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MONTEIRO, Márcia Lima de Azevedo. "Comportamento biológico dos meningiomas: um estudo de 868 casos." Universidade Federal de Pernambuco, 2011. https://repositorio.ufpe.br/handle/123456789/20120.
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Monteiro MLA. Comportamento biológico dos meningiomas: um estudo de 868 casos. [Tese de Doutorado]. Recife: Universidade Federal de Pernambuco; 2011.Introdução:Meningiomas são neoplasias, em sua maioria, de apresentação benigna. Podem, no entanto,apresentar recidiva mesmo após remoção radical. A caracterização de meningiomas e o conhecimento de fatores relacionados à recidiva é imprescindível, devido a sua prevalência, importância clínica e às possibilidades de cura através de remoção cirúrgica. Objetivos:Caracterizar meningiomas do ponto de vista clínico-patológico e de fatores relacionados a seu tratamento cirúrgico e contribuir para o conhecimento de seu comportamento biológico; determinar a prevalência de recidiva demeningiomas e verificar a influência de determinados fatores sobre a recidiva.Material e Métodos:Foram analisados 868 casos de pacientes submetidos à remoção cirúrgica de meningiomas no Hospital Nordstadt, Hannover, Alemanha, de 1978 a 1994, para gênero, distribuição etária, associação a neurofibromatose, multiplicidade, tipo e grau histológico, localização, características de crescimento do tumor e recidiva. Para análise dos resultados foram obtidas distribuições de frequências, teste 2de igualdade de proporções ao nível de 5,0% e intervalo de confiança de 95,0% para a prevalência de recidiva. Resultados:A idade dos pacientes variou de 7 a 85 anos, média e desvio padrão de 53,46 e 13,89 anos, respectivamente. Da 5aà 7adécadas, concentraram-se 71,7% dos pacientes. A distribuição por gênero foi de 74,0% femininos e 26,0% masculinos. Meningiomas clássicos representaram 94,2% do total; atípicos, 3,8%; e anaplásicos, 1,9%. Em 824 casos, 89,1% eram intracranianos (65,9% basais); 8,5%, espinhais; e 2,4%, crânio-cervicais. A ocorrência associada a neurofibromatose foi de 4,9%; e a multiplicidade, de 6,7%. Aos tumores globoides (84,6%), seguiram-os em placa (6,7%) e os intraósseos (2,4%). Cápsula foi observada em 74,5% dos casos. A remoção foi total em 79,6%. A prevalência de recidivas foi de 16.9% (14,2% a 19,5%) com 95,0% de confiança. O tempo médio entre as recidivas tendeu a diminuir: de 5,68 anos entre a 1aremoção e 1arecidiva para 0,90 anos entre a 3ae a 4arecidivas.Em 785 casos, o percentual de recidiva foi de 2,7% em dois anos; 7,2% em 5 anos; 13,1% em 10 anos; 16,3% em 15 e 16,9% em 20 anos. O percentual de recorrência foi mais elevado no gênero masculino (22,1% x 15,1%); aumentou nas 4 primeiras décadas de vida e decresceu da 5aà 9adécadas; foi menor entre os pacientes acima de 65 anos (3,0% x 20,5%); mais elevado entre os de grau III (71,4%), seguido do grau II (51,7%) e do grau I (15,1%). Percentuais mais elevados de recidiva foram encontrados entre tumores removidos parcialmente (32,7% x 11,5%); entre pacientes portadores de neurofibromatose (38,5% x 15,7%); dentre os múltiplos (34,6% x 15,5%); na presença de infiltração dural (19,6% x 13,1%), óssea (23,6% x 12,9%) e muscular (57,9% x 15,8%); e entre os não capsulados (20,7% x 8,2%). A associação da recidiva foi significativa com gênero, faixa etária, tipo e grau histológico, extensão da remoção, neurofibromatose, multiplicidade, tipo de crescimento, infiltração dural, óssea ou muscular e presença de cápsula com valores de P=0,022 para gênero, P= 0,017 para infiltração dural e P<0,001 para as demais variáveis. Para outras variáveis analisadas não se comprovou associação significativa com a recidiva. Conclusão: Dos resultados se conclui que osmeningiomas são mais frequentes em mulheres, entre a 5ae a 7a décadas de vida; a maioria é do tipo clássico, grau I, globóide, capsulada; a localização intracraniana é cerca de 10 vezes mais frequente que a espinhal; a base do crânio é uma localização frequente; a remoção total é possível para a maioria dos casos; um percentual considerável recidivou, 16,9% e a taxa de recidiva aumentou com o tempo de seguimento. A recidiva é influenciada por gênero, faixa etária, tipo e grau histológico, extensão da remoção, neurofibromatose, multiplicidade, tipo de crescimento, infiltração dural, óssea ou muscular e presença de cápsula.
Monteiro MLA. Studyonthe biological behaviorof meningiomas, an analisis of 868 cases.[PhD Thesis]. Recife. Pernambuco. Brazil:Federal University of Pernambuco; 2011.Introduction:Meningiomas are neoplasias of benign presentation in their majority. However, they can present relapse even after radical removal.The characterization of this neoplasms and knowledge of the factors relating to the surgical treatment and the search for factors related to recurrence of meningiomas is imperative, due to its prevalence, clinical importance and possibility for cure. Objective:To characterize meningiomas from a clinical-pathological point of view and the factors relating to its surgical treatment and to contribute to knowledge of its biological behavior; to determine the prevalence of relapse in meningiomas and to verify the influence of certain factors in relapse.Material and Methods:868 cases of patients subjected to the surgical removal of meningiomas at Nordstadt Hospital, Hanover, Germany, between 1978 and 1994 were analyzed for gender, age distribution, association with neurofibromatosis, multiplicity, histological type and degree, location, tumor growth characteristics and relapse. For analysis of the results, frequency distributions, c2proportional equivalence test at a level of 5.0% with a confidence interval of 95.0% for the prevalence of relapse were obtained. Results: Patient age varied from 7 to 85 years, an average and standard deviation of 53.46 and 13.89 years, respectively. 71.7% of the patients were concentrated in the 50-70 age group. Gender distribution was 74.0% female and 26.0% male. Classic meningiomas represented 94.2% of the total; atypical, 3.8%; and anaplasic, 1.9%. Of 824 cases, 89.1% were intracranial (65.9%, basal); 8.5%, spinal; and 2.4%, cranial-cervical. Association with neurofibromatosis was 4.9%; and multiplicity, 6.7%. Globoid tumors (84.6%) were followed by those en placa(6.7%) and intraosseous (2.4%). Capsulation was observed in 74.5% of the cases. Removal was total in 79.6%. The prevalence of relapse was 16.9% (14.2% to 19.5%) at 95.0% confidence. The average time between relapses tended to decrease: from 5.68 years between the first removal and the first relapse to 0.90 years between the third and fourth relapses. . In 785 cases, the percentage of relapses was 2.7% within two years; 7.2% within 5 years; 13.1% within 10 years; 16.3% within 15 years and 16.9% within 20 years. The percentage for relapse was higher in the male gender (22.1% x 15.1%); increasing in the first four decades of life and decreasing in the fifth to ninth decades; it was lower in patients over 65 years of age (3.0% x 20.5%); higher in those of degree III (71.4%), following by degree II (51.7%) and by degree I (15.1%). A higher percentage of relapse was found in partially removed tumors (32.7% x 11.5%); in patients with neurofibromatosis (38.5% x 15.7%); in multiples (34.6% x 15.5%); in the presence of dural infiltration (19.6% x 13.1%), bone (23.6% x 12.9%) and muscular (57.0% x 15.8%); and in non-encapsulated (20.7% x 8.2%). The association of relapse was significant with respect to gender, age group, histological type and degree, extent of removal, neurofibromatosis, multiplicity, growth type, dural, bone or muscular infiltration and capsule presence with values of P=0.022 for gender, P=0.017 for dural infiltration and P<0.001 for the other variables. For the other variables analyzed, there was no significant correlation to relapse. Conclusion:From the results, it is concluded that meningiomas are more frequent in women, between 50 and 70 years of age; most are classic in type, degree I, globoid, capsulated; an intracranial is about 10 times more common than a spinal location; the base of the skull is a common location; totalremoval is possible in most cases; a considerable percentage relapsed 16.9% and the recurrence rate increased with time of follow up . The association of relapse was significant with respect to gender, age group, histological type and degree, extent of removal, neurofibromatosis, multiplicity, growth type, dural, bone or muscular infiltration and capsule presence.
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Suárez, Alvarado Edwin Efraín. "Meningiomas recidivantes postquirúrgicos." Bachelor's thesis, Universidad Nacional Mayor de San Marcos, 2005. https://hdl.handle.net/20.500.12672/2060.
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Objetivo: Identificar los factores relacionados con la recurrencia de los meningiomas intracraneales operados en el Instituto Especializado de Enfermedades Neoplásicas “Eduardo Cáceres Graziani”.
Material y Métodos: Estudio retrospectivo, comparativo, analítico, de caso control. La población de estudio estuvo constituida por los pacientes operados con diagnóstico anatomopatológico de meningioma intracraneal que fueron operados desde el año 1984 a 1997, con control postoperatorio a cinco años.
Resultados: 55 pacientes cumplieron los criterios de inclusión; de estos, 23 (42%) presentaron recurrencia y 32 (58%) no presentaron recurrencia. Se realizó la remoción quirúrgica total en 36 pacientes y subtotal en 19 pacientes. Tuvieron recurrencia el 57.8% de los pacientes con resección quirúrgica subtotal y el 33.3% de pacientes con remoción total; esto nos da un OR de 2,7. con una p< 0.05. Con respecto al sexo, se observó mayor recurrencia del meningioma en pacientes de sexo masculino, con un OR de 1.7. La edad promedio de los pacientes con recurrencia fue de 43.9 ± 16.3 años versus 40. 85 ±17.7 del grupo control. El tiempo de recurrencia fue en promedio de 30.7 ± 16.3 meses. La localización del meningioma que más recurre fue la zona temporal, relacionada con la base de cráneo y con el ala mayor del esfenoides.
El abordaje que presentó mayor recurrencia fue el frontoparietal, mientras que el frontal, parietal, frontoparietotemporal y el temporoparietal tienen menor recurrencia. Con respecto al tipo histológico no existe preponderancia de ningún tipo de meningioma con respecto a la recurrencia.
Conclusiones: El factor más importante relacionado con la recurrencia del meningioma intracraneal operado fue el grado de resección quirúrgica, encontrándose que un paciente sometido a una remoción quirúrgica subtotal tiene 2,7 veces más posibilidades de presentar recurrencia del meningioma en comparación con la resección quirúrgica total.--- Objective: To identify the factors related to the recurrence of meningioma intracraneal patient in the Specialized Institute of Neoplasicas Diseases. “Eduardo Cáceres Graziani”. Material and Methods: Retrospective, comparative, analytical study, of case control. The study population was constituted by patients with intracraneal diagnosis of meningioma patients from year 1984 to 1997, with postoperating control to five years. Results: 55 patients fulfilled the inclusion criteria; of these, 23 (42%) presented recurrence and 32 (58%) did not present recurrence. It was made total the surgical removal in 36 patients and subtotal in 19 patients. The 57,8% of the patients with subtotal surgical removal and the 33,3% of patients with total removal had recurrence; this gives a OR us of 2.7, with p< 0.05.With respect to sex, greater recurrence of meningioma in patients of masculine sex was observed, with a OR of 1.7.The age average of the patients with recurrence is of 43,9 ± 16,3 years versus 40. 85 ±17.7 of the group control. The time of recurrence ± was in average of 30,7 16,3 months. The location of meningioma that resorts more is the temporary zone, related to the base of skull and the greater wing of the esfenoides. The boarding that presents greater recurrence was the frontoparietal, whereas the frontal, parietal, frontoparietotemporal and the temporoparietal have minor recurrence. With respect to the histologic type superiority of any type of meningioma with respect to the recurrence does not exist. Conclusions: The most important factor in the recurrence of meningioma was the degree of surgical resection, being that a patient submissive subtotal a surgical removal has 2.7 times more possibilities of presenting recurrence of meningioma.
Tesis de segunda especialidad
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WADA, KENTARO, TOMOYUKI NODA, KENICHI HATTORI, HIDEKI MAKI, AKIRA KITO, and HIROFUMI OYAMA. "SURGICAL RESULTS OF PARASAGITTAL AND FALX MENINGIOMA." Nagoya University School of Medicine, 2012. http://hdl.handle.net/2237/16041.
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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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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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WADA, KENTARO, TOMOYUKI NODA, KENICHI HATTORI, HIDEKI MAKI, AKIRA KITO, and HIROFUMI OYAMA. "POSTOPERATIVE RECOVERY FROM UNILATERAL BLINDNESS CAUSED BY TUBERCULUM SELLAE MENINGIOMA." Nagoya University School of Medicine, 2012. http://hdl.handle.net/2237/16036.
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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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Okuchi, Sachi. "Grading Meningioma: A Comparative Study of Thallium-SPECT and FDG-PET." Kyoto University, 2016. http://hdl.handle.net/2433/217137.
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Bigatão, Marcela dos Reis. "A capacidade funcional de pacientes submetidos a neurocirurgia oncológica." Universidade de São Paulo, 2010. http://www.teses.usp.br/teses/disponiveis/17/17137/tde-07012016-151915/.
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Introdução: A capacidade funcional refere-se fundamentalmente à potencialidade humana para o desempenho ocupacional, imprescindível para uma melhor qualidade de vida. O objetivo desta pesquisa, aprovada pelo Comitê de Ética em Pesquisa do HCFMRP-USP (processo no 648/2008), foi avaliar a capacidade funcional de pacientes submetidos a neurocirurgia oncológica e sua relação com a qualidade de vida. Método: Durante o período de maio/08 a abril/09 (12 meses) foram avaliados 52 sujeitos adultos de ambos os sexos; o grupo experimental teve 26 pacientes, sendo 14 com diagnóstico de meningioma (grupo1) e 12 com diagnóstico de glioma de alto grau (grupo 2); e o grupo controle teve 26 sujeitos, subdivididos em grupos: 1A (pareado com o grupo 1) e 2A (pareado com grupo 2). Foram realizados dois tipos de dinamometria - avaliação de força de preensão (Grip TrackTM Testing) e de pinça (Pinch TrackTM Testing) com equipamento computadorizado Tracker SystemTM; aplicação de protocolos internacionais validados no Brasil - Hospital Anxiety and Depression Scale HAD, Item Short-Form Health Survey - SF-36 e Health Assessment Questionnaire HAQ, no período pré-operatório e no terceiro mês de pós-operatório. Na análise estatística foram aplicados os testes Mann-Whitney, Wilcoxon e Coeficiente de Correlação de Spearman Resultados: Constatou-se que nos três primeiros meses de pós operatório houve aumento da capacidade funcional dos sujeitos dos grupos experimentais (1 e 2) e diminuição dos sintomas de ansiedade e depressão; não houve diferença significativa nos testes de força no pré e no pós operatório, mas ambos os grupos apresentam diminuição de força no membro dominante em comparação com os grupos controle. Houve correlações de forte magnitude entre os dados coletados através dos testes Grip TrackTM Testing, Pinch TrackTM Testing; protocolos: HAD, HAQ e SF-36, com rho 0,600 a 0,969. Os domínios aspecto social e emocional do instrumento de qualidade de vida mostraram uma piora no pósoperatório imediato. Esses resultados corroboram a compreensão ampliada do conceito de funcionalidade, como proposto na Classificação Internacional de Funcionalidade e Incapacidade e Saúde\" (CIF). Conclusão: A funcionalidade está diretamente relacionada com a qualidade de vida, principalmente nos aspectos psicossociais, sendo necessária compreendê-la de forma mais ampla do que funções físicas específicas, para implementar planos de tratamentos mais adequados para os sujeitos com tumor cerebral, tanto no pré como no pós operatório, com acompanhamento de uma equipe multidisciplinar.Introduction. Functional capacity refers mainly to the potential for human occupational performance, essential for a better quality of life. This research, approved by the Committee of Ethics in Research- HCFMRP USP (in case 648/2008), was to assess the functional capacity of patients undergoing neurosurgery oncology and its relationship to quality of life. Methods. During the period of the abril/09 May/08 (12 months) were assessed 52 subjects adults of both sexes, the experimental group had 26 patients, 14 with a diagnosis of meningioma (group1) and 12 diagnosed with high grade glioma (group 2); and the control group has 26 subjects, divided into groups: 1A (paired with group 1) and 2A (paired with group 2). Were performed two types of dinamometry - evaluation of grip strength (grip TrackTM Testing) and pinch (Pinch TrackTM Testing) SystemTM Tracker with computerized equipment, application of international protocols validated in Brazil - Hospital Anxiety and Depression Scale - HAD, Item Short- Form Health Survey - SF-36 and Health Assessment Questionnaire - HAQ in the preoperative period and in the third month postoperatively. Statistical analysis using the statistical Mann-Whitney, Wilcoxon and Spearman Correlation Coefficient. Results . It was found that the first three months postoperatively increased functional capacity of the subjects of the experimental groups (1 and 2) and decrease symptoms of anxiety and depression, no significant difference in the strength tests before and after surgery but both groups have reduced strength in the dominant limb compared with control groups. There were strong correlations between the magnitude of data collected through tests Grip TrackTM Testing, Testing Pinch TrackTM; protocols: HAD, HAQ and SF-36 with rho 0.600 to 0.969. The aspect of social and emotional domains of quality of life instrument showed a worsening in the immediate postoperative period. These results support the expanded understanding of the concept of functionality, as proposed in the \"International Classification of Functioning and Disability and Health (ICF). Conclusion. The functionality is directly related to the quality of life, especially on psychosocial aspects and needed to understand it more broadly than specific physical functions, to implement plans of treatment best suited to individuals with brain tumor, both pre and postoperatively, with the accompaniment of a multidisciplinary team.
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Junior, Irineu Renzi. "Expressão dos microRNAs miR-1 e miR-133b e dos genes ACVR1C, CCL18, VGLL3, ASPN, OGDHL, BTC em meningiomas com e sem deleção do cromossomo 22q." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/17/17137/tde-23012016-113912/.
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Introdução: Dentre os tumores primários do SNC, o meningioma é o tipo mais frequentemente diagnosticado, sendo responsável por 35,5% dos casos, considerando-se todas as faixas etárias. A gênese dos meningiomas é um processo complexo que envolve o acúmulo de alterações genéticas, sendo o evento mais conhecido a deleção no braço longo do cromossomo 22. O entendimento da iniciação e do crescimento dos meningiomas em nível molecular pode ajudar a definir novos alvos de terapia e, neste contexto, tem se destacado na última década o estudo dos microRNAs (miRNAs). Os miRNAs são uma classe de pequenos RNAs não codificadores que regulam a expressão gênica e têm um papel crucial no desenvolvimento de vários tipos de câncer. O reconhecimento do papel destes RNAs na fisiopatologia dos tumores do SNC vem ganhando destaque. O objetivo deste estudo é compreender o envolvimento da deleção do cromossomo 22q no perfil de expressão de genes e de miRNAs nos meningiomas grau I e, com isso, possibilitar uma melhor compreensão da sua natureza que permita propor alvos potenciais para novas formas de terapia molecular no futuro. Pacientes e métodos: Em um estudo prévio de nosso grupo foi feita uma análise global da expressão gênica pela metodologia de microarrays. Inicialmente para determinação dos grupos foi feita uma análise pela técnica de FISH para identificar quais amostras tinham a deleção do cromossomo 22q e por análise dos microarrays foram selecionados microRNAs e genes para validação PCR em tempo real. Em nosso estudo atual foram utilizadas 15 amostras em cada grupo: um grupo de meningiomas com deleção do cromossomo 22q, um segundo grupo de meningiomas sem deleção do cromossomo 22q e um grupo controle de 15 amostras de aracnoide normal. Os genes selecionados foram o ACVR1C, CCL18, VGLL3, ASPN, OGDHL e BTC e os miRNAs foram o miR-1 e miR-133b. Resultados e Conclusões: Os genes e microRNAs selecionados pela análise de microarray e validados por PCR em tempo real mostraram-se diferentemente expressos entre meningiomas com deleção do cromossomo 22q e meningiomas sem deleção do cromossomo 22q. Os genes ACVR1C, CCL18 e VGLL3 foram hipoexpressos em ambos os grupos de meningiomas, com deleção do cromossomo 22q e sem deleção do cromossomo 22q. O gene ASPN também foi hipoexpresso em meningiomas sem deleção do 22q quando comparado ao grupo controle. O gene OGDHL foi hiperexpresso em meningiomas sem a deleção do 22q quando comparado ao grupo controle. O gene BTC foi diferentemente expresso entre meningiomas com e sem deleção do 22q. Os microRNAs miR-1e miR-133b foram hipoexpressos em meningiomas com deleção do 22q e em mengiomas sem deleção do 22q.Introduction: Among the primary tumors of the Nervous System, the meningioma is the most frequently diagnosed type, accounting for 35.5% of cases, considering all age groups. The genesis of meningiomas is a complex process that involves accumulation of genetic alterations, the most important event being the deletion in the long arm of chromosome 22. Understanding the initiation and growth of meningiomas at the molecular level can help developing new targets for therapy and, in this context, has been highlighted in the last decade the study of microRNAs (miRNAs). MiRNAs are a class of small non-coding RNAs which regulates gene expression and plays a crucial role in the development of many types of cancer. The recognition of their role in the pathophysiology of brain tumors has been coming into prominence. The aim of this study is to understand the involvement of chromosome 22q deletion in the expression profile of genes and miRNAs in meningiomas grade I and, with that, allow for a better understanding of its nature which may propose potential targets for new modalities of molecular therapy in the future. Patients and methods: In a previous study of our group, a global analysis by microarray methodology of genes and microRNAs was performed. Firstly, for group determination, a FISH technique analysis was done to identify which samples had the deletion of chromosome 22q and which had not and, by microarray analysis, were selected microRNAs and genes for validation by real-time PCR. In our present study 15 samples in each group were used: one group of meningiomas with deletion of chromosome 22q, a second one of meningiomas without deletion on chromosome 22q and a control group with 15 samples of normal arachnoid. The genes selected were ACVR1C, CCL18, VGLL3, ASPN, OGDHL and BTC and the miRNAs were miR-1 and miR-133b. Results and Conclusions: The genes and microRNAs selected by microarray analysis and validated by real-time PCR were differently expressed between meningiomas with deletion of chromosome 22q and meningiomas without deletion of chromosome 22q. The genes ACVR1C, CCL18 and VGLL3 were downregulated in both groups of meningiomas, either with deletion of chromosome 22q and without chromosome 22q deletion. The ASPN gene was downregulated in meningiomas without deletion of 22q when compared to the control group. The OGDHL gene was upregulated in meningiomas without deletion of 22q when compared to the control group. BTC was differentially expressed between meningiomas with and without deletion of 22q. The microRNAs miR-1 and miR-133b were downregulated in meningiomas with deletion of 22q and in mengiomas without deletion of 22q.
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Lombardi, Ismael Augusto Silva [UNESP]. "Avaliação do perfil de expressão gênica em meningiomas pela técnica de Nanostring." Universidade Estadual Paulista (UNESP), 2017. http://hdl.handle.net/11449/150100.
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Introdução: meningiomas são os tumores intracranianos mais comuns, correspondendo a 36% dos casos. A Organização Mundial de Saúde (OMS) classifica estes tumores em três graus histológicos: benigno (grau I), atípico (grau II) e anaplásico ou maligno (grau III), sendo que quanto maior o grau, maior a agressividade. Apesar da maior parte das lesões serem benignas, o comprometimento de estruturas na base de crânio e do parênquima cerebral, com taxas de recidiva mais altas em tumores grau II e III, tornam desafiador o tratamento de meningiomas ainda nos dias atuais. A compreensão das alterações moleculares em meningiomas podem contribuir para a identificação de marcadores de agressividade e possíveis novos alvos terapêuticos. A técnica Nanostring é realizada através de contagem digital e atualmente considerada a técnica de larga escala mais sensível. Até o momento, não foram identificados trabalhos em meningiomas utilizando Nanostring. Objetivo: avaliar o perfil de expressão gênica e suas principais vias de meningiomas através da técnica de Nanostring. Pacientes e métodos: foram avaliadas as expressões de aproximadamente 800 genes, através do Kit PanCancer Nanostring, em 17 meningiomas (6 benignos, 6 atípicos e 5 malignos) e 6 aracnóides controle. Os resultados obtidos foram analisados através de ferramentas de bioinformática (R Statistics, Cytoscape e bases de dados online DAVID e COSMIC). Os resultados obtidos foram tabulados em forma de heatmaps e analisados através de plataformas de base de dados online para identificação de vias e redes entre os diferentes graus tumorais Resultados e discussão: os meningiomas benignos e atípicos mostraram similaridade entre seus perfis de expressão e vias significativas, sugerindo que os tumores grau II podem se originar da transformação de tumores benignos. A via de ciclo celular tem componentes hiperregulados nos três graus de tumores, em número maior nas lesões grau II e III. Reguladores desta via elevados, como TP53 e BAX, podem contribuir para balancear seus efeitos mitogênicos, principalmente nos tumores benignos e atípicos. Conclusão: meningiomas benignos e atípicos apresentam similaridades em seus perfis de expressão e vias significativas e sugerindo que lesões grau II podem decorrer da transformação de tumores benignos. A via ciclo celular pode estar associada à agressividade em meningiomas, sendo maior o número de seus componentes hiperexpressos conforme maior o grau histológico dos tumores. Estudos futuros com maior número de tumores são necessários para comprovar os achados deste estudo.
Introduction: Meningiomas are the most common intracranial tumors and corresponding to 36% of all cases. The World Health Organization (WHO) classifies these tumors into three histological grades: benign (grade I), atypical (grade II) and anaplastic or malignant (grade III), and the higher the degree, the greater the aggressiveness. Although most lesions are benign, compromised structures at the skull base and cerebral parenchyma, with higher relapse rates in grade II and III tumors, make the treatment of meningiomas challenging, even in these days. The understanding of the molecular alterations in meningiomas can contribute to the identification of aggressive markers and possible new therapeutic targets. The Nanostring technique is performed through digital counting and is currently considered the most sensitive large-scale technique. To date, no work on meningiomas has been identified using Nanostring. Objetive: to evaluate the gene expression profile and its main pathways in meningiomas by Nanostring technique. Patients and methods: Approximately 800 genes were evaluated by the PanCancer Nanostring Kit in 17 meningiomas (6 benign, 6 atypical and 5 malignant) and 6 control arachnoids. The results were analyzed through bioinformatics tools (R Statistics, Cytoscape and DAVID and COSMIC online databases). The results were tabulated in heatmaps and analyzed through online database platforms for identification of pathways and networks between different tumor degrees. Results and discussion: benign and atypical meningiomas showed similarity between their expression profiles and significant pathways, suggesting that grade II tumors can originate from the transformation of benign tumors. The cell cycle pathway has components that are hyperregulated in the three tumor grades, which are higher in grade II and III lesions. Regulators of this elevated pathway, such as TP53 and BAX, may contribute to balance their mitogenic effects, especially in benign and atypical tumors. Conclusion: benign and atypical meningiomas present similarities in their expression profiles and significant pathways and suggesting that grade II lesions may result from the transformation of benign tumors. The cell cycle pathway may be associated with aggression in meningiomas, with a higher number of hyperexpressed components as the histological grade of the tumors increases. Further studies with a greater number of tumors are needed to confirm the findings of this study.
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Lombardi, Ismael Augusto Silva. "Avaliação do perfil de expressão gênica em meningiomas pela técnica de Nanostring." Botucatu, 2017. http://hdl.handle.net/11449/150100.
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Orientador: Marco Antonio ZaniniResumo: Introdução: meningiomas são os tumores intracranianos mais comuns, correspondendo a 36% dos casos. A Organização Mundial de Saúde (OMS) classifica estes tumores em três graus histológicos: benigno (grau I), atípico (grau II) e anaplásico ou maligno (grau III), sendo que quanto maior o grau, maior a agressividade. Apesar da maior parte das lesões serem benignas, o comprometimento de estruturas na base de crânio e do parênquima cerebral, com taxas de recidiva mais altas em tumores grau II e III, tornam desafiador o tratamento de meningiomas ainda nos dias atuais. A compreensão das alterações moleculares em meningiomas podem contribuir para a identificação de marcadores de agressividade e possíveis novos alvos terapêuticos. A técnica Nanostring é realizada através de contagem digital e atualmente considerada a técnica de larga escala mais sensível. Até o momento, não foram identificados trabalhos em meningiomas utilizando Nanostring. Objetivo: avaliar o perfil de expressão gênica e suas principais vias de meningiomas através da técnica de Nanostring. Pacientes e métodos: foram avaliadas as expressões de aproximadamente 800 genes, através do Kit PanCancer Nanostring, em 17 meningiomas (6 benignos, 6 atípicos e 5 malignos) e 6 aracnóides controle. Os resultados obtidos foram analisados através de ferramentas de bioinformática (R Statistics, Cytoscape e bases de dados online DAVID e COSMIC). Os resultados obtidos foram tabulados em forma de heatmaps e analisados através de plataf... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: Introduction: Meningiomas are the most common intracranial tumors and corresponding to 36% of all cases. The World Health Organization (WHO) classifies these tumors into three histological grades: benign (grade I), atypical (grade II) and anaplastic or malignant (grade III), and the higher the degree, the greater the aggressiveness. Although most lesions are benign, compromised structures at the skull base and cerebral parenchyma, with higher relapse rates in grade II and III tumors, make the treatment of meningiomas challenging, even in these days. The understanding of the molecular alterations in meningiomas can contribute to the identification of aggressive markers and possible new therapeutic targets. The Nanostring technique is performed through digital counting and is currently considered the most sensitive large-scale technique. To date, no work on meningiomas has been identified using Nanostring. Objetive: to evaluate the gene expression profile and its main pathways in meningiomas by Nanostring technique. Patients and methods: Approximately 800 genes were evaluated by the PanCancer Nanostring Kit in 17 meningiomas (6 benign, 6 atypical and 5 malignant) and 6 control arachnoids. The results were analyzed through bioinformatics tools (R Statistics, Cytoscape and DAVID and COSMIC online databases). The results were tabulated in heatmaps and analyzed through online database platforms for identification of pathways and networks between different tumor degrees. Results an... (Complete abstract click electronic access below)
Doutor
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Paiva, Neto Manoel Antonio de [UNIFESP]. "Comparação entre as vias supraorbitaria e endonasal transesfenoidal estendida para o tratamento de meningiomas da região tubérculo selar." Universidade Federal de São Paulo (UNIFESP), 2009. http://repositorio.unifesp.br/handle/11600/9218.
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Publico-108c.pdf: 149157 bytes, checksum: a1e7b8125374a3aacc36ff80e1c8226d (MD5)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Objetivo: Comparar duas vias de abordagem cirúrgicas utilizadas no tratamento de meningiomas da região do tubérculo selar. As vantagens relativas, desvantagens e critérios de seleção para tratamento destes tumores foram avaliados. Métodos: Trinta e um pacientes portadores de meningiomas da região do tubérculo selar submetidos a 33 procedimentos (craniotomia supraorbitária superciliar e/ou endonasal transesfenoidal estendida) foram avaliados retrospectivamente através de análise de prontuários, imagens e vídeos cirúrgicos. Resultados: Dos 31 pacientes, 12 foram submetidos exclusivamente à abordagem endonasal transesfenoidal estendida, 17 a craniotomia supraorbitária superciliar e dois a ambas as vias; seis já haviam sido submetidos a cirurgia anterior. Meningiomas abordados pela via supraorbitária foram maiores em relação a via endonasal 34±9 mm versus 25±8 mm, respectivamente (p=0,005). Endoscopia foi utilizada em 85,7 por cento dos acessos endonasais e em 21 por cento dos acessos supraorbitários, (p
CAPES: 0308-07-2
TEDE
BV UNIFESP: Teses e dissertações
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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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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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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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Hilbig, Arlete. "Estudo imuno-histoquímico de receptores hormonais em meningeomas." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 1996. http://hdl.handle.net/10183/115310.
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Os autores realizaram uma avaliação de 246 casos de meningeomas diagnosticados no Departamento de Patologia da Fundação Faculdade Federal de Ciências Médicas de Porto Alegre durante 25 anos (março de 1968 a março de 1993). Esses tumores foram classificados como típico, atípico, anaplásico e papilar segundo critérios previamente definidos. Desses casos foram separados, aleatoriamente, 116 tumores (60 típicos, 46 atípicos, 9 anaplásicos e 1 papilar) e realizada técnica imuno-histoquímica para receptores de estrógeno e progesterona com o objetivo de determinar se existe diferença entre tumores típicos e não típicos em relação aos receptores hormonais. Entre os critérios utilizados para definição de tumores não típicos, a invasão do SNC predominou com 62,3% dos casos. Áreas de necrose estiveram presentes em 45,9% dos meningeomas, 36% apresentaram aumento do número de mitoses, 39,3% foram hipercelular e 32,8% mostraram anaplasia citológica. Os meningeomas foram típicos em 75,22% dos casos, atípicos em 19,1%, anaplásicos em 4,47% e papilar em 1,21%. A localização supratentorial foi mais freqüente em ambos os grupos (típicos e não típicos) e houve predomínio pelo sexo feminino. A faixa etária mais acometida foi entre 51 e 60 anos. Houve recidiva em 3,78% dos meningeomas típicos, em 42,55% dos atípicos, 45,45% dos anaplásicos e não houve recidiva nos 3 casos de tumores com características papilares. A técnica imuno-histoquímica para receptores de estrógeno foi negativa em todos os meningeomas estudados. Os receptores de progesterona foram detectados, pela imuno-histoquímica, em 58,33% dos meningeomas típicos e em 48,21% dos tumores não típicos. Essa diferença não foi estatisticamente significativa. Entretanto, considerando individualmente os critérios utilizados para seleção dos não típicos, os tumores que apresentaram, de forma concomitante, invasão do SNC e aumento da taxa mitótica ou necrose, bem como a soma das três característica, foram predominantemente negativos para receptor de progesterona (p=0,038; p=0,001 e p=0,044 respectivamente). Os autores concluem que os critérios utilizados para definição de típicos e não típicos foram adequados para predizer maior chance de recidiva tumoral; que os receptores de estrógeno não estão presentes em meningeomas; que receptores de progesterona estão presentes na maioria dos meningeomas estudados; que a presença de receptor de progesterona isoladamente não é suficiente para predizer maior malignidade tumoral; e que nos tumores que apresentam invasão do SNC associado a áreas de necrose e/ou aumento da taxa mitótica, predominaram os negativos para receptor de progesterona, fazendo crer que esse grupo deve apresentar resposta pobre a uma possível manipulação hormonal.The authors assessed 246 cases of meningiomas, diagnosed in the Pathology Department of Fundação Faculdade Federal de Ciências Médicas de Porto Alegre during 25 years (from March 1968 to March 1993). Those tumors were classífied as typical, atypical, anaplastic, and papillary, according to previously defined criteria. From this cases, 116 tumours (60 typical, 46 atypical, 9 anaplastic and 1 papillary) were randomiy selected, being used an immunohistochemical technique for estrogen and progesterone receptors, attempting to determine if there is any difference between typical and non-typical tumours, in relation to hormone receptors. Among the criteria used to define non-typical tumours, brain invasion was predominant in 62,3%. There were areas of necrosis in 45,9% of meningiomas, 36% displayed increased mitotic activity, 39,3% were hypercellular, and 32,8% cytological anaplasia. Meningiomas were typical in 75,22%, atypical in 19,1%, anaplastic in 4,47%, and papillary in 1,21% of the cases. Supratentorial location was more frequent in both groups (typical and nontypical), and female gender predominated. The most afflicted age group was between 51 and 60 years of age. There was recurrence in 3,78% of typical. 42,55% of atypical. 45,45% of anaplastic, and there was no recurrence in those tumours with papillary fegtures. The immunohistochemical technique to estrogen receptors was negative in ali meningiomas studied. Progesterone receptors were detected by immunohistochemstry in 58,33% of typical, and in "48,21% of non-typicai meningiomas. This difference was not statisticaliy significant. However, individually considering the criteria used for selection of non-typical tumours, those that concurrently displayed brain invasion and increased mitotic activity or necrosis, as well as the summation of those three features, were predominantiy negative for progesterone receptors (respectively p=0,038; p=0,001; and p=0,044). The authors conclusion was that the criteria used to define typical and nontypical were adequate to predict a higher chance of tumour recurrence, that estrogen receptor were not present in meningiomas; that progesterone receptors in isolation is not enough to predict a higher tumoral malignancy; and in tumours that showed brain invasion. associated to necrosis and/or increased mitotic activity, there was a predominance of negatives to progesterone receptors, infering this group should display a poor response to a possible hormonal manipulation.
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Goncalves, Nicholas. "Transorbital Endoscopic Surgery for Sphenoid Wing Meningioma: Long-term Outcomes & Surgical Technique." Master's thesis, Faculty of Health Sciences, 2020. http://hdl.handle.net/11427/32268.
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Sphenoid wing meningiomas are benign tumors that result in proptosis, visual impairment and pain. Traditional open surgical approaches are associated with significant morbidity. Transorbital endoscopic surgery has been developed as a minimally invasive approach to gain access to these tumors and address the main presenting symptoms. The aim of the study was to assess long term vision and proptosis outcomes in patients undergoing a transorbital endoscopic resection of sphenoid wing meningioma using a combined endonasal, precaruncular and extended superior eyelid approach and to describe the surgical approach. Materials & Methods A retrospective chart review was conducted in 21 patients with lateral sphenoid wing meningioma at Groote Schuur Hospital & Cape Town Mediclinic from 2015–2019. All patients had undergone a transorbital endoscopic subtotal resection (Simpson grade II – IV) by the same surgical team. Vision was assessed using a Snellen chart and proptosis measured in mm using a Hertel exophthalmometer by an ophthalmologist. Measurements were taken at 6 weeks, 6 months and at 1 year postoperatively and compared to pre-operative values. Patients were categorized according to the WHO classification of vision into group A (blind), group B (low vision) & group C (normal vision) according to their pre-operative visual acuity. Nonparametric statistical tests employing the Wilcoxon Signed-Ranks Test were used for analysis. Statistical significance was determined by a confidence interval of 0.95, p = < 0.05 for both visual acuity (converted to LogMar) and proptosis in mm. Results A total of 21 patient charts were reviewed. The mean age of presentation was 48.8 years (range 34-79 years), and the majority of patients were female (20/21 = 95%). The most common presenting complaints were loss of vision (100%), proptosis (95%) and headache (76%). Preoperative visual results were as follows: 10 (48%) in group A (blind), 4 (19%) in group B (low vision) and 7 (33%) in group C (normal vision). In group A, 6 (60%) remained unchanged, 2 (20%) deteriorated & 1 (10%) improved. In group B, 3 (75%) improved, and 1 (25%) remained stable. In group C, 5 (71%) improved and 2 (29%) remained stable. Vision in groups B & C showed no deterioration. Patients in group A showed no benefit from optic nerve decompression. Vision in groups B & C showed a statistically significant improvement at 6 weeks [95% CI] (p = 0.021). This trend extended to long term follow up at 6 months [95% CI] (p= 0.021) and 1 year [95% CI] (p = 0.0054) postoperatively. Proptosis initially decreased, proving statistical significance at 6 weeks [95% CI] (p = 0.0054) postoperatively. The decrease at 6 months (p = 0.08) was not statistically significant and trended towards an increase in proptosis by 1 year (p = 0.78) postoperatively. The mean hospital stay was 2.7 days (range 2 – 4 days). The majority of tumors were histologically classified as WHO grade I. Conclusion Endoscopic medial optic canal decompression prior to transorbital multiportal surgery for sphenoid wing meningioma stabilizes or improves visual acuity for at least 1 year. Lateral orbitotomy via a superior eyelid approach and subtotal tumor resection initially decreases proptosis, but in the long term, returns to its preoperative state by 1 year if the main tumor component is not addressed. The earlier that medial optic nerve decompression is performed and the better the preoperative visual acuity, the greater the likelihood of favorable long-term visual outcomes.
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King, Jamie N. "Phase I Clinical Trial of Recombinant Oncolytic Newcastle Disease Virus for Intracranial Meningioma." Thesis, Virginia Tech, 2017. http://hdl.handle.net/10919/86617.
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Meningioma is one of the most commonly diagnosed intracranial tumors in dogs and humans. Treatment failures resulting in local recurrence and death remain common in tumors of high grade, prompting a need for additional therapeutic options that are both effective and affordable.
Genetic modification of the LaSota strain of Newcastle Disease Virus (rLAS) has allowed the virus' fusion protein cleavage site to be replaced with that belonging to urokinase plasminogen activator (rLAS-uPA). This site is cleavable exclusively by the uPA receptor (uPAR), which is overexpressed in canine meningioma. The rLAS-uPA represents a targeted therapy that has the potential to be efficacious against meningioma when administered systemically.
A Phase I clinical trial was designed to evaluate the safety and preliminary efficacy of rLAS-uPA administered to dogs with presumptive intracranial meningioma. The primary endpoint was to define the safety of rLAS-uPA, as determined by serial clinical and laboratory assessments during and after viral administration, using standard toxicity metrics defined by the Veterinary Cooperative Oncology Group (VCOG). Secondary end-points included anti-tumor activity quantified by magnetic resonance imaging (MRI) assessment of tumor size, and characterization of immune responses to the rLAS-uPA.
Four dogs completed the trial without significant toxicity. No objective tumor responses were noted on MRI from any dog. All dogs produced antiviral antibodies and increased circulating cytokines during the course of treatment. No virus was recovered from plasma, urine, or cerebrospinal fluid. These results indicate that further investigation into the rLAS-uPA dose intensity and interval are required to further develop this therapy.Master of Science
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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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Violin, Kalan Bastos. "Neoplasias intracranianas em cães: avaliação imuno-histoquímica de marcadores de proliferação celular e expressão de p53." Universidade de São Paulo, 2009. http://www.teses.usp.br/teses/disponiveis/10/10133/tde-01042011-093303/.
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O estudo das alterações neoplásicas do sistema nervoso (SN) de cães apresenta enorme desafio devido suas particularidades, entre as espécies de animais domésticos o cão Canis familiares é o que apresenta a maior ocorrência destes neoplasmas. O desenvolvimento deste trabalho visa estabelecer o estudo anátomopatológico, molecular e epidemiológico em neurooncologia veterinária, avaliando pela técnica de imuno-histoquímica marcadores da proliferação celular PCNA e Ki-67, expressão da proteína p53 e marcadores de diferenciação celular. Foram utilizados neste estudo 18 animais, da espécie canina, que deram entrada ao Serviço de Patologia vinculado ao Hospital veterinário (HOVET) e ao Departamento de Patologia da Faculdade de Medicina Veterinária e Zootecnia da Universidade de São Paulo, e que tiveram diagnóstico de neoplasia intracraniana primária confirmado, entre eles (8) meningiomas e (3) astrocitomas. Não houve predileção sexual e a idade média do aparecimento tumoral foi de 9 anos. O valor médio do índice proliferativo (IP) de meningiomas benignos para PCNA é 4,8% e Ki-67 é 2,8%, no astrocitoma fibrilar o valor do IP é para PCNA 1% e Ki-67 1%, no astrocitoma anaplásico o valor do IP é para PCNA 10% e Ki-67 5% e no xantoastrocitoma pleomórfico o valor do IP é para PCNA 20% e Ki-67 4%.Não foi detectada alterações em p53 e o IP foi útil para definir o comportamento tumoral benigno ou maligno e dois tipos tumorais que não haviam sido descritos em cães: xantoastrocitoma pleomórfico e tumor de parênquima pineal de diferenciação intermediária puderam ser diagnosticados graças ao conjunto de informações coletadas, morfologia celular, marcadores de diferenciação celular e índice proliferativo.The study of neoplastic alterations of dogs nervous system (NS) presents huge challenges due their particularities, between domestic animals species the dog Canis familiars presents the highest of these neoplasms. The development of this research aims to establish the anatomical-pathological, molecular and epidemiology study in veterinary neuro-oncology, evaluating by Immunohistochemistry technique markers of cell proliferation PCNA and Ki-67, expression of p53 protein and markers of cell differentiation. In this study were used 18 animals, dogs, which had entry at the Pathology Service of the Veterinary Hospital (HOVET) and at the Department of pathology from Faculdade de Medicina Veterinária e Zootecnia of University of São Paulo, which had confirmed diagnose of primary intracranial neoplasia, among them (8) meningiomas and (3) astrocytomas. There wasn\'t sexual preference and the mean age of tumor manifestation was 9 years old. The mean value of labelling index (LI) of benign meningiomas for PCNA is 4,8% and Ki-67 is 2,8%, in fibrillary astrocytoma the mean value of LI is 1% for PCNA and 1% for Ki-67, in anaplastic astrocytoma the mean value of LI is 10% for PCNA and 5% for Ki-67 and in pleomorphic xanthoastrocytoma the mean value of LI is 20% for PCNA and 4% for Ki-67. The p53 alterations wasn\'t detected and the LI was useful to set the benign or malign tumor behavior and two tumor types which had not been described in dogs: pleomorphic xanthoastrocytoma and pineal parenchymal tumour of intermediate differentiation could be diagnosed through the set of information collected, cell morphology, markers of cell differentiation and labelling index.
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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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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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Boyle-Walsh, Elizabeth Ann. "Investigations into the roles of female hormones and cytokines on meningioma cell proliferation in vitro." Thesis, University of Liverpool, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.284221.
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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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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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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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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.
Full textAbstract:
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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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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Peyrard, Myriam. "From a candidate region to gene characterization : analysis of three new genes with respect to meningioma tumorigenesis /." Stockholm, 1998. http://diss.kib.ki.se/search/diss.se.cfm?19980617peyr.
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Hatchell, Hayley. "The relationship between docohexanoic acid (DHA) and L-serine, providing an insight into the biochemistry of meningioma." Thesis, University of Central Lancashire, 2017. http://clok.uclan.ac.uk/23985/.
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As far back as the 1920s, Otto Warburg observed that cancerous cells display an altered state of metabolism surrounding lipid biosynthesis. However, only until recently has metabolic reprogramming been a recognised hallmark of the disease. The number of cancer cases diagnosed is set to triple by 2030, demonstrating the need for disease prevention, improved diagnostic testing and personalised treatment therapies. However, with some cancers occurring in the brain and spinal cord, the type of treatment available can become challenging due to their locality. Such cancer types include meningioma and glioma which are the most common brain tumours diagnosed. An initial study involving human meningioma tissue revealed unusually high levels of the phosphatidylserine enriched with docosahexaenoic acid (DHA). In this study, the metabolism surrounding lipid biosynthesis was examined to establish if such alterations in lipid profiles were related to an altered state of metabolism. From the results gained, it can be suggested that meningioma does have an altered state of metabolism, evolving around serine as opposed to DHA. From the grade I and grade II meningioma tissues immunochemically examined, positive expressions of pyruvate kinase isoform 2 (PKM2) and phosphoglycerate dehydrogenase (PHGDH) were shown. Therefore, the results demonstrated that within meningioma tissues, serine can allosterically regulate the flux through glycolysis. The association that serine presence alone can alter the metabolic flux was demonstrated in the model organism, Lipomyces starkeyi. Those L. starkeyi cells supplemented with serine, displayed a 50% reduction in the amount of radiolabelled acetate taken up during exponential and stationary growth phases. The radiolabelled study also highlighted that with serine presence, de novo lipid biosynthesis was altered. Once synthesised, these neutral lipids go on to be 4 stored in membrane bound organelles. Within the phenotype of cancerous cells, such storage of neutral lipids into lipid droplets prevent lipotoxicity. The light microscopy study of L. starkeyi cells supplemented with serine demonstrated that the formation of such lipid droplets was enhanced during lipid accumulation. These findings suggest that the production, storage and mobilisation of lipids within serine supplemented cells are adapted to cellular requirements, promoting a cancerous phenotype. In order to gain an insight into the potential impact that an altered metabolic state may give to meningioma, a liposomal study was developed. Supplementation of both phosphatidylserine-consisting liposomes, as well as tumour-derived liposomes, enhanced the cellular viability of the non-cancerous cell line, SVG, during exponential phase. The supplementation of meningioma-derived liposomes also increased the viability of the non-cancerous human fetal glial SVG cell line, similar to that observed with phosphatidylserine containing liposomal preparations. Therefore, the data suggest that in fact, the phospholipid (phosphatidylserine), rather than the fatty acid (DHA) plays a role in cellular viability. It is concluded that the results gained from this study can be used clinically in the diagnosis and management of meningioma as well as other diseased cells displaying ectopic lipid accumulation. The observation that meningioma has an altered biochemistry may provide guidance when histologically grading meningioma tumours. For those tumours expressing the enzymes involved in serine biosynthesis, such as PKM2 and PHGDH, a targeted treatment therapy surrounding enzyme inhibitors can be examined. By targeting serine biosynthesis, the resources needed to enable a cancerous phenotype are depleted. Future research can examine such targeted therapies utilizing either the developed model organism, L. starkeyi or the conventional SVG and U87 cell lines.
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Zhang, Xiaoxue. "1,25-Dihydroxyvitamin D3-Induced Genes in Osteoblasts: Uncovering New Functions for Meningioma 1 and Semaphorin 3B in Skeletal Physiology." Case Western Reserve University School of Graduate Studies / OhioLINK, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=case1236358419.
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BASTOS, Carlos Eduardo Matos Carvalho. "Alterações genéticas e epigenéticas em meningiomas na população paraense." Universidade Federal do Pará, 2013. http://repositorio.ufpa.br/jspui/handle/2011/4511.
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CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico
CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
FAPESPA - Fundação Amazônia de Amparo a Estudos e Pesquisas
Os meningiomas são os tumores intracranianos mais frequentes, originando-se das meninges que revestem o cérebro e cordão espinhal. Apesar de terem sido um dos primeiros neoplasmas sólidos estudados citogeneticamente, ainda são escassos os estudos genéticos e epigenéticos nesses tumores. O presente trabalho teve como objetivo investigar alterações genéticas e epigenéticas que pudessem contribuir na iniciação e progressão tumoral em meningiomas na população paraense. Essa tese está subdivida em três capítulos. No Capítulo I foi investigada a associação entre o polimorfismo MTHFR C677T e meningioma em 23 pacientes da população paraense, utilizando 96 indivíduos sem histórico de lesões pré-neoplásicas como grupo controle. Essa associação não foi encontrada, apesar de sugerir um aumento não estatisticamente significante no risco de desenvolver meningioma em portadores do genótipo TT quando comparados ao genótipo CC. No Capítulo II foi avaliado o padrão de metilação em duas famílias do microRNA124 em meningiomas na população paraense. Hipermetilação na região promotora de miRN124a2 e miRNA124a3 parece ser um evento frequente, uma vez que foi encontrada em 73,9% e 69,56% das amostras analisadas, respectivamente. No Capítulo III, foi analisado o padrão de metilação dos genes APC, BRCA1, CDH1, CDH13, CDKN2A, DAPK1, ESR1, FHIT, GSTP1, MGMT, MLH1, NEUROG1, PDLIM4, PTEN, RARB, RASSF1, RUNX3, SOCS1, TIMP3, TP73, VHL e WIF1 em um meningioma de grau I e um de grau II através de uma placa comercial desenvolvida através da tecnologia MethylScreen. O padrão de metilação do gene CDKN2B também foi analisado na amostra coletada em 25 pacientes com meningioma através da conversão por bissulfito, PCR e sequenciamento direto. O gene RASSF1A apresentou-se metilado em 16,73% e 63,66% dos sítios CpGs analisados na amostra de meningioma de grau I e grau II, respectivamente. O gene RUNX3 se apresentou metilado apenas na amostra de grau II em 52,88% dos sítios CpG analisados. Nossos resultados apontam a importância das alterações epigenéticas na tumorigênese e progressão tumoral em meningiomas.
Meningiomas are the most common intracranial tumors that originate from the meninges surrounding the brain and spinal cord. Despite meningiomas were among the first solid neoplasms to be studied cytogenetically, little is known about their genetic and epigenetic profile. This study aimed to investigate genetic and epigenetic alterations that could contribute to tumor initiation and progression in meningiomas in the population of Pará, Brazil. This thesis is subdivided into three chapters. In Chapter I we investigated the association between the MTHFR C677T and meningioma in 23 patients in the population of Pará. A total of 96 healthy individuals with no previous pre-neoplastic lesions were selected for the control group. This association was not found. Although not statistically significant, our observation suggests that the TT genotype increases the risk of developing meningioma when compared to CC genotype. In Chapter II we evaluated the methylation pattern in two members of microRNA124 family in meningiomas in the population of Pará. Hypermethylation of the promoter region of miRN124a2 and miRNA124a3 appears to be a frequent event, as was found in 73.9% and 69.56% of the samples, respectively. In Chapter III, we analyzed the methylation pattern of the APC, BRCA1, CDH1, CDH13, CDKN2A, DAPK1, ESR1, FHIT, GSTP1, MGMT, MLH1, NEUROG1, PDLIM4, PTEN, Rb, RASSF1, RUNX3, SOCS1, TIMP3, TP73, VHL and WIF1 genes in a grade I and in a grade II meningiomas through an assay developed by MethylScreen. Pattern of methylation of CDKN2B was also analyzed in 25 patients with meningioma through bisulfite conversion, PCR and direct sequencing. RASSF1A was methylated in 16.73% and 63.66% of the CpG sites analyzed in the grade I and grade II meningioma, respectively. RUNX3 is methylated only in grade II meningioma in 52.88% of the CpG sites analyzed. Our results point to the importance of epigenetic changes in tumorigenesis and tumor progression in meningiomas.
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Mocker, Kristin. "Zytogenetische und molekularbiologische Untersuchungen an intrakraniellen Meningeomen unter Anwendung der GTG-Bänderung, SKY-Technik, FISH-Analyse und genomweiter SNP-A Karyotypisierung." Doctoral thesis, Universitätsbibliothek Leipzig, 2013. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-118823.
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Meningeome sind Tumore der Hirnhäute und stellen zirka 24-30% aller intrakraniellen Tumore dar. Obwohl sie in den meisten Fällen als solitär, langsam wachsend und benigne (WHO Grad 1) beschrieben werden, ist ihr ausgeprägtes Rezidivverhalten die größte Herausforderung in der Therapie. Bisherige Arbeiten verwendeten zur genetischen Analyse von Meningeomen meist Untersuchungstechniken mit eingeschränkter (molekular-)zytogenetischer Aussagekraft. Mit der Kombination der Methoden Giemsa-Bandendarstellung (GTG-Bänderung), Spektrale Karyotypisierung (SKY-Technik), Fluoreszenz in situ Hybridisierungstechniken (FISH-Analyse) und molekulare Karyotypisierung unter Verwendung von 100K beziehungsweise 6.0 SNP-Arrays (SNP-A Karyotypisierung) sollte es möglich sein, in effizienterer Form bislang unentdeckte chromosomale Aberrationen zu identifizieren und weiterführende tumormechanistische Hinweise zu erhalten. In der vorliegenden Arbeit wurde zunächst ein multipel aufgetretenes Meningeom mit zwei Tumoren unterschiedlicher Malignität (1 WHO Grad 1; 1 WHO Grad 2) analysiert, anschließend erfolgte die Untersuchung einer Gruppe von 10 Meningeomen (5 WHO Grad 1; 5 WHO Grad 2). Bisher nicht beschriebene Aberrationen wie ein dizentrisches Chromosomen 4, die parazentrische Inversion im chromosomalen Bereich 1p36 und die balancierte reziproke Translokation t(4;10)(q12;q26) wurden detektiert. Die genomweite SNP-A Karyotypisierung ermöglichte neben der genaueren Betrachtung der zytogenetischen Ergebnisse die simultane Analyse von Blut und Tumor-DNA der Patienten und lieferte Hinweise auf konstitutionelle Aberrationen. Es zeigte sich eine signifikante Anreicherung von rekurrenten Regionen kopienneutraler Verluste der Heterozygotie als Hinweis auf das Vorliegen potenzieller segmentaler Uniparentaler Disomie (UPD) jeweils in Blut und Tumor der Patienten. Außerdem wurden nur im Tumor befindliche potentielle rekurrente segmentale UPD Regionen detektiert. Die weitere Analyse der konstitutionellen sowie somatischen segmentalen UPD hinsichtlich ihrer Rolle im Rahmen der Tumorgenese ist eine wichtige Aufgabe für die Zukunft.
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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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Baia, Gilson Soares [UNIFESP]. "Meningiomas: caracterização da indução da via de sinalização de Notch e desenvolvimento de modelo ortotópico animal." Universidade Federal de São Paulo (UNIFESP), 2008. http://repositorio.unifesp.br/handle/11600/9814.
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Publico-10890d.pdf: 1518283 bytes, checksum: 5bd6b7757a463a7b6c64cd275e3e0014 (MD5)É observado que a cascata de sinalização de Notch tem ativação desregulada em diversos tipos de cânceres. Em câncer, é descrito que a função específica da via de sinalização de Notch e dependente do contexto celular, dos tipos específicos expressos de receptores homólogos e do cruzamento de informação (crosstalk) entre as diferentes vias de sinalização. Nosso laboratório descreveu previamente, que a via de sinalização de Notch apresenta-se desregulada em meningiomas de todos os graus. Entretanto, a conseqüência funcional desta sinalização anormal de Notch e desconhecida. Neste trabalho, descrevemos que, em linhagens celulares de meningiomas, a expressão exógena do gene Hes-1, o componente efetor da via de Notch, esta associada à formação de células tetraplóides. De forma similar, a expressão exógena das formas ativas dos receptores Notch 1 e Notch2, induz ao aumento da expressão de Hes-l, que contribui para a formação de células tetraplóides. Células tetraplóides de meningioma exibem indícios de instabilidade genética, caracterizados pelo aumento da freqüência de figuras atípicas nucleares, como a presença de mitoses com fusos multipolares e de células com núcleos de tamanho aumentado. As células tetraplóides isoladas por citometria de fluxo demonstram ser viáveis em cultura, embora apresentem uma maior taxa de apoptose espontânea, quando comparadas as células diplóides. A técnica de cariotipagem espectral foi usada para demonstrar que, em comparação as células diplóides, as células tetraplóides desenvolvem uma taxa mais elevada de aberrações cromossômicas estruturais e numéricas. Nossos resultados identificam uma nova função para a via de sinalização de Notch na geração tetraplóidia e conseqüentemente de instabilidade cromossômica. Portanto, a via desregulada da sinalização de Notch pode ser um mecanismo genético inicial em meningiomas, contribuindo potencialmente para a tumorigênese..
TEDE
BV UNIFESP: Teses e dissertações
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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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Fuh, Marceline Manka [Verfasser], and Hartmut [Akademischer Betreuer] Schlüter. "Investigation of extracellular vesicles from glioblastoma multiforme and meningioma patients for cancer liquid biopsy by differential quantitative proteomics / Marceline Manka Fuh ; Betreuer: Hartmut Schlüter." Hamburg : Staats- und Universitätsbibliothek Hamburg, 2019. http://d-nb.info/1197801480/34.
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Corrêa, Sebastião Francisco Miranda. "Radiocirurgia e radioterapia estereotática no tratamento de meningeomas sintomáticos do seio cavernoso." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/5/5138/tde-27082014-101734/.
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Introdução: Radiocirurgia estereotática (RCE) e radioterapia estereotática fracionada (RCEF) são inovações modernas de procedimentos radioterápicos, de alta precisão que modelam o feixe de radiação para coincidir com o contorno da lesão, por meio de um sistema de imobilização exata do paciente ao aparelho, com definição do alvo através da fusão de imagens de RM, TC, Angiografia e PET/CT; em que pelas coordenadas de referência estereotática, determina-se que a dose de radiação de alta energia prescrita pelo médico seja depositada somente no volume-alvo, com preservação dos tecidos sadios, órgãos ou estruturas localizadas em suas adjacências. Meningeomas do seio cavernoso (MSCs) representam um problema especial porque podem evoluir comprimindo ou infiltrando estruturas neurovasculares presentes no seio cavernoso. Há evidências de que a RCE e a RCEF proporcionam controle satisfatório do crescimento dos meningeomas do seio cavernoso (MSCs) com efeitos adversos reduzidos. Objetivo: Avaliar resultados da avaliação clínica e da neuroimagem de doentes sintomáticos com MSCs tratados com RCEF ou RCE exclusivamente ou de modo adjuvante à neurocirurgia. Casuística e métodos: Estudo tipo coorte e retrospectivo sobre a avaliação de 89 doentes com MSC sintomático tratados com RCE (36%) ou RCEF (64%) entre janeiro de 1994 e março de 2009 e acompanhados até o final de 2012. Haviam sido submetidos à ressecação neurocirúrgica parcial (Simpson IV) ou à biopsia (Simpson V) previamente à radioterapia 29,2% dos doentes. A dose média de RCE foi de 14Gy, e a dose total de RCEF variou entre 50,4 e 54Gy, sendo fracionada em 1,8-2Gy/dose/dia. Resultados: O período de acompanhamento variou entre 36 e 180 meses (mediana de 73 meses). A percentagem de melhora dos sintomas neuroclínicos individuais e de melhora clínica e radiológica (p > 0,05) apresentou valores semelhantes nos doentes tratados com RCE ou RCEF, sendo respectivamente de 41,6% e 48,3%. Em 37% dos doentes, houve manutenção de, pelo menos, uma queixa neurológica apresentada antes do tratamento e, em 43,8%, a imagem do MSC manteve-se inalterada. O período livre de progressão do MSC em 5, 10 e 15 anos foi de 98,8%, 92,3% e 92,3%, respectivamente. Houve progressão da doença em quatro doentes (4,5%). A melhora dos sintomas neurológicos em doentes submetidos previamente à neurocirurgia ocorreu de maneira mais lenta em relação aos não operados, em razão de manipulação de nervos cranianos. Alguns sintomas pós-operatórios, como a ptose palpebral unilateral, persistiram permanentemente. Nenhuma complicação grave foi observada. Sete doentes apresentaram neuropatia óptica transitória durante 3 meses que melhorou com o uso de corticoides, dois neuropatia trigeminal que melhorou com uso de esteroides e um doente apresentou obstrução total da artéria carótida interna sem repercussão neurológica. Letargia e cefaléia foram os sintomas temporários imediatos mais frequentes. Conclusões: A RCEF e a RCE são métodos seguros e eficazes para tratar doentes com MSC sintomático. Proporcionam melhora ou estabilização da sintomatologia na maioria dos casos, e estabilização ou regressão do tumor demonstrado pela neuroimagem em mais de 90% deles. Ocorreu recuperação dos sintomas neurológicos preexistentes mais rapidamente em doentes não submetidos previamente à neurocirurgia. Houve recorrência do tumor em 4,5% dos doentes. Em até 15 anos de acompanhamento, não se evidenciou indução tumoral com o tratamentoIntroduction: Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRS) are modern innovations in radiotherapy procedures, precision shaping the radiation beam to match the contour of the lesion, through a system of accurate patient immobilization to the device, defining target through the fusion of MRI, CT, angiography and PET / CT, which is determined by reference to stereotactic coordinates. The radiation dose of high energy prescribed by the doctor to be delivery only in the target interest, with preservation of healthy tissues, organs or structures located in their vicinity. Cavernous sinus meningiomas (CSMs) pose a special problem because they can evolve compressing or infiltrating the neurovascular structures present of the cavernous sinus. There are evidences that SRS and FRS are efficient in the treatment of CSMs. Objectives: The evaluation of the long-term clinical results and neuroimaging findings in patients with symptomatic CSM treated with FSRT or SRS as single therapy or after a previous neurosurgical treatment. Patients and methods: Retrospective cohort study involving 89 patients with symptomatic CSMs treated with SRS (36%) or FSRS (64%) from January 1994 to March 2009, and followed until the end of 2012. Previous neurosurgical partial resection (Simpson IV) or biopsies (Simpson V) had been performed in 29.2% of the patients. The median dose of SRS was 14Gy and the total dose of FSRT ranged from 50.4 to 54Gy, fractionated in 1.8 to 2Gy/dose/day. Results: The follow-up period ranged from 36 to 180 months (median= 73months). There was improvement in the individual symptoms and in the clinical and radiological findings regardless the radiotherapeutic method in 41.6% and 48.3% of the patients treated with SRS or FSRT, respectively (p > 0,05). In 37% of the patients, at least one neurological complaint present before the treatment did not change and in 43.8% patients, the image of the tumor remained stable. The progression-free survival in 5, 10 and 15 years was 98.8%, 92.3% and 92.3%, respectively. The improvement of neurological symptoms in patients previously treated with neurosurgery was slower or did not occur as in nonpreviously operated patients. Lethargy and headache were the most frequent transient immediate post-radiotherapy symptoms. Seven patients presented transient optic neuropathy during 3 months and improved with corticosteroids, 2 presented trigeminal neuropathy that remitted rapidly with steroids, and one, had total occlusion of the internal carotid artery without neurological consequences. Conclusions: Both FSRT and SRS were equally safe and effective in the management of symptomatic CSMs. There was improvement or stabilization of the neurological symptoms in the majority ofthe patients and stabilization or regression of the neuroimaging of the lesion in more them 90% of them. The recovery of preexisting cranial neuropathies occurred faster and was more frequent in patients not previously treated with surgical procedure. There was recurrence in 4.5% of the patients. No radiation-induced tumor was observed term during the longest 15 years follow-up
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GUIAS, THIERRY. "Signes radiologiques et scintigraphiques des meningiomes parasagittaux : a propos d'un cas de meningiome parasagittal revele par une scintigraphie osseuse." Limoges, 1988. http://www.theses.fr/1988LIMO0205.
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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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CARLOTTI, VINCENTELLI NICOLE. "Meningiome insulaire." Aix-Marseille 2, 1988. http://www.theses.fr/1988AIX20314.
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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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Da, Silva Manuel. "Évaluation de la qualité de vie en relation avec la santé des patients atteints de méningiome." Thesis, Toulouse 2, 2016. http://www.theses.fr/2016TOU20124.
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L’évaluation de la qualité de vie des patients avec méningiome revêt un intérêt clinique important pour les futures modalités de prise en charge. Néanmoins les outils les plus spécifiques à disposition des praticiens et chercheurs aujourd’hui ont été élaborés à destination de patients avec des pathologies cancéreuses. Le caractère bénin des méningiomes (95% des cas) tend à influencer différemment la qualité de vie de ces patients. Afin d’évaluer la qualité de vie des patients avec méningiome, nous avons élaboré et validé un questionnaire spécifique : le M-QoL. Un groupe composé de 25 spécialistes d’horizons différents ont participé à l’élaboration du questionnaire. Ce dernier a été administré à 128 participants, dont 85 ont également rempli le questionnaire une seconde fois dans les semaines suivantes. Les résultats des M-QoL ont été comparés aux questionnaires WHOQOL-Bref de l’OMS pour 122 participants. 70 participants ont également bénéficié d’une évaluation neuropsychologique. Les analyses démontrent les qualités psychométriques du questionnaire (validité, fidélité, sensibilité) et des corrélations ont été retrouvées avec les évaluations cognitives. L’évaluation de la qualité de vie avec le M-QoL permet de mieux appréhender les difficultés rencontrées par les patients dans leur vie quotidienne. En conséquence, il est possible d’améliorer l’orientation de ces patients pour une meilleure prise en charge de leurs difficultésEvaluation of quality of life of patients with meningioma is particularly important as a clinical aspect for medical and psychological cares. Nevertheless, the most specific tools available for practitioners and researchers nowadays were implemented for cancer patients. The benign nature of meningiomas (in 95% of cases) tends to influence differently the quality of life of those patients.In order to evaluate the quality of life of meningioma patient, we’ve made and validated a specific questionnaire: the M-QoL.A group of 25 experts with different specialities participated to the development of this questionnaire. It was administrated to 128 participants, 85 of them whom completed it a second time in the following weeks. M-QoL results were compared to WHOQOL-Bref questionnaire from the WHO for 122 participants. 70 participants had benefited of a neuropsychological assessment.Analyses demonstrated psychometric qualities of the questionnaire (validity, reliability, sensitivity) and correlations were found with cognitive evaluations. Evaluation of quality of life through the M-QoL allows a better perception of the difficulties which impair the patients in everyday life.In consequences, it is possible to improve orientation of those patients for a better care of their difficulties
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Gauchotte, Guillaume. "Prolifération cellulaire et protéine HuR dans les méningiomes." Thesis, Université de Lorraine, 2014. http://www.theses.fr/2014LORR0032/document.
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Introduction et objectifs : Les méningiomes sont des tumeurs intracrâniennes pour la plupart de bas grade, dont les récidives sont cependant fréquentes. Le premier objectif de cette étude est d'évaluer la valeur pronostique de marqueurs de prolifération dans une série de 60 méningiomes. HuR (ELAV-like 1) est une protéine pro-oncogène pouvant stimuler la prolifération et la survie cellulaire. Dans la seconde partie de cette étude, nous analysons l'expression de HuR et les effets de l'inhibition de HuR sur la prolifération, l'apoptose et la résistance à l'hypoxie. Résultats : Il existe une corrélation significative entre le grade histologique et l'expression nucléaire de MCM6 (p<0,001), Ki-67 (p<0,001) et PHH3 (p<0,001), et une corrélation inverse entre ces marqueurs et la survie sans récidive (Cox ; MCM6 : p<0,001 ; Ki-67 : p=0,003 ; PHH3 : p=0,037). L'expression cytoplasmique de HuR est corrélée négativement avec la survie sans récidive (p=0,028), et positivement avec le grade (I vs II : p=0,0007), l'indice mitotique (p=0,0001), Ki-67 (p=0,0007) et MCM6 (p=0,0009). In vitro, l'inhibition de HuR (siRNA) entraîne une diminution de la croissance cellulaire (p=0,0004) et de la prolifération (Ki-67, p=0,0004), et une augmentation de l'apoptose (caspase 3 clivée, p=0,002), ces différents effets étant significativement augmentés en hypoxie. L'inhibition de HuR entraîne également une diminution de SIRT1 en normoxie (p=0,01) et en hypoxie (p=0,0006). Conclusion : MCM6 est un marqueur efficace pour identifier les méningiomes à haut risque de récidive. HuR est un marqueur de mauvais pronostic, dont l'inhibition permet de diminuer la prolifération cellulaire et d'augmenter l'apoptoseIntroduction and objectives: Meningiomas are frequent and in most of cases low grade intracranial tumors, with frequent recurrences. The first objective of this study was to evaluate the prognostic value of proliferation and cell cycle markers in a series of 60 meningiomas. HuR (ELAV-like 1) is a pro-oncogenic protein that stimulates cell proliferation and survival. In the second part of this study, the objective was to evaluate HuR expression, and the effects of HuR inhibition on proliferation, apoptosis and resistance to hypoxia. Results: We found a significant correlation between histological grade and nuclear staining for MCM6 (p<0.001), Ki-67 (p<0.001) and PHH3 (p<0.001), and an inverse correlation between these markers and reccurence free survival (Cox; MCM6: p<0.001; Ki-67: p=0.003; PHH3: p=0.037). Cytoplasm staining for HuR was significantly stronger in atypical meningiomas (grades I vs II: p=0.0007), inversely correlated with progression free survival (p=0.028), and was positively correlated with mitotic index (p=0.0001), Ki-67 (p=0.0007) and MCM6 (p=0.0009). In vitro, HuR inhibition (siRNA) led to a significant decrease of cell growth (p=0.0004) and proliferation (Ki-67, p=0.0004), and an increase of apoptosis (cleaved caspase 3, p=0.002). These effects were significantly increased under hypoxia, comparing with normoxia. When HuR was inhibited, SIRT1 was decreased, both under normoxia (p=0.01) and hypoxia (p=0.0006). Conclusion: In conclusion, MCM6 is an efficient marker to identify meningiomas with high risk of recurrence. HuR is correlated with a poor prognosis. Its inhibition allows to decrease cell proliferation and to increase apoptosis
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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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Schoultz, Eva von. "Malignant glioma : experimental studies with an estrogen-linked cytostatic." Doctoral thesis, Umeå universitet, Onkologi, 1990. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-100558.
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Malignant gliomas are the most common primary brain tumors in adults. Patients with these highly malignant tumors have an extremely poor prognosis. The situation with a highly proliferative tumor in a non-proliferating tissue should favor cytostatic treatment but so far the role of conventional chemotherapy has been adjunctive. The concentrations of three sex steroids, estradiol, progesterone and testosterone, were analyzed by radioimmunoassay after celite chromatography in brain tumor samples. Some malignant gliomas had high tissue concentrations of estradiol. Low progesterone levels may suggest steroid consumption. Estramustine (EM), a conjugate of estradiol-17ß and nornitrogen mustard had a dose-dependent antiproliferative effect on several human malignant glioma cell lines. At equimolar concentrations the inhibitory effects of the EM complex were clearly more pronounced than those of estradiol and nornitrogen mustard given alone or in combination. A specific binding protein (EMBP) is important for the cytotoxic action of EM. Using a mouse monoclonal antibody and an indirect antibodyperoxidase technique, EMBP was demonstrated in human glioma cells. Significant amounts of EMBP were also detected in human brain tumor tissue by radioimmunoassay. The mean concentrations (ng/mg protein) in 16 astrocytomas (2.6) and 7 meningiomas (5.1) were higher (p<0.001) than in 18 samples of normal brain (0.5). The presence of the specific binding protein may suggest a selective binding and effect of EM in human brain tumor tissue. Human glioma cells displayed significant uptake, retention and metabolism of estramustine phosphate (EMP). After incubation with ^H-EMP a progressive uptake of radioactivity was recorded during 24 hours. Metabolism of parent EMP into estramustine and estromustine, which is a well known part of the metabolic pathway in man, was also demonstrated. A dose- dependent increase in DNA strand breaks was recorded at EMP- concentrations ranging 10-40 yg/ml. The uptake of ®^Rb, used as a tracer for potassium to study ion transport and membrane permeability, was reduced after incubation with EMP. Scanning electron microscopy gave further evidence for membrane damage. According to flow cytometric analyses exponentially growing glioma cells were accumulated in the G2/M stage and the fraction of Gi/Gq was reduced. EM seems to attack malignant cells in a multifocal fashion on several vital functions including the microtubule, the nucleus, and the cell membrane. The intact EM complex may be important for effects related to microtubule function which add to the cytotoxic potential of its constituents. These experimental findings justify further investigations on the role of sex hormones in brain tumor growth and development and of hormone-linked cytostatics in clinical treatment.Diss. (sammanfattning) Umeå : Umeå universitet, 1990, härtill 6 uppsatser.
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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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CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico
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.