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Qureshi, Hammad A. "Meningioma classification using an adaptive discriminant wavelet packet transform." Thesis, University of Warwick, 2009. http://wrap.warwick.ac.uk/2790/.
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Meningioma subtypes classification is a real world problem from the domain of histological image analysis that requires new methods for its resolution. Computerised histopathology presents a whole new set of problems and introduces new challenges in image classification. High intra-class variation and low inter-class differences in textures is often an issue in histological image analysis problems such as Meningioma subtypes classification. In this thesis, we present an adaptive wavelets based technique that adapts to the variation in the texture of meningioma samples and provides high classification accuracy results. The technique provides a mechanism for attaining an image representation consisting of various spatial frequency resolutions that represent the image and are referred to as subbands. Each subband provides different information pertaining to the texture in the image sample. Our novel method, the Adaptive Discriminant Wavelet Packet Transform (ADWPT), provides a means for selecting the most useful subbands and hence, achieves feature selection. It also provides a mechanism for ranking features based upon the discrimination power of a subband. The more discriminant a subband, the better it is for classification. The results show that high classification accuracies are obtained by selecting subbands with high discrimination power. Moreover, subbands that are more stable i.e. have a higher probability of being selected provide better classification accuracies. Stability and discrimination power have been shown to have a direct relationship with classification accuracy. Hence, ADWPT acquires a subset of subbands that provide a highly discriminant and robust set of features for Meningioma subtype classification. Classification accuracies obtained are greater than 90% for most Meningioma subtypes. Consequently, ADWPT is a robust and adaptive technique which enables it to overcome the issue of high intra-class variation by statistically selecting the most useful subbands for meningioma subtype classification. It overcomes the issue of low inter-class variation by adapting to texture samples and extracting the subbands that are best for differentiating between the various meningioma subtype textures.
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Wibom, Carl. "Multivariate analyses of proteomic and metabolomic patterns in brain tumors." Doctoral thesis, Umeå universitet, Onkologi, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-25670.
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Glioblastoma multiforme (GBM) is the most common primary brain tumor. Given the current standard of care, the prognosis for patients diagnosed with this disease is still poor. There consequently exists a need to improve current treatments, as well as to develop new ones. Many obstacles however need to be overcome to facilitate this effort and one of these involves the development of improved methods to monitor treatment effects. At present, the effects of treatment are typically assessed by radiological means several months after its initiation, which is unsatisfactory for a fast growing tumor like GBM. It is however likely that treatment effects can be detected on a molecular level long before radiological response, especially considering many of the targeted therapies that are currently being developed. Biomarkers for treatment efficacy may be of great importance in the future individualization of brain tumor treatment. The work presented herein was primarily focused on detecting early effects of GBM treatment. To this end, we designed experiments in the BT4C rat glioma model in which we studied effects of both conventional radiotherapy and an experimental angiogenesis inhibitor, vandetanib. Brain tissue samples were analyzed using a high throughput mass spectrometry (MS) based screening, known as Surface Enhanced Laser Desorption/Ionization - Time of Flight - Mass Spectrometry (SELDI-TOF-MS). The vast amounts of data generated were subsequently analyzed by established multivariate statistical methods, such as Principal Component Analysis (PCA), Partial Least Squares (PLS), and Orthogonal Partial Least Squares (OPLS), developed for analysis of large and complex datasets. In the radiotherapy study we detected a protein spectrum pattern clearly related to tumor progression. We notably observed how this progression pattern was hampered by radiotherapy. The vandetanib study also revealed significant alterations of protein expression following treatment of different durations, both in tumor tissue and in normal brain contralateral to the tumor. In an effort to further elucidate the pathophysiology of GBM, particularly in relation to treatment, we collected extracellular fluid (ECF) samples from 11 patients diagnosed with inoperable GBM. The samples were collected by means of stereotactic microdialysis, both from within the contrast enhancing tumor and the brain adjacent to tumor (BAT). Samples were collected longitudinally from each patient in a time span of up to two weeks, during which the patient received the first five fractions of radiotherapy. The ECF samples were then analyzed by Gas Chromatography Mass Spectrometry (GC-MS) to screen them with respect to concentrations of low molecular weight compounds (metabolites). Suitable multivariate analysis strategies enabled us to extract patterns of varying metabolite concentrations distinguishing between samples collected at different locations in the brain as well as between samples collected at different time points in relation to treatment. In a separate study, we also applied SELDI-TOF-MS and multivariate statistical methods to unravel possible differences in protein spectra between invasive and non-invasive WHO grade I meningiomas. This type of tumor can usually be cured by surgical resection however sometimes it grows invasively into the bone, ultimately causing clinical problems. This study revealed the possibility to differentiate between invasive and non-invasive benign meningioma based on the expression pattern of a few proteins. Our approach, which includes sample analysis and data handling, is applicable to a wide range of screening studies. In this work we demonstrated that the combination of MS screening and multivariate analyses is a powerful tool in the search for patterns related to treatment effects and diagnostics in brain tumors.
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Lombardi, Ismael Augusto Silva [UNESP]. "Metilação e expressão do gene BRCA1 em meningiomas." Universidade Estadual Paulista (UNESP), 2013. http://hdl.handle.net/11449/88064.
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lombardi_ias_me_botfm.pdf: 529927 bytes, checksum: 6cb4e1254a86d1683806ac3cb6ca21b7 (MD5)Meningiomas são os tumores intracranianos primários mais comuns e correlacionam-‐se com câncer de mama, compatilhando características como incidência maior no sexo feminino, receptores para hormônios sexuais e crescimento a exposição a hormônios sexuais. O gene BRCA1 é amplamente estudado no câncer de mama hereditário e esporádico, entretanto, são poucos os trabalhos que correlacionam BRCA1 e meningiomas. O BRCA1 é gene de supressão tumoral, interagindo com outros oncogenes, atuando no reparo do DNA durante a divisão celular e modulando negativamente receptores de estrógeno e progesterona. Avaliar o padrão de metilação de e expressão de BRCA1 em meningiomas e tecidos controles, e a expressão de receptores de estrógeno e progesterona em meningiomas e controles, correlacionando estes dados com dados epidemiológicos da casuística. Casuística e métodos: pacientes com diagnóstico de meningiomas tiveram amostras tumorais colhidas durante cirurgias de rotina pela disciplina de Neurocirurgia da Faculdade de Medicina de Botucatu (FMB) e do Hospital Mário Gatti, em Campinas. Previamente, o projeto foi aprovado pelo Comitê de Ética em Pesquisa e cada paciente concordou em participar ao assinar o Termo de Consentimento Livre e Esclarecido. Amostras controle de aracnóide foram colhidas de cadáveres no serviço de necropsia da disciplina de Patologia da FMB. As amostras tumorais foram avaliadas para metilação de BRCA1 por PCR específica para metilação e os resultados avaliados por eletroforese. A expressão foi avaliada por PCR em tempo real os resultados dados em relação a amostras comtroles. A expressão de receptores de estrógeno (RE) e progesterona (RP) foram analisadas por imuno-histoquímica, conforme rotina da disciplina de Patologia da FMB. Foram avaliados 50 meningiomas entre...
Meningiomas are the most common primary intracranial tumors and correlate with breast cancer, shearing features like higher incidence in female, sexual hormone receptors and growth to exposure to sexual hormones. The gene is widely studied in hereditary and sporadic breast cancer, however, there are few studies that correlate BRCA1 and meningiomas. The BRCA1 is a tumor suppressor gene and interacts with other oncogenes by DNA repairing during cell division and also negative modulating estrogen and progesterone receptors. To assess the pattern of methylation and expression of BRCA1 in meningiomas and control tissues, and the expression of estrogen and progesterone receptors in meningiomas and control tissues, and to correlate these data with patients epidemiological data. Patients diagnosed with meningioma had collected tumors samples during routine surgeries by the discipline of Neurosurgery in Faculty of Medicine of Botucatu (FMB) and Mario Gatti Hospital in Campinas. Previously, the project was approved by the Research Ethics Committee and each patient agreed to participate by signing the Instrument of Consent. Control arachnoid samples were collected from cadavers during routine of necropsy of Pathology departament in FMB. The tumor samples were analyzed for methylation of BRCA1 by methylation specific PCR and the results were evaluated by electrophoresis. The expression was assessed by real-‐time PCR results given in relation to samples comtroles. The expression of estrogen receptors (ER) and progesterone (PR) were analyzed by immunohistochemistry, as routine in Pathology departament. There were 50 meningiomas between January 2009 to September 2012, 22 male and 28 female. The methylation of BRCA1 in meningiomas was statistically significant compared to control tissues... (Complete abstract click electronic access below)
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Lombardi, Ismael Augusto Silva. "Metilação e expressão do gene BRCA1 em meningiomas /." Botucatu : [s.n.], 2013. http://hdl.handle.net/11449/88064.
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Orientador: Adriana Camargo FerrasiCoorientador: Maria Inês de Moura Campos Pardini
Coorientador: Marco Antonio Zanini
Banca: Carlos Gilberto Carlotti Junior
Banca: Eny Maria Goloni-Bertollo
Resumo: Meningiomas são os tumores intracranianos primários mais comuns e correlacionam-‐se com câncer de mama, compatilhando características como incidência maior no sexo feminino, receptores para hormônios sexuais e crescimento a exposição a hormônios sexuais. O gene BRCA1 é amplamente estudado no câncer de mama hereditário e esporádico, entretanto, são poucos os trabalhos que correlacionam BRCA1 e meningiomas. O BRCA1 é gene de supressão tumoral, interagindo com outros oncogenes, atuando no reparo do DNA durante a divisão celular e modulando negativamente receptores de estrógeno e progesterona. Avaliar o padrão de metilação de e expressão de BRCA1 em meningiomas e tecidos controles, e a expressão de receptores de estrógeno e progesterona em meningiomas e controles, correlacionando estes dados com dados epidemiológicos da casuística. Casuística e métodos: pacientes com diagnóstico de meningiomas tiveram amostras tumorais colhidas durante cirurgias de rotina pela disciplina de Neurocirurgia da Faculdade de Medicina de Botucatu (FMB) e do Hospital Mário Gatti, em Campinas. Previamente, o projeto foi aprovado pelo Comitê de Ética em Pesquisa e cada paciente concordou em participar ao assinar o Termo de Consentimento Livre e Esclarecido. Amostras controle de aracnóide foram colhidas de cadáveres no serviço de necropsia da disciplina de Patologia da FMB. As amostras tumorais foram avaliadas para metilação de BRCA1 por PCR específica para metilação e os resultados avaliados por eletroforese. A expressão foi avaliada por PCR em tempo real os resultados dados em relação a amostras comtroles. A expressão de receptores de estrógeno (RE) e progesterona (RP) foram analisadas por imuno-histoquímica, conforme rotina da disciplina de Patologia da FMB. Foram avaliados 50 meningiomas entre... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: Meningiomas are the most common primary intracranial tumors and correlate with breast cancer, shearing features like higher incidence in female, sexual hormone receptors and growth to exposure to sexual hormones. The gene is widely studied in hereditary and sporadic breast cancer, however, there are few studies that correlate BRCA1 and meningiomas. The BRCA1 is a tumor suppressor gene and interacts with other oncogenes by DNA repairing during cell division and also negative modulating estrogen and progesterone receptors. To assess the pattern of methylation and expression of BRCA1 in meningiomas and control tissues, and the expression of estrogen and progesterone receptors in meningiomas and control tissues, and to correlate these data with patients epidemiological data. Patients diagnosed with meningioma had collected tumors samples during routine surgeries by the discipline of Neurosurgery in Faculty of Medicine of Botucatu (FMB) and Mario Gatti Hospital in Campinas. Previously, the project was approved by the Research Ethics Committee and each patient agreed to participate by signing the Instrument of Consent. Control arachnoid samples were collected from cadavers during routine of necropsy of Pathology departament in FMB. The tumor samples were analyzed for methylation of BRCA1 by methylation specific PCR and the results were evaluated by electrophoresis. The expression was assessed by real-‐time PCR results given in relation to samples comtroles. The expression of estrogen receptors (ER) and progesterone (PR) were analyzed by immunohistochemistry, as routine in Pathology departament. There were 50 meningiomas between January 2009 to September 2012, 22 male and 28 female. The methylation of BRCA1 in meningiomas was statistically significant compared to control tissues... (Complete abstract click electronic access below)
Mestre
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Mörén, Lina. "Metabolomics and proteomics studies of brain tumors : a chemometric bioinformatics approach." Doctoral thesis, Umeå universitet, Kemiska institutionen, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-111309.
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The WHO classification of brain tumors is based on histological features and the aggressiveness of the tumor is classified from grade I to IV, where grade IV is the most aggressive. Today, the correlation between prognosis and tumor grade is the most important component in tumor classification. High grade gliomas, glioblastomas, are associated with poor prognosis and a median survival of 14 months including all available treatments. Low grade meningiomas, usually benign grade I tumors, are in most cases cured by surgical resection. However despite their benign appearance grade I meningiomas can, without any histopathological signs, in some cases develop bone invasive growth and become lethal. Thus, it is necessary to improve conventional treatment modalities, develop new treatment strategies and improve the knowledge regarding the basic pathophysiology in the classification and treatment of brain tumors. In this thesis, both proteomics and metabolomics have been applied in the search for biomarkers or biomarker patterns in two different types of brain tumors, gliomas and meningiomas. Proteomic studies were carried out mainly by surface enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF-MS). In one of the studies, isobaric tags for relative and absolute quantitation (iTRAQ) labeling in combination with high-performance liquid chromatography (HPLC) was used for protein detection and identification. For metabolomics, gas-chromatography time-of-flight mass spectrometry (GC-TOF-MS) has been the main platform used throughout this work for generation of robust global metabolite profiles in tissue, blood and cell cultures. To deal with the complexity of the generated data, and to be able to extract relevant biomarker patters or latent biomarkers, for interpretation, prediction and prognosis, bioinformatic strategies based on chemometrics were applied throughout the studies of the thesis. In summary, we detected differentiating protein profiles between invasive and non-invasive meningiomas, in both fibrous and meningothelial tumors. Furthermore, in a different study we discovered treatment induce protein pattern changes in a rat glioma model treated with an angiogenesis inhibitor. We identified a cluster of proteins linked to angiogenesis. One of those proteins, HSP90, was found elevated in relation to treatment in tumors, following ELISA validation. An interesting observation in a separate study was that it was possible to detect metabolite pattern changes in the serum metabolome, as an effect of treatment with radiotherapy, and that these pattern changes differed between different patients, highlighting a possibility for monitoring individual treatment response. In the fourth study of this work, we investigated tissue and serum from glioma patients that revealed differences in the metabolome between glioblastoma and oligodendroglioma, as well as between oligodendroglioma grade II and grade III. In addition, we discovered metabolite patterns associated to survival in both glioblastoma and oligodendroglioma. In our final work, we identified metabolite pattern differences between cell lines from a subgroup of glioblastomas lacking argininosuccinate synthetase (ASS1) expression, (ASS1 negative glioblastomas), making them auxotrophic for arginine, a metabolite required for tumor growth and proliferation, as compared to glioblastomas with normal ASS1 expression (ASS1 positive). From the identified metabolite pattern differences we could verify the hypothesized alterations in the arginine biosynthetic pathway. We also identified additional interesting metabolites that may provide clues for future diagnostics and treatments. Finally, we were able to verify the specific treatment effect of ASS1 negative cells by means of arginine deprivation on a metabolic level.
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Prager, Briana C. "THE MENINGIOMA ENHANCER LANDSCAPE DELINEATES PROGNOSTIC SUBGROUPS AND DRIVES DRUGGABLE DEPENDENCIES." Case Western Reserve University School of Graduate Studies / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=case1595620620551252.
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Ghasimi, Soma. "Genotype-phenotype studies in brain tumors." Doctoral thesis, Umeå universitet, Onkologi, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-83185.
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Meningioma and glioma are the most common primary brain tumors, but their etiologies are largely unknown. Although meningioma is usually benign, their intracranial location can lead to lethal consequences, and despite progress in surgery, radiotherapy, and chemotherapy the prognosis for patients with glioma remains poor. The only well-established environmental risk factor for meningioma and glioma is ionizing radiation. Evidence for inherited predisposition to meningioma and glioma is provided by a number of rare inherited syndromes where collectively these diseases account for only a small proportion of the twofold increased risk of brain tumors seen in first-degree relatives for meningioma and glioma patients. It is very possible that much of the excess familial risk is a consequence of co-inheritance of multiple low-risk genetic variations. With this in mind, the aims of the studies in this thesis were to discover genetic risk variants influencing the probability of acquiring the disease and to identify the association between risk variants on the tumor phenotype. To identify genetic variants influencing meningioma risk, a comprehensive tagging of the selected genes in a case-control study was performed. We identified nine risk variants in EGF, ERBB2, and LRIG2 genes. However, these findings could not be confirmed in another larger independent dataset. In addition, the study identified a correlation between LRIG2 protein expression and ER status when analyzed with different parameters. In a separate study with a larger sample of meningioma patients, the same correlation between LRIG2 and ER status was observed. To explore the potential association between reported germline risk variants and somatic genetic events, matched tumor and blood samples from glioma patients were analyzed by SNP array. The results identified correlations between EGFR gene variants and somatic aberrations within the EGFR locus and CDKN2A/B locus. To further study the relationship between germline risk variants and tumor phenotype, the same patient material was used and analyzed by three different techniques: SNP array, IHC, and FISH. The results revealed EGFR risk variants effecting copy number variation of the EGFR gene and the expression of the IDH1 and p53. Further comparison between different techniques such as SNP array and FISH analysis revealed the difficulty in achieving consistent results with different techniques. To summarize, the glioma studies show a link between genotype and phenotype where genetic risk variants in the EGFR gene were found to be associated with specific somatic aberrations. These associations are biologically interesting because EGFR is involved in multiple cellular processes. Additional studies of the direct functional role of these observations need to be conducted to elucidate the molecular mechanisms underlying the identified association between germline gene variants and somatic aberrations. For the meningioma studies, no significant risk variants influencing the disease were found but a correlation between LRIG2 and ER status was observed. This result suggests a potential role for the LRIG protein in the pathogenesis of meningioma, but more studies are needed to confirm this hypothesizes.Cancer research foundation in northern Sweden and Lions cancer research foundation at Umeå university
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Hansson, Caisa Marie. "Analysis of Genetic Alterations in Patients Affected with Neurofibromatosis Type 2 and its Associated Tumors." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-6511.
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Buckley, Patrick. "Development and Application of Microarray-Based Comparative Genomic Hybridization : Analysis of Neurofibromatosis Type-2, Schwannomatosis and Related Tumors." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4786.
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Almeida, Luciana Oliveira de. "Análise epigenética e de polimorfismos em tumores extra-axiais do sistema nervoso." Universidade de São Paulo, 2009. http://www.teses.usp.br/teses/disponiveis/17/17135/tde-02032010-121437/.
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Os tumores extra-axias do sistema nervoso são de localização extra-cerebral e na maioria das vezes benignos; meningiomas, schwanomas e metástases fazem parte deste grupo. O aparecimento de um tumor ocorre a partir do acúmulo de alterações genéticas e epigenéticas nas células. Para entender o mecanismo molecular da progressão tumoral e a formação de metástases é indispensável identificar os genes que acumulam essas alterações. Sendo assim, este trabalho teve como objetivo analisar o perfil de metilação dos genes TP16, TP53, DAL-1, GSTP-1, MEN-1, NDRG2 e das DNA metiltransferases 3A, 3B e 3L e sua associação com os tumores extra-axiais e ainda, avaliar, através de um estudo caso-controle, a influência dos SNPs TP53 Pro47Ser e Arg72Pro, EGF + 61, GSTP-1 Ile105Val e WRN Cys1367Arg no desenvolvimento e prognóstico desses tumores. A técnica utilizada para a análise de hipermetilação foi a MSP, e através dela observamos que a atividade das DNMTs não está associada à metilação dos tumores extra-axiais e ainda, os perfis de metilação das DNMTs de novo não estão associados com alterações no padrão de metilação dos genes TP16, TP53, DAL-1, GSTP-1, MEN- 1 e NDRG2. Observamos que a metilação do gene TP53 está associada principalmente aos tumores de maior grau de malignidade, a uma deficiência na resposta a tratamentos e, conseqüentemente, a um maior número de óbitos. A metilação do gene TP16 está envolvida mais freqüentemente na formação de schwanomas e a de NDRG2 na progressão dos meningiomas. A análise de polimorfismos foi realizada através da técnica de PCR-RFLP e observamos diferenças nas distribuições genotípicas entre pacientes e controles nos SNPs TP53 Pro47Ser e Arg72Pro, EGF + 61 e GSTP-1 Ile105Val, onde as variantes Ser47, Pro72, EGF G61 e Val105 foram observadas com maior freqüência entre os portadores de tumores extra-axiais. Dessa forma, estas variantes podem ser fatores de susceptibilidade para o desenvolvimento dos tumores.The extra-axial brain tumors have extra-brain localization and in most of the time they are benign, meningiomas, schwannomas and metastasis are included in this group. The appearance of a tumor occurs because of the accumulation of genetic and epigenetic alterations in the cells. In order to understand the molecular mechanism of the tumor progression and the metastasis formation it is important to identify the genes that accumulate the alterations. Thereby, the objective of this study was to analyze the methylation profile of the genes TP16, TP53, DAL-1, GSTP-1, MEN-1, NDRG2 and the DNA methyltransferases 3A, 3B and 3L and their association with the extra-axial brain tumors. Another purpose was to determine, in a case-control study, the roles of the TP53 Pro47Ser and Arg72Pro, EGF + 61, GSTP-1 Ile105Val and WRN Cys1367Arg SNPs in the development and prognosis of these tumors. We used the MSP to screen the hypermethylation profile and we observed no association between the DNMTs activity and the hypermethylation of the tumors. We also did not find association between the methylation of the DNMTs de novo and alterations in the methylation profile of the genes TP16, TP53, DAL-1, GSTP-1, MEN-1 and NDRG2. We observed that TP53 hypermethylation was associated with the high grade tumors, a poor response to the treatments and, consequently, the high number of obits. The TP16 methylation was involved with the shwannomas formation and the NDRG2 gene was involved in the meningiomas progression. For the polymorphism analysis, we used the PCR-RFLP technique and we observed differences in the genotype distributions between cases and controls of TP53 Pro47Ser and Arg72Pro, EGF + 61 and GSTP-1 Ile105Val SNPs, where the variants Ser47, Pro72, EGF G61 and Val105 were more frequent in patients than in controls. Thus, these variants can be important factors of susceptibility to the tumor development.
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Rosa, Marcella Suelma de Torrecillas. "Expressão tecidual e sérica de microRNAs associados a receptores de estrógeno e progesterona em meningiomas grau I, II e III." Universidade de São Paulo, 2018. http://www.teses.usp.br/teses/disponiveis/17/17137/tde-09112018-110503/.
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Os meningiomas são os tumores primários do Sistema Nervoso Central (SNC) mais frequentes e representam 35,5% dos casos considerando-se todas as faixas etárias. Apesar dos progressos ocorridos nas últimas décadas, a tumorigênese dos meningiomas ainda permanece como um desafio. Há um consenso da necessidade de ferramentas moleculares para ajudar tanto no diagnóstico quanto no prognóstico dos meningiomas. Neste contexto, alguns trabalhos demonstram a importância do papel dos receptores de estrógeno e progesterona, assim como o entendimento das alterações nos níveis de expressão dos microRNAs (miRNAs) na tumorigênese dos meningiomas. Alguns estudos demonstram que o perfil de expressão sérico dos miRNAs tem correlação com a classificação e evolução clínica, sendo de grande interesse o uso desse material por se tratar de um procedimento não-invasivo, ou seja, como biomarcadores. Objetivos: avaliar o perfil de expressão tecidual e sérica de microRNAs associados as vias dos receptores de estrógeno e progesterona em meningiomas grau I, II e III. Pacientes e métodos: foram utilizadas amostras de tecido e plasma de 40 pacientes com meningiomas grau I, II e III. Para a análise da expressão dos miRNAs miR-34a, miR-143, miR-145 e miR-335 foi utillizada a técnica de PCR em tempo real. Resultados: os miRNAs: miR-34a e miR-145 apresentaram diferença estatística significativa nas amostras de tecido tumoral entre os grupos estudados com menor expressão nas amostras de meningiomas grau II quando comparadas as amostras grau I e III. Não observamos diferença estatística estatística significativa na expressão dos miRNAs nas amostras de plasma. Conclusão: os miRNAs selecionados não apresentaram correlação com a progressão tumoral em meningiomas.Meningiomas are the most common primary Central Nervous System (CNS) tumors, accounting for 35.5% of the cases, considering all age groups. Despite the progress made in recent decades, the tumorigenesis of meningiomas still remains a challenge. There is a consensus of the need for molecular tools to assist both diagnosis and prognosis of meningiomas. In this context, some studies demonstrate the importance of the role of estrogen and progesterone receptors, as well as the understanding of alterations in microRNA (miRNAs) expression levels in the tumorigenesis of meningiomas. Some studies have shown that the serum expression profile of the miRNAs correlates with the classification and clinical evolution, being of great interest the use of this material because it is a non-invasive procedure, i.e., as biomarkers. Objectives: To evaluate the tissue and serum expression profile of microRNAs associated with the estrogen and progesterone receptor pathways in meningiomas grade I, II and III. Patients and methods: tissue and blood samples from 40 patients with grade I, II and III meningiomas were used. For analysis of miRNA expression miR-34a, miR-143, miR-145 and miR-335 was used the real-time PCR technique. Results: miRNAs: miR-34a and miR-145 presented a significant statistical difference in the tumor tissue samples between the groups with lower expression in the samples of grade II meningiomas when compared to samples I and III. We did not observe statistically significant statistical difference in miRNA expression in blood samples. Conclusion: the selected miRNAs showed no correlation with tumor progression in meningiomas.
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Carneiro, Vinicius Marques. "Perfil de expressão tecidual e plasmática dos microRNAs miR-130a, miR-181c e miR-181d em meningiomas grau I, II e III." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/17/17137/tde-01022016-155451/.
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Introdução: Os meningiomas são neoplasias intracranianas de crescimento lento que se originam das células meningoteliais da aracnoide e representam os tumores intracranianos mais comuns, contabilizando 13-26% deste total, sendo um dos primeiros tumores sólidos a terem alterações genéticas identificadas. Inúmeros tem sido os avanços para a melhor compreensão das vias moleculares correlacionadas com a tumorigênese e progressão tumoral dos meningiomas, neste contexto tem se destacado o papel dos microRNAs que são RNAs não-codificantes (ncRNAs) constituídos por 19 a 25 nucleotídeos, cuja função é o silenciamento do RNAm em nível póstranscricional. Portanto, o objetivo do nosso estudo foi avaliar a expressão tecidual e plasmática dos miRNAs miR-181d, miR-181c e miR-130a. Pacientes e métodos: Os miRNAs miR-181d, miR-181c e miR-130a foram selecionados a partir de estudo prévio do nosso grupo pela técnica de análise em larga escala de microarrays, onde foram comparados meningiomas grau I com amostras controles de aracnóides. Neste trabalho foi avaliada expressão destes miRNAs no tecido tumoral e plasma de meningiomas grau I, II e III. Resultados: O miR-181d apresentou-se hiperexpresso nos grupos estudados, no tecido tumoral quanto no plasma. O nível de expressão foi maior de acordo com a progressão do grau do tumor. Os miR-181c e miR-130a não apresentaram diferença estatística nos grupos estudados em ambos tecido tumoral e plasma. Conclusões: O miR-181d tem potencial para ser utilizado como biomarcador para meningiomas e está associado com sua progressão tumoral.Introduction: Meningiomas are intracranial tumors of slow growth that originate from meningothelial arachnoid cells and represents the most common intracranial tumors, accounting for 13-26% of this total, beeing one of the first solid tumors to have identified genetic alterations There are technological advances available to a better understanding of the molecular pathways correlated with tumorigenesis and tumor progression of meningiomas. The role of microRNAs in this process is very importante. MicroRNAs are non-coding RNAs (ncRNAs) consisting of 19 to 25 nucleotides, with function of mRNA silencing post-transcriptional level. The aim of our study was to evaluate the tissue expression and plasma of miRNAs miR-181d, miR-181c and miR-130a. Patients and methods: The miRNAs miR-181d, miR-181c and miR-130a were selected from a previous study of our group by analysis technique on large scale called microarrays, which were compared meningiomas grade I with arachnoid controls samples. In this study, we evaluated expression of these miRNAs in tumor tissue and plasma meningiomas grade I, II and III. Results: The miR-181d was presented upregulated in the all groups in both tumor tissue and in plasma. The level of expression was increased according to the progression of tumor grade. The miR-181c and miR-130a showed no statistical difference in the groups studied in both tumor tissue and plasma. Conclusions: The miR-181d has potential as a biomarker for meningiomas and is associated with tumor progression.
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Bassiri, Kayleigh. "Identifying common therapeutic targets in Merlin-deficient brain tumours." Thesis, University of Plymouth, 2016. http://hdl.handle.net/10026.1/8068.
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Neurofibromatosis type 2 (NF2) is an autosomal dominant inherited condition that predisposes individuals to develop multiple nervous system tumours, primarily schwannoma, meningioma and ependymoma. NF2 is characterised by loss of the tumour suppressor protein Merlin, caused by bi-allelic mutations of the encoding gene NF2 or by loss of heterozygosity. These tumours can occur either sporadically or as part of the NF2 condition. The majority are slow growing and display benign features, but this benignancy renders them largely unresponsive to classic chemotherapeutic agents leaving surgery and radiosurgery as the only remaining treatment options. Depending on their location, NF2-related tumours can cause a number of side effects, including nausea, balance problems, and in some cases hearing and/or vision loss. Phosphorylation is a key regulatory mechanism leading to changes in cell signalling. By identifying phosphoproteins that are significantly activated in tumour cells, novel therapies can be developed aiming to specifically target the phosphorylated status of these proteins thus ‘switching off’ the signalling cascade. The objective of this study is to identify and validate common targets in both Merlin-deficient meningioma and schwannoma to eventually exploit in novel therapeutic approaches. Using phosphoprotein purification followed by mass spectrometry analysis, we identified Signal Transducer and Activator of Transcription 1 (STAT1), phosphorylated at Serine (S) 727 and Tyrosine (Y) 701, PDZ and LIM domain protein 2 (PDLIM2), Heat Shock 70kDa Protein 1A (HSPA1A) and Filamin B (FLNB) as potential common, novel therapeutic targets. We validated these candidates in human primary meningioma and schwannoma tumour cells using a variety of techniques. We also showed that specific 7 knockdown of STAT1 and PDLIM2 was related to a significant decrease in cellular proliferation. Additionally, we performed co-immunoprecipitation using PDLIM2 as the bait protein and identified STAT1, HSPA1A and FLNB as binding partners, suggesting a novel interaction network involving all of the potential targets identified in this study. We also identified activation of several pathways and/ or biological processes in both tumour types that warrant further investigation i.e. endocytosis in schwannoma and the proteasome in meningioma. In conclusion, with our approach we substantially increased the overall body of knowledge regarding the proteome and phosphoproteome of meningioma and schwannoma. We generated a comprehensive set of data that highlighted several potential therapeutic targets and dysregulated pathways which will be further investigated.
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Valer, Gonzales Dante. "Incidencia, localización y recidiva de los meningiomas cerebrales." Bachelor's thesis, Universidad Nacional Mayor de San Marcos, 2014. https://hdl.handle.net/20.500.12672/13063.
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Introducción: Conociendo la incidencia, localización más frecuente y los factores que influyen en la recurrencia de los meningiomas, mejoraría el pronóstico de los pacientes operados de meningiomas cerebrales.
Marco teórico: Los meningiomas son tumores que constituyen el 20% de los tumores cerebrales, la mayoría de ellos son asintomáticos, con un predominio femenino del 3:1. Existen varios factores que influyen en la recidiva de los meningiomas que debemos conocer para mejor planificación quirúrgica y manejo complementario de ser necesario.
Objetivos: Determinar si la localización, el tipo y grado histológico, el grado de resección quirúrgica, son factores determinantes en la recurrencia de los meningiomas en los pacientes post operados de meningiomas cerebrales.
Materiales y métodos: Se realizó un estudio de investigación retrospectivo, descriptivo y analítico, de casos y controles, trabajando con un grupo de historias clínicas de los pacientes post operados de meningiomas intracerebrales durante el mes de enero del 2001 hasta diciembre del 2010, con un lapso de observación mínimo de 12 meses, siendo aquellos que recidivaron los casos y aquellos que no recidivaron los controles.
Resultados e interpretación: Se incluyeron en la investigación 169 pacientes entre los 16 y 81 años, encontrando una predominancia femenina de 2.5: 1 de mujeres y varones. Respecto a la localización encontramos que el 37.3% fue base de cráneo, el 29% de la convexidad, el 26.6% parasagital, 3% ventriculares y el 4,2% meningioma múltiple y meningiomatosis. Evaluando el tipo histológico encontramos que el 33.7% fueron de tipo transicional, el 25.4% fibroblástico, 14.8% meningotelial, angioblastico 7.1%, psamomatoso 5.9%, 4.1% atípico, 4.1% maligno y 0.6% anaplásico. Respecto al grado de resección quirúrgica en 60.9% se realizó Simpson II, en el 33.7% Simpson I, en el 5.3% Simpson III y en ningún paciente se realizó Simpson IV o V. Encontramos que el 16% de nuestros pacientes, presentan tumor residual, luego de un seguimiento entre 1 – 10 años. Relacionando la extensión de la cirugía con el Tumor residual, observamos un 80% se encuentra en los que se realizó Simpson III, mientras que en los de Simpson I el porcentaje de recidiva fue <3.63%. Analizando el tipo histológico y tumor residual, observamos que aquellos con tipo histológico como son meningotelial, fibroblastico, transicional, psamomatoso, presentan un porcentaje bajo de recurrencia entre el 8.7% al 14.28%, los de tipo histológico maligno tienen un grado de recurrencia de 57.14%.
Conclusiones: La mayor incidencia de los meningiomas en el sexo femenino esta en relación a factores hormonales. La extensión de la Cirugía (Simpson), el tipo histológico, la localización, mostró una asociación significativa con la presencia de tumor residual en el grupo poblacional evaluado.Trabajo académico
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SUGIURA, MITSUO, and HIROJI KUCHIWAKI. "Septic Shock with Hyperglycemia Induced by Hypothalamic Dysfunction after Removal of Large Parasagittal Meningioma." Nagoya University School of Medicine, 1988. http://hdl.handle.net/2237/17501.
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Wayhs, Samia Yasin. "Influência da abordagem cirúrgica na ressecção dos meningiomas petroclivais." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2015. http://hdl.handle.net/10183/148212.
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Meningiomas petroclivais são tumores da base do crânio desafiadores para ressecção cirúrgica devido a sua localização profunda e relação com estruturas neurovasculares vitais. Geralmente são lesões benignas, mas podem envolver ou infiltrar o osso da base do crânio, dura-máter, tronco encefálico e todas as estruturas neurovasculares desta região, tornando a remoção total difícil sem causar déficits neurológicos. O objetivo deste estudo é revisar uma série de casos de meningiomas petroclivais tratados cirurgicamente em centro de referência de base de crânio, considerando os fatores determinantes para a escolha da abordagem. A casuística foi analisada com coleta retrospectiva dos dados. Devido à dificuldade de acesso, essas lesões geralmente requerem diferentes abordagens cirúrgicas e apresentam dificuldades cirúrgicas distintas. Embora as abordagens fronto-órbito-zigomática, petrosas, incluindo présigmoide retrolabiríntica, translabiríntica e petrosectomia total, e a retrossigmoide sejam as mais utilizadas para ressecção destes tumores, não foi realizado até o presente momento estudo comparativo que determine qual abordagem apresenta maior grau de ressecção cirúrgica associada a menor taxa de morbidade.Petroclival meningiomas are challenging skull base tumors for surgical resection because of its deep location and their relationship to vital neurovascular structures. They are usually benign, but may involve or infiltrate the bone of the skull base, dura, brain stem and all neurovascular structures in this region, making it difficult to completely remove without causing neurological deficits. The aim of this study is to review a surgical series of petroclival meningioma treated in a referral center for skull base tumors, considering the determining factors to the choice of approach. The casuistry was analyzed with retrospective data collection. Due to difficult access, these injuries usually require different surgical approaches and have different surgical difficulties. Although the fronto-orbital-zygomatic, petrous, including retrolabyrinthine pre-sigmoid, translabyrinthine and total petrosectomy, and retrosigmoid are frequently used for resection of these tumors, it has not been realized to date comparative study to determine which approach has greater degree of surgical resection associated with lower morbidity rate.
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Galvani, Aline Faria [UNESP]. "Análise da Frequência de Polimorfismos nos genes IL28B e IL28R1 em pacientes acometidos por Meningioma." Universidade Estadual Paulista (UNESP), 2015. http://hdl.handle.net/11449/134110.
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Os meningiomas são os tumores mais frequentes do Sistema Nervoso Central e sua classificação é dada quanto ao tipo celular envolvido e grau de malignidade. Os intérferons (IFNs) foram inicialmente associados à resposta antiviral, contudo, estudos posteriores evidenciaram o envolvimento dessas citocinas na regulação do crescimento celular e no efeito imunomodulatório. A Interleucina 28B (IL28B), membro da família dos IFNs do tipo III, parece estar envolvida na resposta imune antiviral e antitumoral. Sendo assim, o objetivo do presente estudo foi avaliar a frequência de variações genéticas em IL28B e IL28R1 em pacientes acometidos por Meningiomas. Sessenta paciente tratados pelo serviço de Neurocirurgia da UNESP de Botucatu/SP foram incluídos neste estudo. A análise do polimorfismo rs12979860 C/T teve significância estatística quando comparou-se a frequência genotípica da população brasileira em relação a presente casuística. Foi descrito a detecção de novas variações genéticas (missense e silent) nos genes IL28B e IL28R1 ao comparar com as respectivas sequencias referencias disponíveis em banco de dados (NCBI). Estes dados sugerem uma importante relação destas variações genéticas em relação a estrutura e função das proteínas envolvidas, entretanto um estudo mais aprofundado das consequências dessas alterações na gênese e/ou progressão dos meningiomas devem ser considerado
Meningiomas are the most common tumors of the central nervous system, despite being benign and grow slowly, can recur in case of incomplete surgical resection. They are classified according to the cells involved and their rate of malignancy. The role of the immune system in preventing the emergence and progression of tumors has been the subject of many studies in the field of tumor immunology. Interferon (IFNs) were originally associated with antiviral response, however, subsequent studies revealed the involvement of these cytokines in the regulation of cell growth and their immunomodulatory effect.Thus, the aim of this study was to analyze the genetic variation frequency of IL28B and IL28R1 in patients with meningioma. Sixty patients treated by UNESP Neurosurgery service of Botucatu/SP were included in this study. Polymorphism rs12979860 C/T analysis showed statistical significance when compared with healthy Brazilian's genotypic frequency. New genetic variation (missense and silent) were detected in IL28B and IL28R1 through reference sequences analysis (NCBI). These data support an important relation of these genetic variations related to protein functions, however other studies of the consequences of these changes in the development and progression of meningiomas should be considered
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Galvani, Aline Faria. "Análise da Frequência de Polimorfismos nos genes IL28B e IL28R1 em pacientes acometidos por Meningioma /." Botucatu, 2015. http://hdl.handle.net/11449/134110.
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Orientador: Maria Inês de Moura Campos PardiniCoorientador: Adriana Camargo Ferrasi
Banca: Sílvia Helena Barem Rabenhorst
Banca: Marcelo Lima Ribeiro
Resumo: Os meningiomas são os tumores mais frequentes do Sistema Nervoso Central e sua classificação é dada quanto ao tipo celular envolvido e grau de malignidade. Os intérferons (IFNs) foram inicialmente associados à resposta antiviral, contudo, estudos posteriores evidenciaram o envolvimento dessas citocinas na regulação do crescimento celular e no efeito imunomodulatório. A Interleucina 28B (IL28B), membro da família dos IFNs do tipo III, parece estar envolvida na resposta imune antiviral e antitumoral. Sendo assim, o objetivo do presente estudo foi avaliar a frequência de variações genéticas em IL28B e IL28R1 em pacientes acometidos por Meningiomas. Sessenta paciente tratados pelo serviço de Neurocirurgia da UNESP de Botucatu/SP foram incluídos neste estudo. A análise do polimorfismo rs12979860 C/T teve significância estatística quando comparou-se a frequência genotípica da população brasileira em relação a presente casuística. Foi descrito a detecção de novas variações genéticas (missense e silent) nos genes IL28B e IL28R1 ao comparar com as respectivas sequencias referencias disponíveis em banco de dados (NCBI). Estes dados sugerem uma importante relação destas variações genéticas em relação a estrutura e função das proteínas envolvidas, entretanto um estudo mais aprofundado das consequências dessas alterações na gênese e/ou progressão dos meningiomas devem ser considerado
Abstract: Meningiomas are the most common tumors of the central nervous system, despite being benign and grow slowly, can recur in case of incomplete surgical resection. They are classified according to the cells involved and their rate of malignancy. The role of the immune system in preventing the emergence and progression of tumors has been the subject of many studies in the field of tumor immunology. Interferon (IFNs) were originally associated with antiviral response, however, subsequent studies revealed the involvement of these cytokines in the regulation of cell growth and their immunomodulatory effect.Thus, the aim of this study was to analyze the genetic variation frequency of IL28B and IL28R1 in patients with meningioma. Sixty patients treated by UNESP Neurosurgery service of Botucatu/SP were included in this study. Polymorphism rs12979860 C/T analysis showed statistical significance when compared with healthy Brazilian's genotypic frequency. New genetic variation (missense and silent) were detected in IL28B and IL28R1 through reference sequences analysis (NCBI). These data support an important relation of these genetic variations related to protein functions, however other studies of the consequences of these changes in the development and progression of meningiomas should be considered
Mestre
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Simis, André. "Edema peritumoral em meningiomas benignos: correlação com fatores clínicos, radiológicos, cirúrgicos e com recorrência tumoral." Universidade de São Paulo, 2007. http://www.teses.usp.br/teses/disponiveis/5/5138/tde-12022008-132122/.
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INTRODUÇÃO: O edema peritumoral (EP) está presente em aproximadamente 60% dos meningiomas. Os fatores responsáveis pela formação do edema e sua importância clínica permanecem como foco de discussão. OBJETIVOS: Analisar a correlação entre a presença de edema com características clínicas, cirúrgicas, radiológicas e recorrência tumoral. MÉTODOS: Foram selecionados 61 pacientes portadores de meningiomas benignos submetidos a tratamento cirúrgico pelo Grupo de Tumores Encefálicos e Metástases do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. Foram incluídos no estudo os portadores de meningiomas benignos submetidos a ressecção tumoral completa (Simpson 1 e 2). Foram excluídos pacientes portadores de meningiomas malignos ou atípicos e aqueles localizados em tubérculo selar, seio cavernoso, forame magno, intraventriculares e região petroclival. RESULTADOS: Encontramos correlação entre as maiores medidas de edema peritumoral e recorrência tumoral (p = 0,042) e tumores com margens irregulares (p < 0,011) na análise bivariada. Além disso, os pacientes que apresentaram maiores volumes tumorais apresentaram maiores medidas de edema (p = 0,035) e nos pacientes com menores medidas de edema a localização tentorial foi mais freqüente (p = 0,032). Verificamos que ao estudo de regressão logística, o EP apresenta correlação com tumores maiores que 40 cm3 (Odds ratio=15,977), crises convulsivas (Odds ratio=3,469) e para cada cm3 acrescida ao tamanho tumoral o risco de edema cresce 1,082 vez (Odds ratio). CONCLUSÕES: Considerando os resultados obtidos, o EP esteve associado a maior recorrência tumoral, tumores multilobulados, grandes e a presença de crises convulsivas. A localização tentorial mostrou-se como um fator protetor ao EP. O EP pode estar associado a um potencial invasivo aumentado em meningiomas. Desta forma, o seu estudo aprofundado poderá trazer dados adicionais para o esclarecimento dos mecanismos de formação dos meningiomas e de seu comportamento biológico levando ao melhor manejo clínico dos pacientes.INTRODUCTION: Approximately 60% of meningiomas are associated with peritumoral edema.Various causative factors have been discussed in the literature. PURPOSES: Investigate the correlation of peritumoral edema with clinical, radiological and surgical aspects, and recurrence rate of meningiomas. METHODS: Sixty one benign meningiomas submitted to surgical treatment by the Group of Brain Tumors and Metastasis of the Division of Neurosurgery of the Hospital das Clínicas of São Paulo Medical School of São Paulo University. All patients underwent complete surgical ressection (Simpson 1 and 2) and were excluded the atypical and malignant hystopathological grades. The tumors located in the cavernous sinus, tuberculum sellae region, foramen magnum region, ventricular space and petroclival region were excluded. RESULTS: Edema extention had a positive correlation with the higher recurrence rates (p = 0,042) and with the presence of irregular margins (p < 0,011) on bivariate analysis. Meningiomas with greater edema sizes also showed correlation with large meningiomas (p = 0,035) and the ones with smaller edema sizes correlated with the tentorial location (p=0,032). Multivariate analysis showed an association between peritumoral brain edema and the presence of seizures (Odds ratio=3,469), large meningiomas (Odds ratio=15,977), and for each cubic centimeter added to its size, the risk of edema increased 1,082 times (Odds ratio). CONCLUSION: Peritumoral brain edema correlated with recurrence, irregular margins, seizures and larger tumors. The tentorial location demonstrated smaller edema sizes. Peritumoral brain edema may be related to meningioma\'s invading potentiality and may play a role in the recurrence pontential of the tumor. As a consequence, it\'s reasonable to consider edema\'s presence as an additional factor to be taken into account when arranging layout of strategies for meningiomas treatment.
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Andersson, Ulrika. "Experimental studies in brain tumours : with special regard to multidrug resistance and the ErbB-family." Doctoral thesis, Umeå : Strålningsvetenskaper, Umeå universitet, 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-521.
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DIAZ, JUAN. "Tumeurs cerebrales a expression psychiatrique : a propos d'un cas de meningiome temporal." Université Louis Pasteur (Strasbourg) (1971-2008), 1993. http://www.theses.fr/1993STR1M042.
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Coelho, Francisco Manuel Leão de Sá. "Análise do tempo de sobrevida após o diagnóstico de meningioma intracraniano canino e sua relação com os sinais neurológicos, localização tumoral e tratamento instituído." Master's thesis, Universidade de Lisboa, Faculdade de Medicina Veterinária, 2021. http://hdl.handle.net/10400.5/21683.
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Dissertação de Mestrado Integrado em Medicina VeterináriaRESUMO - Para a análise do tempo de sobrevida de cães com meningioma intracraniano canino em função do tratamento aplicado, e avaliação dos sinais neurológicos e localização tumoral como possíveis fatores de prognóstico, foi realizado um estudo retrospetivo com inclusão de 49 cães com diagnóstico presuntivo (n=42) ou definitivo (n=7) de meningioma intracraniano, agrupados consoante o tratamento instituído: farmacológico (n=38) – paliativo (n=32) ou quimioterapia (n=6) – e cirúrgico (n=11) – cirurgia (n=7) ou cirurgia e quimioterapia (n=4). A mediana do tempo de sobrevida (MTS) para o grupo submetido a tratamento paliativo foi de 147 dias (4,9 meses), já quando apenas executada cirurgia esta foi de 129 dias (4,3 meses). A administração de quimioterapia isolada ou adjuvante à cirurgia resultou numa MTS de 360 dias (11,8 meses) e 468 dias (15,6 meses), respetivamente, demonstrando um efeito positivo no tempo de sobrevida dos cães com meningioma intracraniano. Não se verificou diferença entre as curvas de distribuição de tempos de sobrevida de cada grupo de tratamento (p=0,156). Contudo, para p<0,1, os cães com meningioma intracraniano presuntivo inseridos no grupo de tratamento paliativo tinham cerca de 1,926 e 2,832 vezes maior probabilidade de morrer a qualquer instante do que se incluídos em outro grupo de tratamento (p=0,051) ou a tratamento multimodal com cirurgia e quimioterapia (p=0,095). Mais frequentemente o meningioma foi rostrotentorial (61,2%, n=30) (p=0,116), mais associado à apresentação de crises epiletiformes (p<0,001) e exame neurológico sem alterações significativas (p=0,023). A síndrome vestibular (p=0,002), a dor neuropática (p=0,041) e os problemas na marcha (p=0,006) resultam mais provavelmente da presença de um meningioma infratentorial. Cães com meningioma intracraniano sem problemas na marcha e défices propriocetivos sobreviveram significativamente mais tempo (p=0,020), sendo que para p<0,01, a localização infratentorial (p=0,084) e presença de problemas na marcha (p=0,020) estão associadas a uma maior probabilidade de morrer a qualquer instante. A administração de quimioterapia adjuvante à cirurgia para o tratamento de meningioma intracraniano canino parece vantajosa. Adicionalmente, é possível que a associação de quimioterapia ao tratamento paliativo aumente a eficácia do protocolo farmacológico. Localização infratentorial e manifestação de problemas na marcha e/ou défices propriocetivos podem conferir um pior prognóstico em cães com meningioma intracraniano presuntivo.
ABSTRACT - Survival Analysis after Canine Intracranial Meningioma Diagnosis and its Relationship with Neurologic Signs, Tumor Location and Followed Treatment - For survival analysis of dogs with canine intracranial meningioma as a function of applied treatment, and evaluation of neurological signs and tumor localization as possible prognostic factors, a retrospective study was conducted including 49 dogs with presumptive (n=42) or definitive (n=7) diagnosis of intracranial meningioma, grouped according to followed treatment: medical (n=38) - palliative (n=32) or chemotherapy (n=6) – and surgical (n=11) – surgery (n=7) or surgery and chemotherapy (n=4). Median survival time (MST) for palliative treatment group was 147 days (4.9 months), and 129 days (4,3 months) when only surgery was performed. With a positive effect on survival time of dogs with intracranial meningioma, the administration of chemotherapy alone or in combination with surgery resulted in 360 days (11.8 months) and 468 days (15.6 months) MST, respectively. There was no difference between the survival time distribution curves of each treatment group (p=0.156). However, for p<0.1, dogs with presumptive intracranial meningioma included in the palliative treatment group were about 1.926 and 2.832 times more likely to die at any point of time than if included in another treatment group (p=0.051) or multimodal treatment with surgery and chemotherapy group (p=0.095). More often, meningioma was rostrotentorial (61.2%, n=30) (p=0.116), more associated with the seizures (p<0.001) and normal neurological examination (p=0.023). Vestibular syndrome (p=0.002), neuropathic pain (p=0.041) and impaired gait (p=0.006) are more likely to result from the presence of an infratentorial meningioma. Dogs with intracranial meningioma without impaired gait and propriocetive deficits survived significantly more (p=0.020), and for p<0.01, infratentorial location (p=0.084) and impaired gait (p=0.020) were associated with a higher probability of dying at any moment. Surgical intervention followed by chemotherapy administration seems advantageous for the treatment of canine intracranial meningioma. Additionally, it may be possible that chemotherapy in combination with palliative treatment increases medical treatment effectiveness. Infratentorial localization and impaired gait and/or propriocetive deficits may indicate worse prognosis in dogs with presumptive intracranial meningioma.
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Quach, Pauline. "Lifestyle Risk Factors Associated with Adult Primary Brain Tumours: Quality Assessment of Existing Systematic Reviews, Followed by Updated Analyses and De-Novo Syntheses." Thèse, Université d'Ottawa / University of Ottawa, 2013. http://hdl.handle.net/10393/26243.
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Background: A compilation of high quality systematic reviews (SRs) on lifestyle factors associated with adult glioma and meningioma was developed.
Methods and Materials: Phase 1 consisted of a systematic overview of existing SRs. For Phase 2, high quality SRs were incorporated in an update. Moderate or low quality SRs which had not been considered in a high quality review were eligible for a de-novo synthesis.
Results: Phase 1 resulted in seven moderate to low quality reviews. From this, in Phase 2, smoking, mobile phone and hair dye use were subjected to de-novo reviews. For smoking, it was suggestive that past smokers had an increased risk. For mobile phone use, there was no overall association, however it was suggestive that ipsilateral and high cumulative call time were associated with slight increased risk. No association was observed for personal hair dye use.
Conclusions: Despite these null associations, rigorous SR methods were used providing confidence in conveying these results.
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FOLACCI, JEAN-LUC. "Les metastases des cancers visceraux dans les tumeurs benignes intra-craniennes : a propos d'une metastase d'un cancer thyroidien dans un meningiome intracranien." Nice, 1988. http://www.theses.fr/1988NICE6560.
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Lyons, Rimmer Jade. "The potential of CRL4-DCAF1 and KSR1 as therapeutic targets in low-grade Merlin-deficient tumours." Thesis, University of Plymouth, 2018. http://hdl.handle.net/10026.1/12833.
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Merlin is a tumour suppressor protein that is frequently mutated or downregulated in cancer. Biallelic Merlin inactivation is causative of tumour formation, including schwannoma, meningioma and ependymoma. These tumours can occur sporadically or as part of the genetic condition Neurofibromatosis type 2 (NF2) and cause significant morbidity. The current treatment options are restricted to surgery and radiotherapy, which are invasive and may cause further tumour development. The activity of both the E3 ubiquitin ligase complex Cullin 4 really interesting new gene (RING) E3 ubiquitin ligase- DNA damage binding protein (DDB1) and Cullin 4 associated factor 1 (CRL4-DCAF1) and Kinase suppressor of RAS 1 (KSR1) have been shown to be upregulated in schwannoma to drive tumour growth. KSR1 has also been shown to interact with components of the CRL4-DCAF1 complex. We investigated the expression, interaction and therapeutic potential of targeting these proteins in Merlin deficient schwannoma and meningioma using a primary human cell model and relevant cell lines. We found that DCAF1 and KSR1 protein were overexpressed in schwannoma and meningioma and confirmed that targeting both DCAF1 and KSR1 in meningioma had additive effects on proliferation. We also identified that CRL4-DCAF1 facilitates KSR1 dependent RAF/Mitogen-activated protein kinase (MAPK)/ Extracellular signal regulated kinase (ERK) kinase (MEK)/ERK pathway activity. We showed MLN3651, a neddylation inhibitor that targets ubiquitin ligase activity, reduced proliferation and activated apoptosis in Merlin-deficient tumours. We also showed that Merlin-positive tumours were less sensitive to MLN3651 than Merlin-deficient tumours; therefore, MLN3651 sensitivity may be CRL4-DCAF1-dependent. Finally, combination of MLN3651 and the MEK1/2 inhibitor AZD6244 had additive effects, particularly in meningioma. Combinatorial therapy activated the Hippo pathway, inhibited RAF/MEK/ERK pathway activity and proliferation demonstrating that targeting the activity and downstream pathways of both DCAF1 and KSR1 represents an attractive novel therapeutic strategy in Merlin-deficient tumours.
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SILVA, Geanny Pereira da. "Análise de alterações no número de cópias envolvendo os cromossomos 1p e 22 em meningiomas de baixo grau." Universidade Federal do Pará, 2013. http://repositorio.ufpa.br/jspui/handle/2011/8087.
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CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico
Os meningiomas constituem o segundo tipo de tumor primários cerebral mais comum, originando-se nas meninges que revestem o cérebro e a medula espinhal. Possuem crescimento lento, sendo encontrados com maior freqüência no SNC. Na maioria dos casos são benignos, porém há também casos de meningiomas classificados como malignos. No nível citogenético, os meningiomas são os tumores mais bem estudados em humanos, e os resultados demonstraram que as alterações mais frequentes nesse tipo de tumor tem sido a perda de uma cópia do cromossomo 22 e a deleção do braço curto do cromossomo 1. Essas alterações têm sido associadas ao processo de gênese tumoral, por serem características de tumores de baixo grau, principalmente deleções envolvendo o cromossomo 22. Dessa forma, o objetivo do presente trabalho foi analisar a recorrência de alterações no número de cópias (CNAs) envolvendo os cromossomos 1p e 22 em meningiomas de grau I e II, além de averiguar a existência de outros rearranjos recorrentes, por meio da análise genômica comparativa de alta resolução (array-CGH). As amostras analisadas foram provenientes de oito pacientes. Todas as amostras apresentaram ganhos e perdas de diversos segmentos cromossômicos. Com exceção de um caso, todos os outros apresentaram em maior ou menor grau mais deleções do que amplificações. A perda de segmentos localizados em 1p foi observada em todas as amostras analisadas. Algumas CNAs apresentaram recorrência em até seis dos oito casos. O cromossomo 22 apresentou CNAs em todas as amostras, mas a monossomia total só foi observada em duas das oito amostras. A análise global de CNAs em todas as amostras demonstrou que, apesar de alterações em 1p e 22 serem as modificações mais observadas, como o esperado, outras regiões genômicas também se apresentaram modificadas em várias amostras, apontando para um possível envolvimento dessas modificações com o processo de tumorigênese e progressão tumoral. Algumas delas, como alterações nos pares 9, 12 e 17, já foram observadas em outros trabalhos e foram correlacionadas com meningiomas atípicos e anaplásicos. Dessa forma, os dados obtidos apontam para a existência de um número maior de alterações genômicas em meningiomas de baixo grau, refutando, em parte, a afirmação de que esses tumores são caracterizados por um pequeno número de alterações quando comparados com tumores de malignidade maior. No entanto, o fato desses tumores apresentarem as alterações que são clássicas dos meningiomas, mesmo os benignos, como as deleções em 1p e em 22q, pode ser um indício de que estas alterações devem estar ligadas com os eventos iniciais destes meningiomas, como já foi sugerido diversas vezes por outros autores. Concluindo, essas alterações permanecem como marcadores importantes em meningiomas, e as relações dessas e outras CNAs com a resposta a diferentes tratamentos e ocorrência de recidivas devem ser o próximo passo após a caracterização citogenômica baseada em array-CGH.
Meningiomas are the second most common type of primary brain tumor, originating in the meninges covering the brain and spinal cord. They show slow growth, and are found more often in the CNS, being benign in most case, although there are also cases of meningiomas classified as malignant. At the cytogenetic level, meningiomas are the most well studied tumors in humans: studies in CNS tumors have shown that most cases had chromosomal abnormalities, and the most common alterations in theis type of tumor are the loss of one copy of chromosome 22 and deletion of the short arm of chromosome 1. These alterations have been associated with the tumorigenesis process, because they are found mostly in low-grade tumors, particularly deletions involving chromosome 22. Thus, the aim of this study was to analyze the occurrence of copy number alterations (CNAs) involving chromosomes 1p and 22 meningiomas grade I and II, and in addition to verifying the existence of other recurrent rearrangements through the application of high resolution comparative genomic hybridization (array - CGH ). Tumor samples were collected from eight patients. All samples showed gains and losses of various chromosomal segments. Except for one case, all others showed, in different degrees though, more deletions than amplifications. Loss of 1p segments was observed in all samples. Some CNAs were recurrent, being found up to six out of the eight cases. Pair 22 showed CNV in all samples, but the total monosomy was observed in only two of the eight samples. The global analysis of CNAs in all samples showed that, although changes 1p and 22 were the most frequent observed alterations, as expected, other genomic regions had also alterations in various samples, indicating a possible involvement of these modifications in the process of tumorigenesis and tumor progression. For instance, alterations in pairs 9, 12 and 17, have been observed in other studies and were correlated with atypical and anaplastic meningiomas. Our data indicate the existence of a larger number of genomic alterations in low-grade meningiomas, disagreeing partly with the assumption that these tumors are characterized by a small number of changes, usually involving pair 22 and, less frquently, loss of 1p. However, the fact that these tumors present alterations that are classically found in meningiomas, even benign, such as deletions in 1p and 22q, may be an indication that these changes must be linked with the early events of origin in meningiomas, as already suggested several times by other authors . In conclusion, these alterations remain important markers in meningiomas, and the relationships of these and other CNAs with the response to different treatments and recurrences should be the next step after cytogenomic characterization based on array-CGH has been completed.
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LOPES, Cleiton Mendes. "Análises dos genes TP53, PTEN, IDH1 e IDH2 em tumores não gliais do sistema nervoso humano." Universidade Federal do Pará, 2016. http://repositorio.ufpa.br/jspui/handle/2011/8059.
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Apesar da considerável incidência, estudos de alterações genéticas nos genes TP53, PTEN, IDH1 e IDH2, em tumores não gliais, são raros e, em alguns casos, inexistentes. Os tumores não gliais são classificados geralmente como benignos e raramente evoluem à malignidade, apresentando diferentes classificações, incidências e localizações. Os genes supressores tumorais e de resposta a danos ao DNA, TP53 e PTEN, estão entre os genes mais frequentemente mutados em tumores humanos. Os genes IDH1 e IDH2 estão envolvidos no metabolismo celular e, também, foram encontrados frequentemente mutados em gliomas, melanomas e leucemias, sendo atualmente considerados como bons marcadores em gliomas. Foram realizadas análises de alterações genéticas nos genes citados, a fim de verificar se estão associados à etiologia e/ou progressão de tumores não gliais do Sistema Nervoso Humano (SNH). Foram utilizadas as técnicas de PCR-SSCP para amplificação da região de interesse e triagem mutacional das amostras para posterior sequenciamento. Foram analisadas 37 amostras de tumores não gliais (14 schwannomas, 3 Meningiomas, 4 Meduloblastomas, 2 Neurocitomas e 14 Metástases do Sistema Nervoso Central (SNC). Somente o gene IDH1 apresentou polimorfismos na SSCP em 12 (32,4%) amostras, sendo, então, submetidas ao sequenciamento. No entanto, as reações de sequenciamento foram satisfatórias em apenas em 5 amostras, entre as polimórficas, (1 metástase, 1 meningioma e 3 schwanomas,). Análises dessas 5 amostras identificaram diferentes mutações, uma delas, presente em todas, uma transversão T→A no éxon 4 do códon 106 do gene IDH1, resultando na substituição do aminoácido treonina por serina. Foram, também, identificadas outras mutações em regiões não codificantes (íntron 4) do gene IDH1 em duas dessas amostras. As mutações encontradas em nosso estudo ainda não haviam sido relatadas na literatura. Nossos resultados indicam a participação do gene IDH1 na patogênese desses tumores.
Despite the considerable incidence, studies of genetic changes in gene TP53, PTEN, IDH2 and IDH1, in not glial tumors are rare and, in some cases, nonexistent. Glial tumors are usually not classified as benign and rarely evolve to malignancy, with different classifications, effects and locations. The tumor suppressor genes and response to DNA damage, TP53 and PTEN are among the most commonly mutated gene in human tumors. The genes IDH1 and IDH2 are involved in cell metabolism and also were frequently found mutated in gliomas, melanomas and leukemias, currently being considered as good markers for gliomas. Genetic analyzes were performed in those genes, in order to verify that are associated with the etiology and/or progression of non-glial tumors of Human Nervous System (HNS). SSCPPCR techniques for the amplification of the region of interest and mutational screening of samples for subsequent sequencing were used. We analyzed 37 samples of non-glial tumors (14 schwannomas, meningiomas 3, 4 Medulloblastomas, 2 neurocytomas and 14 metastases of Central Nervous System (CNS). Only the gene IDH1 polymorphisms presented on the SSCP 12 (32.4%) samples, and then subjected to sequencing. However, sequencing reactions were satisfactory in only 5 samples, of the polymorphic, (1 metastasis, meningioma 1 and 3 schwannomas). Analysis of these samples have identified 5 different mutations, one present in all, one transversion T → A in codon 106 of exon 4 of the IDH1 gene resulting in amino acid substitution of threonine by serine. Were also identified other mutations in noncoding regions (intron 4) of gene IDH1 in two of these samples. The mutations found in our study had not yet been reported in the literature. Our results indicate the participation the gene IDH1 in the pathogenesis of these tumors.
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Mainio, A. (Arja). "Depressive and anxious symptomatology in relation to a primary brain tumor:prospective study of neurosurgical patients in Northern Finland." Doctoral thesis, University of Oulu, 2005. http://urn.fi/urn:isbn:9514277163.
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Abstract
The findings on depression and anxiety among brain tumor patients have so far been based on case series and case samples. In Finland, psychiatric research in relation to psychiatric symptoms among patients with different types of brain tumors is lacking.
The study population of this thesis consisted of 101 patients (39 males and 62 females) aged between 20 and 82 years with a solitary primary brain tumor treated surgically at the Oulu Clinic for Neurosurgery, Oulu University Hospital between February 1990 and March 1992. The major histological subgroup consisted of gliomas (40%), and the rest were meningiomas (33%), acoustic neurinomas (13%), pituitary adenomas (8%) and other types (6%).
The psychiatric symptoms of the patients were assessed at three time points, namely before tumor operation as well as at three months and at one year after operation by two valid measurement instruments, the Beck Depression Inventory and the Crown Crisp Experiential Index. In addition, the patients' functional state was evaluated by the Karnofsky Performance Scale and their quality of life according to Sintonen 15 D.
Prevalence of at least mild depression before tumor operation was 30% for males and 38% for females. The mean depressive scores decreased significantly for up to one-year during follow-up for both males and females, but they remained notably high in all patients. Decreased functional status (KPS under 70) in the patients was significantly associated with high depressive scores at all measurement points. The decrease in the mean depressive scores was significant among patients with an anterior tumor and those with a pituitary adenoma.
Five-year survival of the brain tumor patients was found to be mainly associated with the histology of the tumor. Survival time in months (SD) of the patients with high-grade (III–IV) gliomas was shown to be 22.5 (21.4), while it was 50.2 (19.9) for the patients with low-grade (I–II) gliomas, and 58.2 (9.4) for the rest of the patients. Depression among low-grade glioma patients was significantly associated with worse survival at five years follow-up.
The level of anxiety was shown to be significantly higher among patients with a primary brain tumor in the right hemisphere compared to the anxiety scores among patients with left hemispheric tumors. A significant increase was found in the level of obsessionality over time in the female patients with a brain tumor in the left anterior location of the brain at three months after operation.
The level of quality of life (QOL) was significantly worse among female brain tumor patients compared to males. Depressive females had significantly lower quality of life compared to that of non-depressive females up to one-year follow-up after surgical operation of the tumor.
Depression, anxiety and obsessive-compulsive symptoms have to be recognized and be treated by psychotherapy and pharmacotherapy as soon as possible at every unit where brain tumor patients are followed and encountered.
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Chakrama, Fatima Zahra. "La protéine Gec1/Gabarapl1 : rôle au cours de l'autophagie et expression dans les cellules cancéreuses." Thesis, Besançon, 2011. http://www.theses.fr/2011BESA3007/document.
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Le gène Gec1/Gabarapl1 a été identifié au sein de notre laboratoire comme un gène régulé par les estrogènes. Il appartient à la famille Gabarap incluant les gènes Gabarap, gabarap/2 et Gabarapl3 qui codent des protéines présentant de fortes homologies de séquences. L'étude fonctionnelle de Gabarapl 1 a montré que cette protéine est impliquée dans le transport des récepteurs et particulièrement les récepteurs Gabaₐ et des κ-opioïdes via son interaction avec la tubuline et la protéine NSF. Cependant, il a été décrit que certaines protéines de la famille Atg8 sont impliquées dans l' autophagie, un mécanisme de dégradation et de survie cellulaire, qui se caractérise par la formation de doubles membranes appelées autophagosomes. Les objectifs de mon travail étaient, d'une part, de caractériser le rôle de la protéine GABARAPL1 au cours de !'autophagie et, d'autre part, de caractériser son expression dans des lignées et tissus cancéreux et sa régulation en réponse à des composés anti-cancéreux. Tout d'abord, nous avons montré que Gabarapl1 est clivée par la protéase Atg4B au niveau de sa glycine 116 avant sa conjugaison à des phopholipides. Cette forme modifiée, lipidée, est localisée à la surface des autophagosomes et des lysosomes. Nous avons ensuite montré que Gabarapl1 est faiblement exprimée dans de nombreuses lignées cancéreuses, que son expression est altérée dans les méningiomes et qu'elle est régulée par des inhibiteurs du protéasome. Ces travaux ont montré, pour la première fois, que la protéine Gabarapl1 est associée à des vésicules autophagiques et permettront de poser les hypothèses de nos futurs travauxThe Gec1 / Gabarapl1 gene was identified in our laboratory as an early estrogen regulated gene. Gabarapl1 belongs to the Gabarap family, also including Gabarap, Gabarapl2 and Gabarapl3 genes, that encode proteins which present high sequence homology with each other. A functional study of the Gabarapl 1 protein showed that this protein is involved in the transport of receptors such as the Gabaₐ and κ-opioid receptors via its interaction with tubulin and NSF. It has been reported that the Atg8 family proteins are involved in autophagy, a mechanism of degradation and cell survival that is charactenzed by the formation of double membranes called autophagosomes. The aims of my research were, firstly, to characterize the role of the Gabarapl1 protein during autophagy and, secondly, to study its expression in cancer cell lines and cancerous tissues and its regulation in response to anti-cancer drugs. First, we showed that Gabarapl1 is cleaved in the cells by the protease Atg4B at its 116 glycine residue prior to its conjugation to phospholipids. This modified form, lipidated, is located on the surface of autophagosomes and lysosomes. We then showed that Gabarapl1 expression is reduced in many cancer cell lines, and that its expression is also altered in meningiomas. Finally, we showed that Gabarapl1 expression is regulated by proteasom€: inhibitors. Thus, our results demonstrated for the first time that the Gabarapl1 protein is associatec with autophagie vesicles and allow us to propose hypothesis for future work
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Graillon, Thomas. "Etudes des voies somatostatinergiques et Pi3Kinase-Akt-mTOR dans les tumeurs intra-crâniennes (Adénomes hypophysaires, Méningiomes, Chordomes)." Thesis, Aix-Marseille, 2014. http://www.theses.fr/2014AIXM5053.
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1. Adénomes hypophysaires somatotropes : Elaboration d'un modèle in vitro et in vivo d'études du récepteur SST2 et des voies de signalisation somatostatinergiques.Afin de préciser l'étude du récepteur SST2, nous avons mis en place un modèle d'étude in vitro et in vivo, en établissant une lignée polyclonale exprimant le récepteur SST2 humain à de hauts niveaux. Ce modèle nous permettra de tester de nouveaux agonistes somatostatinergiques comme le pasiréotide et d'étudier de façon approfondie les voies de signalisation.2. Méningiomes : Mise en place d'un modèle de culture primaire de méningiome in vitro et étude de l'effet de l'octréotide, du pasiréotide et de l'everolimus sur la prolifération cellulaire et les voies de signalisation intracellulaire.Etant donné la forte expression du récepteur SST2, nous avons démontré in vitro un effet anti-prolifératif de l'octréotide sur les cellules de méningiomes via une inhibition de la voie Pi3kinase-Akt-mTOR. L'octréotide a significativement amélioré l'inhibition par l'everolimus de la prolifération cellulaire.Un effet additif des 2 drogues a été observé. Ces résultats ont permis la mise en place d'une étude clinique . Par ailleurs, on observe un meilleur effet du pasiréotide comparé à celui de l'octréotide.3. Chordomes : Mise au point d'un modèle de culture primaire de cellules de chordomes in vitro et études préliminaires.Les premiers résultats avec octréotide, pasiréotide et everolimus sont concluants, mettant en évidence une diminution de la prolifération cellulaire, et nous incitent à poursuivre les investigations1.Somatotroph adenomas : Development of an in vitro and in vivo model to study SST2 receptor and somatostatin pathway.To precise SST2 role in tumorigenesis, we developed an in vitro and in vivo model, using a polyclonal cell line with high and stable SST2 expression level. This model will provide to test new somatostatin agonists as pasireotide and further studies on intracellular pathway in ''somatotroph'' context.2. Meningiomas : Development of a model of meningioma primary culture in vitro with study of octreotide, pasireoide and everolimus effects on cell proliferation and intracellular pathways. Given the strong SST2 expression, we demonstrated an in vitro antiproliferative effect of octreotide on meningioma cells via an inhibition of Pi3kinase-Akt-mTOR pathway.In vitro, we observed that octreotide significantly improved everolimus induced cell proliferation inhibition. An additive effect of the 2 drugs was observed in each tested tumor. These results supported the development of a clinical trial. Pasireotide provided a better effect than octreotide, alone or in combination with everolimus on cell proliferation and intracellular pathways.3. Chordomas : Development of an in vitro model of chordoma cell primary culture with preliminary studies.We developed a model of in vitro chordoma cell culture. This model is reliable and stable, providing study of different drugs. SST2 receptor expression was lower than in meningiomas but SST2 expression remained significant in the majority of the tumors. First results with octreotide, pasireotide and everolimus are relevant, with a decrease in cell proliferation leading to further studies
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Ando, H., A. Natsume, T. Senga, R. Watanabe, I. Ito, M. Ohno, K. Iwami, et al. "Peptide-based inhibition of the HOXA9/PBX interaction retards the growth of human meningioma." 2013. http://hdl.handle.net/10454/10104.
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noBackground Meningiomas are the most common type of intracranial tumor, accounting for between 24 and 30 % of primary intracranial tumors. Thus far, no biomarkers exist to reliably predict the clinical outcome of meningiomas. A previous genome-wide methylation analysis revealed that HOXA9 is one of the most functionally relevant biomarkers. In this study, we have examined whether HOXA9 is a potential therapeutic target in meningiomas, using HXR9, a peptide inhibitor of the interaction between HOXA9 and its cofactor PBX. Methods We determined the expression level of HOXA9 in human meningiomas, meningioma cell lines, and normal brain tissue. Meningioma in culture and in subcutaneous tumors was treated with HXR9. We also examined the disruption of HOXA9/PBX dimers. Results We first confirmed that HOXA9 is highly expressed in meningiomas, but not in normal brain tissue. The HXR9 peptide blocks the binding of HOXA9 to PBX, leading to an alteration of DNA binding, and subsequent regulation of their target genes. HXR9 markedly inhibited the growth of meningioma cells and subcutaneous meningeal tumors. Conclusion There is no effective chemotherapy for meningiomas at present, and targeting the HOXA9/PBX interaction may represent a novel treatment option for this disease.
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Magalhães, Tomás Rodrigues. "Efeito da radioterapia no tratamento de tumores intracranianos no cão: meningiomas e gliomas." Master's thesis, 2016. http://hdl.handle.net/10348/7713.
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Dissertação de Mestrado Integrado em Medicina VeterináriaA radioterapia tem sido considerada a terapia de eleição para vários tumores cerebrais no cão, nomeadamente o glioma e o meningioma intracraniano. Após ter sido realizada uma revisão acerca da técnica e dos dois tipos de tumor, em particular, procedeu-se à realização de um estudo de caráter retrospetivo, com dados relativos a doentes tratados no hospital VRCC - Veterinary Referrals, no Reino Unido. Os objetivos definidos foram avaliar a eficácia desta abordagem terapêutica e procurar estabelecer associações entre várias características epidemiológicas, clínicas, diagnósticas e terapêuticas com o tipo tumoral e os tempos de sobrevivência apresentados. Assim, foram incluídos 32 cães com diagnóstico de glioma ou meningioma intracraniano, tratados com radioterapia, cujos relatórios clínicos foram analisados. Procedeu-se, ainda, ao cálculo de dois tempos de sobrevivência: o total (TST) e o pós-tratamento (TSPT), que se assumiram desde o diagnóstico ou do fim da radioterapia, respetivamente, até à morte ou final do período de estudo. Apenas 30 doentes foram considerados para os cálculos de sobrevida. O sexo e o realce pós-contraste exibiram associações estatisticamente significativas (P<0.05) com o diagnóstico tumoral. Estes resultados traduziram-se numa predisposição sexual dos machos para o tipo glial e das fêmeas para o tipo meningeal e numa maior especificidade do realce pós-contraste, observado na ressonância magnética, para o meningioma. Verificou-se, ainda, que, apenas, a raça e o sexo se assumiram como fatores de prognóstico, tendo estado associados significativamente (P<0.05) com os tempos de sobrevivência. Ser da raça boxer ou labrador retriever, bem como ser fêmea constituem, assim, um benefício na sobrevida destes doentes. Os valores medianos obtidos foram de 372 dias para o TSPT e de 446.5 dias para o TST, em termos globais. As taxas de sobrevida ao final de 1 e 2 anos foram, respetivamente, de 50% e 23.3%. A radioterapia é, assim, uma metodologia de tratamento eficaz nestes quadros neoplásicos, apresentando resultados superiores a outras abordagens terapêuticas.
Radiation therapy has been considered the treatment of choice for many brain tumors in dogs, like glioma and intracranial meningioma. After a review about the technique and these two types of tumor, in particular, a retrospective study was carried out, with the informations of patients treated in the hospital VRCC - Veterinary Referrals, in United Kingdom. The goals were set to evaluate the efficacy of this therapeutic approach and to search associations between different epidemiological, clinical, diagnostic and therapeutic features with the tumor type and the survival times. This study included 32 dogs diagnosed with glioma and intracranial meningioma which undergone radiation therapy. The clinical reports were analyzed. Two survival times were calculated: overall (OST) and post-treatment (PTST), from the diagnosis or the end of the radiation, respectively, until death or end of the study period. Only 30 patientes were considered for these survival calculations. Sex and contrast enhancement exhibited statistically significant associations (P<0.05) with tumor diagnosis. These results showed a sexual predisposition of males for glial type and females for meningeal type and a greater specificity of contrast enhancement, observed on MRI, for meningioma. It was found that just the breed and the sex are prognostic factors, as they were significantly associated (P<0.05) with survival times. Boxer and labrador retriever breeds and the female sex were considered as a survival benefit in these patients. Median values were 372 days for TSPT and 446.5 days for the TST. The 1- and 2-year survival rates were, respectively, 50% and 23.3%. Thus, radiation therapy is an effective treatment option for these neoplastic cases, with better results than other therapeutic approaches.
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Chuan-Fu and 黃全福. "Diffusion Magnetic Resonance Imaging in the Evaluation of the Response of Meningioma and Metastatic Brain Tumor Treated by Gamma Knife Radiosurgery." Thesis, 2009. http://ndltd.ncl.edu.tw/handle/63379861568281181930.
Full textAbstract:
博士中山醫學大學
醫學研究所
97
Background: Patients usually receive serial magnetic resonance imaging (MRI) examinations to assess stereotactic radiosurgery (SRS) effects by volume change. But loss of tumor cell after radiosurgical treatment results in a relative increase in extracellular space and may lead to alteration of apparent diffusion constant (ADC). Our hypothesis is to investigate if the ADC can be used, rather than with methods depending on changes in tumor size, to predict treatment success after treatment of meningioma and brain metastases with SRS. Methods: We conducted a prospective trial involving 6 patients with intracranial meningiomas and 21 patients with 32 solid or solid-dominated lesions treated by SRS with 201-source cobalt in our Gamma Knife center. Patients received complete diffusion MRI before treatment and at multiple intervals following SRS. We followed up MRI findings and clinical outcomes at 3 months, and thereafter in 3-month intervals. We detected the long-term results of diffusion MRI in 7 patients treated for at least 5 years. We calculated apparent diffusion coefficients (ADC) from echoplanar diffusion weighted imaging, and compared mean ADC values. Mean ADC values at the various time intervals were compared with each other to see whether or not the ADC might be used as an early indicator of treatment success or failure. Results: The ADC for meningioma was 0.55-0.64 x 10-3 mm2/s (mean ± SD). We observed 2 ADC phase changes after SRS: a significant (p < 0.05) reduction phase beginning at 4 hours and lasting 4 days after SRS followed by an elevation phase to pseudonormalized values. ADC significantly increased 30 days after SRS, reaching a plateau in 3 months. MRI follow-up at 3-month intervals showed stable tumor size in all patients, with 3 patients revealing evidence of tumor necrosis. The ADC value for the long-term group was 1.26 x 10-3 mm2/s. (p < 0.05); however, MRI follow-up showed tumor shrinkage in 3 patients. The mean pre-treatment value of the ADC in the metastatic tumors was 1.05 ± 0.12 x10-3 mm2/s. This value for the tumors rose significantly (P=0.009) seven days after SRS and continued to rise with time. Magnetic resonance imaging (MRI) showed that 91% of these tumors had been controlled by the SRS. ADC values in cystic/necrotic tumor tissue (2.13 ± 0.18 x 10-3 mm2/s) were significantly (P<0.001) higher than in non-central necrotic tumor tissue (1.61 ± 0.14 x 10-3 mm2/s). Conclusion: Gamma knife treatment is efficacious for meningioma and metastatic brain tumors. Serial changes in ADC values might eventually be useful to evaluate treatment success and in some patients even detected at early time points, and to distinguish radiation-induced central necrosis from tumor re-growth in cases where other imagery is not definitive.