburg, 2019. http://d-nb.info/1175092010/34.
24
Wening, Janna Verfasser], and Stefan [Akademischer Betreuer] [Rutkowski. "Auswertung des Studienzweigs E-HIT2000 – Therapie von Kindern mit Ependymom in der prospektiven multizentrischen HIT2000 Studie / Janna Wening ; Betreuer: Stefan Rutkowski." Hamburg : Staats- und Universitätsbibliothek Hamburg, 2019. http://nbn-resolving.de/urn:nbn:de:gbv:18-94816.
25
Luzuric, Dominique. "Tumeurs intra-médullaires de l'enfant : aspect particulier de l'épendymome géant de la queue de cheval." Montpellier 1, 1990. http://www.theses.fr/1990MON11137.
26
De, Bustos Cecilia. "Genetic and Epigenetic Variation in the Human Genome : Analysis of Phenotypically Normal Individuals and Patients Affected with Brain Tumors." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-6629.
27
Wild, Florian [Verfasser], and Makoto [Akademischer Betreuer] Nakamura. "Die Behandlung intraspinaler Ependymome in den letzten 20 Jahren in der Klinik für Neurochirurgie der Medizinischen Hochschule Hannover : Ergebnisse von 49 Patienten / Florian Wild. Klinik für Neurochirurgie des Zentrums Neurologische Medizin Medizinische Hochschule Hannover. Betreuer: Makoto Nakamura." Hannover : Bibliothek der Medizinischen Hochschule Hannover, 2014. http://d-nb.info/1066605165/34.
28
Andrade, Fernanda Gonçalves de. "Estudo das alterações na expressão gênica dos ependimomas." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/5/5138/tde-01092014-154140/.
Анотація:
Ependimomas são tumores gliais raros. Podem ser encontrados em qualquer localização do sistema nervoso central e, apesar de histologia similar, parecem apresentar alterações genômicas distintas. As variáveis clínicas são intercorrelacionadas e, geralmente, incapazes de predizer o curso da doença. O objetivo do presente estudo foi analisar a expressão aumentada de genes e proteínas em ependimomas e correlacionar com dados clínicos dos pacientes. Foram estudados casos de pacientes com ependimoma submetidos à ressecção cirúrgica no Hospital das Clínicas, Universidade de São Paulo, no período entre 1996 e 2011 (33 amostras de tecido congelado para análise de expressão gênica por PCR quantitativo em tempo real e 149 amostras com tecido incluído em parafina, correspondentes a 121 casos devido a recidivas, para análise de proteína por imuno-histoquímica de tissue microarrays). As reações de imuno-histoquímica foram analisadas semiquantitativamente e graduadas com um índice de marcação calculado pelo produto da porcentagem de núcleos marcados pela intensidade de marcação. Oitenta e um casos eram adultos (média de 27,2 anos). Havia 60 casos intracranianos e 61 intramedulares, dos quais 10 eram mixopapilares, 92 grau II e 19 grau III. Ressecção completa foi possível em 62% dos casos e recidiva foi confirmada em 41,1%. Observou-se menor tempo para recidiva em crianças e tumores intracranianos, supratentoriais (p < 0,001 em ambos), histologia anaplásica e ressecções incompletas (p < 0,05 em ambos). Os seguintes genes foram selecionados em dados públicos de SAGE e literatura: ARMC3, CCND1, CHST5, DNALI1, FGFRL1, GNA13, IGF2, MSX1, NOTCH1 e RSPH3. ARMC3, RSHL3, CHST5 e DNALI1 apresentaram maiores níveis de expressão em ependimomas intramedulares (p < 0,05), e FGFRL1, NOTCH1 e CCND1 nos casos supratentoriais (p < 0,01). IGF2 apresentou maiores níveis de expressão em crianças e CHST5 em adultos (p < 0,05 em ambos). Foram observados maiores níveis de expressão de FGFRL1 (p < 0,05), CCND1 e IGF2 (p < 0,01 em ambos) em casos com histologia anaplásica. Nenhum dos genes analisados apresentou impacto no tempo livre de progressão ou na sobrevida. A expressão da proteína codificada por CCND1, ciclina D1, também foi avaliada por imuno-histoquímica, por ser uma proteína com expressão aumentada em diversos tipos de neoplasias e não ter ainda um valor prognóstico bem estabelecido em ependimomas. Houve correlação entre expressão de ciclina D1 a nível de mRNA e da proteína (p < 0,0001). As correlações entre ciclina D1 e histologia anaplásica e localização supratentorial foram confirmadas pela análise proteica (p < 0,0001 em ambos). Adicionalmente, foi também observada maior expressão de ciclina D1 em pacientes mais jovens (p < 0,01). A maior expressão de ciclina D1 em tumores com localização supratentorial foi independente do grau histológico e da idade do paciente. Recidiva foi mais frequente em casos com maiores níveis de expressão de ciclina D1 (p < 0,05), embora uma maior correlação com tempo livre de progressão foi observada apenas em casos com ressecção completa (p < 0,001). Os ependimomas apresentaram expressão gênica diferencial de acordo com idade, localização do tumor e grau histológico nesse estudo. A determinação dos níveis da expressão de ciclina D1 pode ser útil para guiar o seguimento e tratamento dos casos supratentoriais com ressecções completasEpendymomas are rare glial cell-derived tumors. They can be found in any central nervous system localization and despite the histological similarity, they seem to display distinct genomic abnormalities. Clinical variables are intercorrelated and they are usually unable to predict the disease course. We aimed to analyze increased gene and protein expression in ependymomas and to correlate with patients\' clinical data. We studied patients with ependymoma submitted to surgical resections at Hospital das Clinicas, University of São Paulo, from 1996 to 2011 (33 fresh-frozen samples for gene expression analysis by quantitative real-time PCR and 149 formalin-fixed, paraffin-embedded samples, relative to 121 patients due to relapses, for protein analysis by tissue microarray immunohistochemistry). Immunohistochemical reactions were analyzed semi-quantitatively and scored with a labeling index (LI) calculated as the product of the percentage of the positively stained nuclei by the intensity of staining. Eighty-one cases were adults (mean 27.2 years). There were 60 intracranial and 61 spinal cases, of which 10 tumors were myxopapillary, 92 were grade II and 19 were grade III. Gross total resection was achieved in 62% of cases and relapse was confirmed in 41.4% of cases. We observed a shorther time to relapse in children and supratentorial intracranial tumor localization (p<0.001 for both), anaplastic histology and incomplete resections (p<0.05 for both). The following genes were selected based on public SAGE database and literature: ARMC3, CCND1, CHST5, DNALI1, FGFRL1, GNA13, IGF2, MSX1, NOTCH1 and RSPH3. ARMC3, RSHL3, CHST5 and DNALI1 presented higher expression levels in intramedullary ependymomas (p < 0.05) and FGFRL1, NOTCH1 and CCND1 in supratentorial cases (p < 0.01). IGF2 presented higher expression levels in pediatric cases and CHST5 in adults cases (p < 0.05 in both). Higher expression levels of FGFRLI1 (p < 0.05), CCND1 and IGF2 (p < 0.01 for both) were observed in anaplastic histology cases. None of the genes impacted in progression free survival or overall survival of patients. The expression of protein codified by CCND1, cyclin D1, was also evaluated by immunohistochemistry, because its overexpression has been related with several types of neoplasias and its prognostic value has not yet been fully established in ependymomas. There was a correlation of cyclin D1 expression at mRNA and protein levels (p < 0.0001). Correlations between cyclin D1 and anaplastic histology and supratentorial localization were confirmed by protein analyses (p < 0.0001 for both parameters). Additionally, high expression of cyclin D1 was observed in younger patients (p < 0.01). The higher cyclin D1 expression in supratentorial tumor localization was independent of histological grade and age of patient. Relapse was more frequent in cases with higher cyclin D1 expression levels (p < 0.05) although correlation with progression free survival was just observed in gross total resection cases (p < 0.001). Ependymomas presented differential gene expression according to age, tumor localization and histological grade in our study. Determination of cyclin D1 expression levels may be useful to guide follow-up and treatment in supratentorial cases with gross total resection
29
Liang, Muh-Lii, and 梁慕理. "The Mechanism of MicroRNAs/mRNAs Interactomes in Pediatric High-grade Gliomas and Radio-resistance in Pediatric Ependymomas." Thesis, 2018. http://ndltd.ncl.edu.tw/handle/5vpjng.
Анотація:
博士國立陽明大學
臨床醫學研究所
106
High-grade gliomas and ependymomas are two main challenging malignancies in children, and which composed of a majority of central nervous system (CNS) tumors of young patients. In addition to maximal safe surgical resection and limited efficacy of chemotherapy, the applications of adjuvant irradiation play an important role for the tumor treatment. However, in the young ages, the resistance of residual and recurrent tumor, and long-term intellectual sequelae remain the major obstacles of radiotherapy. The advancement of high-throughput next-generation sequencing and molecular clustering technologies largely promoted the study of neuro-oncology from diagnosis based molecular to therapeutic targets in the last decade. In order to identify potential targets for the development of new therapeutic strategies, we compared the miRNome and transcriptome of pediatric low- (pLGGs) and high-grade gliomas (pHGGs) using small RNA sequencing (smRNA-Seq) and gene expression microarray, respectively in the first study. Through integrated bioinformatics analyses and experimental validation, we identified miR-137 and miR-6500-3p are significantly downregulated in pHGGs. Overexpression of miR-137 or miR-6500-3p reduced cell proliferation in two pHGG cell lines, SF188 and UW479. We also identified mRNA/miRNA interactions and confirmed that CENPE, KIF14 and NCAPG levels were direct targets of miR-137 or miR-6500-3p and were significantly higher in pHGGs than pLGGs. Furthermore, knockdown of CENPE, KIF14 or NCAPG combined with temozolomide treatment resulted in a combined suppressive effect on pHGG cell proliferation. These targets combined with chemotherapy are also potential therapeutic strategy. In the secondary study, we focused on the mechanism of therapeutic failure caused by radio-resistance and identified the significance of cyclin D1 overexpression in progression and radio-resistance of pediatric ependymomas. Here we analyze clinic-pathological factors in 82 cases of ependymoma less than 20 years old and 31 out of 82 (37.8%) patients are under 3-year-old. The 10 years PFS and OS are 38% and 60%. Gross-total resection is the single significant prognostic factor for longer 10 years progression free survival (PFS) and overall survival (OS) in the multi-variant analysis (p<0.05). We demonstrated that 24 primary (92%) and 16 recurrent (95%) ependymomas were up-regulated, and 5 out of 7 paired samples exhibited higher CCND1 expression in recurrent tumors. Knocking down CCND1 reduced cell proliferation and repressed genes associated with S-phase and DNA repair. Homologous recombination activities of DNA repair were significantly decreased in CCND1-deficient cells while the level of H2AX was increased after irradiation. We treated ependymoma cells with palbociclib plus irradiation significantly suppressed expression of CDC6, MCM2, MAD2L1, CDK2, BRCA2 and RAD51 genes, and induced higher H2AX level after 24 hours and also reduced cell proliferation. In summary, our findings identify novel mRNA/miRNA interactions in pediatric high-grade gliomas and also suggest a robust role of CCND1 in regulating cell proliferation and radio-resistance in ependymomas, which providing insight of mechanism related to the radio-resistance and the potential therapeutic targets for both pediatric high-grade gliomas and ependymomas.
30
Gentner, Doreen. "Chromosom 9 in Ependymomen - Eine Mikrosatellitenanalyse." Doctoral thesis, 2010. https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-55975.
Анотація:
Basierend auf die vorangegangene Studie der Abteilung für Neuropathologie des Pathologischen Instituts der Universität Würzburg, in der genetische Aberrationen auf dem Chromosom 9 in Ependymome beschrieben wurden, sollte eine Screeninguntersuchung des gesamten Chromosoms sowie eine verfeinerte Analyse der zuvor auffälligen Regionen erfolgen. Ziel der vorliegenden Arbeit war es, mögliche Tumorsuppressorgene oder Onkogene, die mit der Entstehung oder Progression von Ependymome verbunden sind, zu definieren. Weiterhin sollte eine Korrelation zu den klinischen Daten erfolgen. Dabei konnte bei erwachsenen Patienten gezeigt werden, dass Aberrationen auf Chromosom 9 die Prognose verbessern. Speziell der Marker D9S1872 bei DCR1 (DBCCR1) zeigte einen Trend zu einem Überlebensvorteil bei Erwachsenen. Deshalb könnte er in Zukunft zur prognostischen Einteilung von Ependymompatienten in der Klinik beitragen. Des Weiteren konnten bei Kindern in supratentoriellen Tumoren signifikant mehr Aberrationen gefunden wurden als in infratentoriellen. Dies deutet darauf hin, dass Ependymome zumindest bei Kindern abhängig von der Lokalisation unterschiedliche Entstehungswege haben. Es konnten zwei Regionen identifiziert werden, in denen sich häufig Aberrationen fanden: 9p21.1-22.3 und 9q31.3-33.3. Weiterhin konnten Lokalisation und Resektionsausmaß als unabhängige Prognosefaktoren bestätigt werdenBased on a former study of the departmentof neuropathology of the pathologic instisute of the university of Wuerzburg, in which aberrations on chromosome 9 in ependymomas had been described, the whole chromosome should be screened and a finer analysis of previously aberrated regions should be carried out. The aim of the thesis was defining possible tumor suppressor genes or oncogenes being involved in the development and progression of ependymomas. Moreover there should be a correlation to the clinical data. Adults with ependymomas harboring aberrations on chromosome 9 showed significantly longer overall survival than patients of the same group without this aberration, irrespective of the extent of resection in multivariate analysis. Aberrations of chromosome 9, and particularly of DCR1 (DBCCR1), may play a role in the prognostic evaluation for ependymomas in adults in the future. In pediatric patients, genetic aberrations were found significantly more often in supratentorial tumors than in tumors with infratentorial location. Two common regions of deletions were identified (9p21.1 approximately p22.3 and 9q31.3 approximately q33.2). Localization and extend of resection could be confirmed as prognostic factors
31
"Combining CGH and high-resolution allelotyping study for ependymoma." 2001. http://library.cuhk.edu.hk/record=b5890889.
Анотація:
Zheng Ping-pin.Thesis submitted in: December 2001.
Thesis (M.Phil.)--Chinese University of Hong Kong, 2001.
Includes bibliographical references (leaves 118-159).
Abstracts in English and Chinese.
ACKNOWLEDGEMENTS --- p.i
ABSTRACT(ENGLISH/CHINESE) --- p.iii
CONTENTS --- p.viii
LIST OF TABLES --- p.xi
LIST OF FIGURES --- p.xii
PUBLICATION --- p.xiii
Chapter CHAPTER I --- INTRODUCTION
Chapter I.1. --- Preface --- p.1
Chapter I.2. --- Overview of Carcinogenesis --- p.2
Chapter I.3. --- Oncogene --- p.5
Chapter I.4. --- Tumor Suppressor Genes (TSGs) --- p.6
Chapter I.5 --- Detection of Oncogene and Tumor Suppressor Genes --- p.9
Chapter I.5.1 --- Detaction of Oncogene --- p.9
Chapter I.5.2. --- Detection of Tumor Suppressor Genes --- p.11
Chapter I.6. --- Profiles of Oncogenes/TSGs and Molecular Subtype about Astrocytic Tumors --- p.17
Chapter I.7. --- Intratumoral Heterogeneity and Microsatellite Instability --- p.20
Chapter I.8. --- Outline of Ependymoma --- p.20
Chapter I.9. --- Clinicopathological Factors and Prognosis --- p.22
Chapter I.9.1. --- Histology and Grading (2000) --- p.22
Chapter I.9.2. --- Prognosis Factors --- p.23
Chapter I.9.2.1. --- Age/Sex/Location --- p.23
Chapter I.9.2.2. --- Extent of Resection --- p.25
Chapter I.9.2.3. --- Radiotherapy and Chemotherapy --- p.25
Chapter I.9.2.4. --- Histology --- p.26
Chapter I.10. --- "Cytogenetic, Molecular Genetic and Molecular Studies" --- p.27
Chapter I.11. --- Advantages and Disadvantages of The Research Methods --- p.34
Chapter CHAPTER II --- AIM OF STUDY --- p.36
Chapter CHAPTER III --- MATERIALS AND METHODS --- p.37
Chapter III.1. --- Tumor Samples and DNA Preparations --- p.37
Chapter III.1.1. --- Tumor Samples --- p.38
Chapter III.1.2. --- DNA Preparation --- p.38
Chapter III.2. --- Comparative Genomic Hybridization --- p.42
Chapter III.2.1. --- Metaphase Preparation --- p.42
Chapter III.2.2. --- "DNA Labeling, Hybridization, and Detection" --- p.43
Chapter III.2.3. --- Digital Image Analysis --- p.45
Chapter III.3 --- High-Resolution Allelotying (Microsatellite Analysis) --- p.46
Chapter III.3.1 --- General Outline --- p.46
Chapter III.3.2 --- Multiplex PCR --- p.47
Chapter III.3.3 --- Pooling of PCR Products --- p.49
Chapter III.3.4 --- Electrophoresis --- p.50
Chapter III.3.5. --- Assessment of Allelic Imbalance by Calculating Allelic Ratio --- p.52
Chapter III.3.6 --- Standards of Evalution --- p.53
Chapter III.3.7 --- Separating Allelic Loss from Allelic Duplication --- p.54
Chapter III.3.8 --- Statistical Analyses --- p.54
Chapter CHAPTER IV --- RESULTS --- p.54
Chapter IV.1. --- CGH Study --- p.54
Chapter IV.1.1 --- Overview --- p.54
Chapter IV.1.2 --- Common Deletion Regions --- p.58
Chapter IV.1.3 --- Common duplication Regions --- p.60
Chapter IV.2. --- High-Resolution Allelotyping (Microsatellite Analysis) --- p.60
Chapter IV.2.1. --- Overview of Results --- p.60
Chapter IV.2.2. --- LOH profile of Individual Chromosome --- p.93
Chapter IV.2.3. --- Overlapping Small Deletion Regions --- p.95
Chapter CHAPTER V --- DISCUSSION --- p.97
Chapter V.1. --- . General Outline --- p.98
Chapter V.2. --- Chromosome 22 --- p.99
Chapter V.3. --- Chromosome 17 --- p.102
Chapter V.4. --- Chromosome 6 --- p.104
Chapter V.5. --- Chromosome 16 --- p.105
Chapter V.6. --- Chromosome 19 --- p.107
Chapter V.7. --- Chromosome 20 --- p.108
Chapter V.8. --- Chromosome 7 --- p.109
Chapter V.9. --- Chromosome 12 --- p.110
Chapter V.10. --- Chromosome 9 --- p.111
Chapter V.11. --- Chromosome 5 --- p.112
Chapter V.12. --- Chromosome 4 --- p.112
Chapter V.13. --- Correlation of CGH with Allelotyping in the Study --- p.112
Chapter V.14. --- Conclusion --- p.114
Chapter CHAPTER VI --- LIMITATIONS OF THE STUDY --- p.115
Chapter CHAPTER VII --- FUTURE STUDY --- p.116
REFERENCES --- p.118
32
Eicker, Monika [Verfasser]. "Monosomie 22 in Ependymomen / vorgelegt von Monika Eicker." 2006. http://d-nb.info/995894825/34.
33
Barszczyk, Mark. "Telomerase as a Prognostic Marker and Therapeutic Target in Paediatric Ependymoma." Thesis, 2013. http://hdl.handle.net/1807/42680.
Анотація:
Paediatric ependymomas are the third most common childhood brain cancer and represent a prognostic and therapeutic challenge. Previous evidence suggests that telomerase, a ribonucleoprotein critical in permitting limitless growth potential, may serve as both a prognostic marker and therapeutic target. Immunohistochemical analysis (n=198) and enzymatic detection (n=25) of telomerase was performed to determine prevalence and prognostic potential. The telomerase inhibitor Imetelstat was used to study telomerase inhibition in paediatric ependymoma cell lines, tumour initiating cells (TICs) and both subcutaneous and intracranial xenografts. Telomerase activity was detected in 76% of primary ependymomas and was associated with a reduced five-year progression-free survival (30% vs 75%). Telomerase inhibition in vitro resulted in shortened telomeres, increased senescence, growth inhibition and reduced self-renewal capacity. In vivo, Imetelstat shortened telomeres and reduced subcutaneous tumour volume by 40% compared to control mice. Therefore, telomerase may serve as an ideal prognostic marker and therapeutic target in paediatric ependymoma.
34
Gentner, Doreen [Verfasser]. "Chromosom 9 in Ependymomen : eine Mikrosatellitenanalyse / vorgelegt von Doreen Gentner." 2010. http://d-nb.info/1011275961/34.
35
Heinemann, Uta [Verfasser]. "Molekulargenetische Veränderungen auf Chromosom 22 in Ependymomen / vorgelegt von Uta Heinemann." 2008. http://d-nb.info/987363387/34.
36
Stein, Roland Gregor. "Immunhistochemische Marker für die Prognose und Proliferation in Ependymomen bei Kindern und Erwachsenen." Doctoral thesis, 2012. https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-71082.
Анотація:
Zur Identifizierung geeigneter Routinemarker für die Prognose von Ependymompatienten führten wir immunhistochemische Untersuchungen und statistische Auswertungen an Ependymomen und Daten von 32 Erwachsenen und 23 pädiatrischen Patienten durch. Davon wurden bei drei Tumoren auch Rezidive untersucht, so dass insgesamt 59 Ependymome in die Untersuchung eingeschlossen wurden. Im Einzelnen handelte es sich um 11 myxopapilläre Ependymome, 6 Subependymome, 19 Ependymome und 23 anaplastische Ependymome. Die größten Fallgruppen bildeten pädiatrische Patienten unter drei Jahren und Erwachsene zwischen 50 und 70 Jahren. Bei Kindern war mit 45,8% die infratentorielle, bei Erwachsenen mit 65% die spinale Tumorlokalisation am häufigsten. Die untersuchten spinalen Ependymome entsprachen zu gleichen Teilen myxopapillären Ependymomen WHO Grad I und Ependymomen WHO Grad II. In supratentorieller Lage fanden sich mit 67% überwiegend anaplastische Ependymome WHO Grad III. Auch bei den infratentoriell gelegenen Ependymomen waren mit 63% die Mehrzahl anaplastische Ependymome, daneben fanden sich 29,6% Ependymome WHO Grad II. Beim Vergleich des von uns definierten und bestimmten Ki67-Scores als Zeichen für die Ependymomproliferation und der immunhistochemischen Positivität für HCK fiel nach Anwendung des Chi-Quadrat-Tests mit p=0,067 ein deutlicher Trend zu schwächerer punktförmiger Positivität bei höherem Ki67-Score auf. Dieser Trend setzte sich in der Erwachsenengruppe separat fort, während er in der Kindergruppe allein nicht nachweisbar war. In der Erwachsenengruppe war mit 28% ein deutlicher Anteil myxopapillärer Ependymome vorhanden, welche bei den Kindern nur 8% ausmachten.Möglicherweise spielt die veränderte HCK-Expression in der Subgruppe der myxopapillären Ependymome eine Rolle. Unsere Untersuchungen zeigten außerdem mit p=0,057 einen deutlichen Trend zu längerem Überleben bei immunohistochemischer DBC1-Negativität. Die Multivarianzanalyse mittels Cox-Regression wies eine Positivität für DBC1 als unabhängigen Risikofaktor für eine kürzere Überlebenszeit nach. Des Weiteren konnte eine mit p=0,013 signifikante Korrelation zwischen immunhistochemischer Positivität für DBC1 und höherem Ki67-Score gezeigt werden. Auch mit höherem WHO-Grad korrelierte die DBC1-Positivität mit p=0,009. Besonders infratentoriell gelegene Ependymome zeigten DBC1-Reaktivität. Hier treten bekannterweise häufiger anaplastische Ependymome mit höherem Proliferationsindex auf. Unsere Ergebnisse legen somit die Eignung des Markers DBC1 als immunhistochemische Routineuntersuchung für die Beurteilung der vom Resektionsstatus unabhängigen Prognose und Überlebenszeit von Ependymompatienten naheImmunohistochemical markers for prognosis and proliferation in ependymomas of children and adults
37
Stettner, Georg Martin. "Immunhistologische und morphometrische Untersuchung der Ependymome im Kindesalter in Korrelation zu den klinischen Befunden." Doctoral thesis, 2003. https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-6932.
Анотація:
In der vorliegenden Arbeit wurden der klinische Verlauf der Tumorerkrankung von 40 Kindern, die an einem Ependymom erkrankten, erfasst und 58 Tumorproben mittels immunhistochemischer Methoden untersucht. Im Mittelpunkt dieser Untersuchungen standen die Überprüfung der p53-Akkumulation, der Proliferationsaktivität mit Hilfe des Antikörpers MIB-1 sowie der Expression von HLA-DR durch Tumorzellen und eine Einschätzung der prognostischen Aussagekraft dieser Faktoren. Weiterhin wurde die EMA-Expression untersucht und eine Schwerpunkt auf die Analyse von Verteilung und Proliferationsaktivität der Zellen des Mikroglia(MG)/Makrophagen-Systems in kindlichen Ependymomen gelegt. Das mittlere Alter bei Diagnosestellung lag bei 61 Monaten (8 Monate bis 15 4/12 Jahre, Median: 41 Monate), eine Geschlechtspräferenz lag nicht vor. 22,5% der Primärtumoren waren supratentoriell, 60% infratentoriell und 17,5% spinal lokalisiert. 52,5% der Primärtumoren waren anaplastische Ependymome (WHO Grad III), 40% Ependymome (WHO Grad II), 7,5% myxopapilläre Ependymome (WHO Grad I). Eine totale Resektion konnte in 30,8% bei Primärtumoren und in 27,3% bei Rezidivtumoren erzielt werden. Das mittlere Nachbeochtungsintervall betrug 52 Monate (6-163 Monate), das mittlere progrssionsfreie Interval (PFS) 28 Monate und der mittlere Überlebenszeitraum (OS) 64 Monate. Tumorrezidive entwickelten sich mit einer Ausnahme eines Spätrezidives nach 84 Monaten innerhalb von 36 Monaten nach der operativen Tumorentfernung. Von den klinischen Variablen weist einzig das Resektionsausmaß eine prognostische Bedeutung auf (total vs. inkomplett: p=0.035 bezüglich des mittleren PFS, p=0.12 bezüglich des mittleren OS). Alle anderen klinischen Variablen, einschließlich des Tumorgrades nach WHO, zeigen keinen Einfluss auf den Verlauf der Tumorerkrankung. p53-Akkumulation kommt in 56,9% der untersuchten Tumorproben vor und korreliert mit dem Tumorgrad nach WHO, dem MIB-1 Labeling Index (LI) und der Lokalisation. Der MIB-1 LI zeigt eine große Streubreite (1,4% - 63,3%) und weist entsprechend des untersuchten Patientenkollektivs im Gegensatz zu Ependymomen des Erwachsenenalters einen hohen Mittelwert und Median auf (21,8% bzw. 19,8%). Der MIB-1 LI korreliert statistisch signifikant mit dem WHO-Graduierungssystem, der Lokalisation und wie bereits erwähnt mit der p53-Akkumulation. Unter den immunhistochemisch untersuchten Variablen kommt lediglich dem MIB-1 LI im untersuchten Patientenkollektiv eine gewisse prognostische Aussagekraft zu. Statistische Signifikanz wird allerdings nicht erreicht (MIB-1 LI <10% vs. MIB-1 LI >10%: p=0.17 bezüglich des mittleres PFS). Erstmals wurde in 80,4% der untersuchten ependymalen Tumoren auch eine Proliferation von Zellen des MG/Makrophagen-Systems nachgewiesen. Bei weitgehend konstant niedriger absoluter Anzahl proliferierender Zellen des MG/Makrophagen-Systems existiert kein Unterschied diesbezüglich zwischen den Tumorgraden wie kürzlich bei astrozytären Tumoren nachgewiesen. Die Verteilung der Zellen des MG/Makrophagen-Systems zeigte bei sehr heterogenem Verteilungsmuster häufig eine septale Anordnung insbesondere der amöboiden MG und der Makrophagen. Es existieren unterschiedliche Verteilungsmuster mikroglialer Zellen und Makrophagen, die sich aber anderen Parametern nicht zuordnen lassen mit der Ausnahme der MG/Makrophagen-Zelldichte in Primärtumoren. Obwohl eine HLA-DR Expression durch Tumorzellen auch in anderen Neoplasien des ZNS häufig vorkommt, wurden Ependymome diesbezüglich bisher nicht untersucht. In 52,6% aller Tumorproben finden sich in der vorliegenden Arbeit HLA-DR exprimierende Tumorzellen. Eine EMA-Expression zeigt sich in 84,5% der untersuchten Fälle und ist damit ein Charakteristikum ependymaler Neoplasien, das auch als differentialdiagnostisches Kriterium angesehen werden kann. Die Ergebnisse der vorliegenden Arbeit bekräftigen den hohen prognostischen Stellenwert einer totalen Resektion in der Therapie ependymaler Tumoren des Kindesalters. Weiterhin wird die Bedeutung der Proliferationsaktivität für den klinischen Verlauf der Tumorerkrankung unterstrichen. Von großem wissenschaftlichem Interesse ist weiterhin die Klärung der Ursache und Bedeutung der häufig anzutreffenden p53-Akkumulation sowie der immunologischen Bedeutung der Zellen des MG/Makrophagen-Systems im Rahmen der TumorabwehrIn this dissertation the tumor’s clinical course of 40 children, who developed an ependymoma, was observed and 58 tumor samples were investigated by immunohistochemical methods. p53-accumulation, proliferation (detected by the antibody MIB-1) as well as the expression of HLA-DR by tumor cells and the prognostic value of these factors had been the focus of interest. Furthermore the EMA-expression and the distribution and proliferative activity of cells belonging to the microglia(MG)/macrophage-system in childhood ependymomas was investigated. The mean age at the time of diagnosis was 61 months (8 months to 15 4/12 years, median 41 months), the male/female ratio was balanced. 22,5% of primary tumors were located supratentorial, 60% infratentorial and 17,5% spinal. 52,5% of primary tumors were anaplastic ependymomas (WHO grade III), 40% ependymomas (WHO grade II) and 7,5% myxopapillary ependymomas (WHO grade I). A total resection was achieved in 30,8% of the primary tumors and in 27,3% of recurrent tumors. The mean follow-up was 52 months (6-163 months), the median progression free survival (PFS) and the overall survival (OS) 28 and 64 months respectively. All recurrences developed within 36 months after surgery with one exception, where a recurrence occurred after 84 months. Out of the clinical parameters a prognostic value was only seen in the extent of resection (total vs. subtotal resection: p=0.035 related to the median PFS and p=0.12 related to the median OS respectively). None of the other clinical parameters including tumor grade was correlated to the course of the disease. p53-accumulation was shown in 56,9% and there were correlations with WHO-tumor grade, MIB-1 labeling index (LI) and tumor localization. There was a wide range in MIB-1 LI (1,4% - 63,3%) with a higher mean and median (21,8% and 19,8% respectively) as reported in investigations in ependymomas of adults. There were significant correlations of MIB-1 LI with WHO-tumor grade, tumor localization and p53-accumulation as above mentioned. Out of the immunohistochemical investigated factors in this study only the MIB-1 LI was of prognostic relevance, but without statistical significance (MIB-1 LI <10% vs. MIB-1 LI >10%: p=0.17 related to the median PFS). None of the other immunohistochemical investigated factors mentioned below was related to the outcome in this study. For the first time proliferation of cells belonging to the MG/macrophage-system was documented in 80,4% of ependymal neoplasm. But there was no difference between different tumor grades in relative or absolute counts of proliferating microglial cells as previously shown in astrocytic tumors. The distribution of cells belonging to the MG/macrophage-system show a very heterogeneous pattern with a likely septal arrangement of ameboid microglia and macrophages in particular. Different distribution pattern of subgroups of the microglial cells and macrophages exist, but there is no relation to other variables except the density of microglial cells and macrophages in primary tumors. Although the HLA-DR expression in CNS neoplasms is a well known phenomenon, this is the first report of HLA-DR expression in ependymomas in 52,6% of all tumor samples. As a characteristic of ependymal neoplasms an EMA-expression was detected in 84,5%. EMA-expression can therefore be used as a criteria in differential diagnosis. The results of this study confirm the prognostic importance of a total resection of childhood ependymomas. Furthermore the relevance of proliferative activity related to the clinical course was emphasized. Further studies are needed to explain the reason and meaning of p53-accumulation and to define the role of the MG/microphage-system in the immunological tumor defense
38
"Molecular genetic studies of oligodendroglial and ependymal tumors." 1998. http://library.cuhk.edu.hk/record=b5889797.
Анотація:
by Tong Yuen Kwan.Thesis (M.Phil.)--Chinese University of Hong Kong, 1998.
Includes bibliographical references (leaves 124-141).
Abstract also in Chinese.
acknowledgements --- p.i
Abstract (English/Chinese) --- p.ii
contents --- p.vi
list of tables --- p.viii
ost of figures --- p.x
Chapter I. --- introduction --- p.1
Chapter I.1. --- Tumors of the Central Nervous System --- p.1
Chapter I.2. --- Histopathological Classification of Human Glial Tumors --- p.3
Chapter I.2.1. --- Histopathology of Astrocytic Gliomas --- p.3
Chapter I.2.1.1. --- Diffuse Astrocytomas --- p.3
Chapter I.2.1.2. --- Others --- p.6
Chapter I.2.2. --- Histopathology of Non-Astrocytic Gliomas --- p.6
Chapter I.2.2.1. --- Oligodendroglial Tumors --- p.6
Chapter I.2.2.2. --- Ependymal Tumors --- p.9
Chapter I.3. --- Tumor Suppressor Genes --- p.14
Chapter I.3.1. --- p53 --- p.14
Chapter I.3.1.1. --- Historical Perspectives --- p.14
Chapter I.3.1.2. --- Structure of p53 Gene and Protein --- p.15
Chapter I.3.1.3. --- Functions of Wild-Type p53 Protein --- p.18
Chapter I.3.1.4. --- Regulation and Modulation of the Functions of p53 --- p.21
Chapter I.3.1.5. --- Mechnism of p53 Inactivation --- p.23
Chapter I.3.1.6. --- p53 Mutation Profiles in Human Tumors --- p.25
Chapter I.3.2. --- Novel Genes --- p.28
Chapter I.3.2.1. --- PTEN/MMAC1 --- p.28
Chapter I.3.2.2. --- DMBT1 --- p.31
Chapter I.4. --- Cytogenetic and Molecular Genetic Studies in Gliomas --- p.34
Chapter I.4.1. --- Astrocytic Gliomas --- p.34
Chapter I.4.2. --- Non-Astrocytic Gliomas --- p.39
Chapter I.4.2.1. --- Oligodendroglial Tumors --- p.39
Chapter I.4.2.2. --- Ependymal Tumors --- p.46
Chapter II. --- objectives of study --- p.49
Chapter III. --- materials and methods --- p.52
Chapter III.l. --- Patients and Materials --- p.52
Chapter III.2. --- Collection of Samples --- p.57
Chapter III.3. --- DNA Extraction --- p.58
Chapter III.3.1. --- Extraction of Genomic DNA from Formalin-Fixed Paraffin Embedded Tissues --- p.58
Chapter III.3.2. --- Extraction of Genomic DNA from Blood --- p.60
Chapter III.4. --- Loss of Heterozygosity (LOH) Analysis on Chromosome 10q --- p.61
Chapter III.4.1. --- Microsatellite Markers --- p.62
Chapter III.4.2. --- Amplification of Target Sequences by PCR --- p.63
Chapter III.4.3. --- Denaturing Polyaerylamide Gel Electrophoresis --- p.64
Chapter III.4.4. --- Detection of Loss of Heterozygosity (LOH) --- p.64
Chapter III.5. --- Mutational Analysis of p53 and PTEN/MMAC1 --- p.66
Chapter III.5.1. --- Polymerase Chain Reaction-Single Strand Conformation Polymorphism (PCR-SSCP) Analysis --- p.66
Chapter III.5.1.1. --- PCR Primers --- p.66
Chapter III.5.1.2. --- PCR Amplification of Target Sequences --- p.68
Chapter III.5.1.3. --- Non-denaturing Polyacrylamide Gel Electrophoresis --- p.71
Chapter III.5.2. --- Direct DNA Sequencing Analysis --- p.72
Chapter III.5.2.1. --- Cycle Sequencing --- p.72
Chapter III.5.2.2. --- Denaturing Gel Electrophoresis --- p.73
Chapter III.6. --- Differential PCR for Detection of MDM2 Amplification --- p.74
Chapter III.6.1. --- DNA Amplification by PCR --- p.74
Chapter III.6.2. --- Polyacrylamide Gel Electrophoresis --- p.75
Chapter III.6.3. --- Detection of Gene Amplification --- p.75
Chapter IV. --- Results --- p.77
Chapter IV.1. --- LOH Analysis of Chromosome l0q --- p.77
Chapter IV.2. --- Mutational Analysis ofp53 and PTEN/MMAC1 --- p.92
Chapter IV.3. --- Differential PCR Analysis of MDM2 Amplification --- p.103
Chapter V. --- discussion --- p.109
Chapter V.l. --- p53 Gene Inactivation Studies --- p.110
Chapter V.2. --- Molecular Genetic Studies on Chromosome l0q --- p.113
Chapter V.3. --- Microsatellite Instability in Non-Astrocytic Gliomas --- p.117
Chapter V.4. --- Significance of This Study --- p.118
Chapter V.5. --- Limitations of This Study --- p.119
Chapter V.6. --- Future Studies --- p.122
Chapter VI. --- REFERENCES --- p.124
39
Michalowski, Mariana. "ETUDE DES ALTÉRATIONS EPIGENETIQUES DES TUMEURS DESENFANTS : LE CAS DES ÉPENDYMOMES ET DES NEUROBLASTOMES." Phd thesis, 2006. http://tel.archives-ouvertes.fr/tel-00115184.
Анотація:
Au cours des dernières années, un nouveau mécanisme du développement tumoral a été décrit;l'hyperméthylation des gènes suppresseurs de tumeur (GST). Les modifications « épigénétiques » ont été peu étudiées dans les cancers de l'enfant et aucune grande série de tumeurs pédiatriques existait avant 2002. Nous avons recherché ce type altérations dans deux groupes de tumeurs de l'enfant: les ependymomes et les neuroblastomes. Les ependymomes (EP) représentent la troisième tumeur la plus fréquente du système nerveux central (SNC) de l'enfant et n'a pas de marqueurs biologiques pronostiques identifiés. Le neuroblastome, quant à lui, est la tumeur solide extra crânienne la plus fréquente chez l'enfant et présente des anomalies génétiques et moléculaires qui ont été clairement liées au pronostic. Nos objectifs étaient de décrire un profil de méthylation de ces deux cancers de l'enfant et chercher des relations possibles avec l'évolution clinique. Dans la première étude, une série de 27 enfants avec un EP intracrânien et 7 avec papillome du plexus choroïde a été étudiée. Nous avons décrit et comparé le statut de méthylation de 19 gènes. Dans la deuxième étude, 62 neuroblastomes (NB) ont été évalués pour le statut de la méthylation de ces gènes. Nous n'avons pas trouvé de relation statistiquement significative entre la méthylation et l'évolution clinique, mais les méthylations ne semblent pas être distribuées sous une forme aléatoire dans les EP et les NB et peut représenter un mécanisme de développement et d'évolution tumorale. L'hyperméthylation a été corrélée au stade clinique des NB: stades 1, 2 et 4s étaient moins fréquemment méthylés que les stades 3 et 4 (p = 0.002). En conclusion, les résultats de nos séries indiquent que la méthylation des gènes suppresseurs peut avoir un rôle dans l'évolution et le développement des cancers de l'enfant.
L'étude des altérations épigénétiques est nécessaire pour améliorer la comprehension des mécanismes de la carcinogenèse dans les tumeurs pédiatriques. Ces altérations pourraient, donc, être utilisées comme des marqueurs de maladies ou d'évolutivité et les gènes méthylés pourraient être considérés comme des nouvelles cibles thérapeutiques.
40
Stein, Anne-Katrin [Verfasser]. "Evaluation von Antikörpern gegen ependymale Proteine auf ihre Eignung als diagnostische Marker für Ependymome / vorgelegt von Anne-Katrin Stein." 2009. http://d-nb.info/993332218/34.
41
Stettner, Georg Martin [Verfasser]. "Immunhistologische und morphometrische Untersuchung der Ependymome im Kindesalter in Korrelation zu den klinischen Befunden / vorgelegt von Georg Martin Stettner." 2003. http://d-nb.info/96919823X/34.
42
Pal, Jagriti. "Elucidating Deregulated Novel Pathways in Glioma through Genetic and Epigenetic Approaches." Thesis, 2016. http://etd.iisc.ac.in/handle/2005/4284.
Анотація:
Malignancy of glial cells is termed as glioma. Gliomas comprise of thirty percent of
all tumors of the central nervous system (CNS) and eighty percent of malignant brain tumors
(Goodenberger and Jenkins, 2012). Astrocytoma, a type of glioma that arise from astrocytes,
is the most common and lethal type of intracranial tumor. It is divided into four groups
according to WHO (2007) classification based on histopathology. Grade I or pilocytic
astrocytoma is benign in nature; however, the other three grades are progressively more
malignant. Grade II or diffused astrocytoma is less aggressive and have a median survival of
5-8 years (Tove et al., 2012); while Grade III or anaplastic astrocytoma and glioblastoma
(GBM) are classified under high grade gliomas with median survival of 2-3 years and 12-15
months respectively (Nuño et al., 2013; Arvold et al., 2014). GBM tumor is fast growing,
highly infiltrative, and treatment refractory. It can be divided into two categories on the basis
of their origin - primary GBM that accounts for 90 percent of GBM cases, manifest de novo
without prior evidence of a pre-existing tumor of lower grade; while secondary GBMs
develop through malignant progression of lower grade astrocytomas. Secondary GBMs
typically exhibit genetic aberrations like TP53 mutation, IDH1 mutation, PTEN mutation,
loss of chromosomal arm 10q etc. Primary GBMs show a whole host of genetic aberrations
including EGFR amplification, PDGFR amplification, mutation in TP53, PTEN, NF1, RB
etc., amplification of MDM2 and MDM4, loss of chromosomal arms 10p and 10q, CDKN2A
and CDKN2B loss (Furnari et al., 2007). With the current treatment modality of GBM that
includes surgical resection followed by radiotherapy and temozolomide chemotherapy, the
median survival achieved till date is only 15 months and in almost all cases, the tumor recurs
(Stupp et al., 2009). The aggressive and recurrent nature of GBM demands further insights
into the molecular pathways deregulated in GBM. The changes that happen within a cell that
lead to malignancy include both genetic and epigenetic alterations. Our objective is to
delineate deregulated pathways in GBM progression and development through screening of
genes via next generation sequencing (NGS) and methylome array. We further strive to
characterize the importance of identified altered molecules and deregulated pathways in the
context of GBM pathogenesis.