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1.
Inquiry ; 59: 469580221095824, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35549576

RESUMO

In the midst of the pandemic caused by the new coronavirus (SARS-CoV-2), researchers and governmental and non-governmental institutions are mobilizing to implement strategies to face cases of COVID-19. Aim: This study aimed to map the triage strategies for cases of COVID-19, with the purpose of identifying sources in the literature that make it possible to explore the understanding of the strategies in different contexts. A scope review was conducted with searches in the CINAHL Database, PubMed, LILACS and hand-search, considering studies carried out with users of health services and documents published by governmental and non-governmental institutions, between the years 2019 and 2020, resulting in 40 articles for full reading. To explore the key concept, thematic analysis was carried out at two levels: (1) triage strategies, (2) forms and experiences of triage. Five triage strategies were mapped: health services triage; digital triage by remote use of technologies; community triage; home visit triage and airport and port triage. The forms and experiences of mapped triages involved risk classification, diagnosis and definition of conducts or combined. The use of strategies with remote technological resources stands out, as well as the adaptation of existing scales with simple algorithms as a tendency.


Assuntos
COVID-19 , Humanos , Pandemias , SARS-CoV-2 , Triagem
2.
Rev Bras Parasitol Vet ; 30(4): e008721, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34787174

RESUMO

A serological, molecular and histopathological study was carried out in order to investigate occurrences of Toxoplasma gondii in pigs slaughtered with and without inspection service. Serum samples were collected from 60 pigs to detect anti-T. gondii antibody by indirect fluorescent antibody (IFAT). Tongue, masseter and diaphragm fragments were also collected for parasite DNA detection by means of the polymerase chain reaction (PCR) and histopathological analysis. The serological results showed that 77% (44/60) of the pigs were positive. Regarding PCR, 66.67% (40/60) were positive for T. gondii. Among the tissues evaluated, the diaphragm was the one with the highest frequency of positivity (40%; 24/60), followed by the masseter (38.33%; 23/60) and tongue (33.3%; 20/60). Histopathological changes were only observed in the diaphragm, which presented inflammatory infiltrates of lymphohistiocytic and neutrophilic types. These results not only show the potential threat of T. gondii to human health, but also demonstrate the dynamic epidemiological situation of toxoplasmosis in pigs in the city of São Luís, providing support for food security regarding pigs and for T. gondii control programs in Brazil.


Assuntos
Doenças dos Suínos , Toxoplasma , Toxoplasmose Animal , Animais , Anticorpos Antiprotozoários , Brasil/epidemiologia , Técnica Indireta de Fluorescência para Anticorpo/veterinária , Suínos , Doenças dos Suínos/diagnóstico , Doenças dos Suínos/epidemiologia , Toxoplasmose Animal/diagnóstico , Toxoplasmose Animal/epidemiologia
3.
Rev. bras. parasitol. vet ; 30(4): e008721, 2021. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1351875

RESUMO

Abstract A serological, molecular and histopathological study was carried out in order to investigate occurrences of Toxoplasma gondii in pigs slaughtered with and without inspection service. Serum samples were collected from 60 pigs to detect anti-T. gondii antibody by indirect fluorescent antibody (IFAT). Tongue, masseter and diaphragm fragments were also collected for parasite DNA detection by means of the polymerase chain reaction (PCR) and histopathological analysis. The serological results showed that 77% (44/60) of the pigs were positive. Regarding PCR, 66.67% (40/60) were positive for T. gondii. Among the tissues evaluated, the diaphragm was the one with the highest frequency of positivity (40%; 24/60), followed by the masseter (38.33%; 23/60) and tongue (33.3%; 20/60). Histopathological changes were only observed in the diaphragm, which presented inflammatory infiltrates of lymphohistiocytic and neutrophilic types. These results not only show the potential threat of T. gondii to human health, but also demonstrate the dynamic epidemiological situation of toxoplasmosis in pigs in the city of São Luís, providing support for food security regarding pigs and for T. gondii control programs in Brazil.


Resumo Realizou-se um estudo sorológico, molecular e histopatológico com o objetivo de verificar a ocorrência de Toxoplasma gondii em suínos abatidos com e sem serviço de inspeção. Foram coletados soros de 60 suínos para a pesquisa de anticorpos anti-T. gondii pela reação de imunofluorescência indireta (RIFI). Também foram coletados fragmentos de língua, masseter e diafragma para a detecção do DNA do parasito por meio da reação em cadeia da polimerase (PCR) e análise histopatológica. A análise sorológica demonstrou que 77% (44/60) dos suínos apresentaram anticorpos anti-T. gondii. Com relação ao PCR, 66,67% (40/60) foram positivos para T. gondii. Dentre os tecidos avaliados, o diafragma foi o que obteve maior frequência de positividade (40%; 24/60), seguidos de masseter (38,33%; 23/60) e língua (33,3%; 20/60). Alterações histopatológicas foram observadas apenas no diafragma, que apresentou infiltrado inflamatório do tipo linfohistiocitário e neutrofílico. Esses resultados não evidenciam apenas a ameaça potencial de T. gondii à saúde humana, mas também demonstram a dinâmica situação epidemiológica da toxoplasmose em suínos na região da cidade de São Luís, fornecendo suporte para a segurança alimentar de suínos e programas de controle de T. gondii no país.


Assuntos
Animais , Doenças dos Suínos/diagnóstico , Doenças dos Suínos/epidemiologia , Toxoplasma , Toxoplasmose Animal/diagnóstico , Toxoplasmose Animal/epidemiologia , Suínos , Brasil/epidemiologia , Anticorpos Antiprotozoários , Técnica Indireta de Fluorescência para Anticorpo/veterinária
5.
Cancers (Basel) ; 12(1)2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31963499

RESUMO

BACKGROUND: The prognostic impact of the expression profile of genes recurrently amplified in glioblastoma multiforme (GBM) remains controversial. METHODS: We investigated the RNA gene expression profile of epidermal growth factor receptor (EGFR), cyclin-dependent kinase 4 (CDK4), murine doble minute 4 (MDM4), and platelet derived growth factor receptor alpha (PDGFRA) in 83 primary GBM tumors vs. 42 normal brain tissue samples. Interphase FISH (iFISH) analysis for the four genes, together with analysis of intragenic deletions in EGFR and PDGFRA, were evaluated in parallel at the DNA level. As validation cohort, publicly available RNA gene expression data on 293 samples from 10 different GBM patient series were also studied. RESULTS: At the RNA level, CDK4 was the most frequently overexpressed gene (90%) followed by EGFR (58%) and PDGFRA (58%). Chromosome 7 copy number alterations, i.e., trisomy (49%) and polysomy (44%), showed no clear association with EGFR gene expression levels. In turn, intragenic EGFR deletions were found in 39 patients (47%), including EGFRvIII (46%) in association with EGFRvIVa (4%), EGFRvII (2%) or other EGFR deletions (3%) and PDGFRA deletion of exons 8-9 was found in only two tumors (2%). CONCLUSIONS: Overall, none of the gene expression profiles and/or intragenic EGFR deletions showed a significant impact on overall survival of GBM supporting the notion that other still unraveled features of the disease might play a more relevant prognostic role in GBM.

6.
Oncotarget ; 9(46): 28083-28102, 2018 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-29963263

RESUMO

Several classification systems have been proposed to address genomic heterogeneity of glioblastoma multiforme, but they either showed limited prognostic value and/or are difficult to implement in routine diagnostics. Here we propose a prognostic stratification model for these primary tumors based on tumor gene amplification profiles, that might be easily implemented in routine diagnostics, and potentially improve the patients management. Gene amplification profiles were prospectively evaluated in 80 primary glioblastoma multiforme tumors using single-nucleotide polymorphism arrays and the results obtained validated in publicly available data from 267/347 cases. Gene amplification was detected in 45% of patients, and chromosome 7p11.2 including the EGFR gene, was the most frequently amplified chromosomal region - either alone (18%) or in combination with amplification of DNA sequences in other chromosomal regions (10% of cases). Other frequently amplified DNA sequences included regions in chromosomes 12q(10%), 4q12(7%) and 1q32.1(4%). Based on their gene amplification profiles, glioblastomas were subdivided into: i) tumors with no gene amplification (55%); ii) tumors with chromosome 7p/EGFR gene amplification (with or without amplification of other chromosomal regions) (38%); and iii) glioblastoma multiforme with a single (11%) or multiple (6%) amplified DNA sequences in chromosomal regions other than chromosome 7p. From the prognostic point of view, these amplification profiles showed a significant impact on overall survival of glioblastoma multiforme patients (p>0.001). Based on these gene amplification profiles, a risk-stratification scoring system was built for prognostic stratification of glioblastoma which might be easily implemented in routine diagnostics, and potentially contribute to improved patient management.

7.
Neurocirugia (Astur) ; 28(4): 176-182, 2017.
Artigo em Espanhol | MEDLINE | ID: mdl-28242156

RESUMO

OBJECT: The aim of this study is to assess if the recurrence rates and recurrence/progression-free survivals (RFS) are different after Simpson's grades I, II, III and IV resections in World Health Organization (WHO) grade I meningiomas. MATERIAL AND METHODS: A retrospective review was conducted on the data of patients who underwent surgical treatment of WHO grade I meningiomas located in convexity, falx/parasagittal, and skull base (anterior/media/posterior) between June 1991 and December 2011. In Simpson's grade IV resections, surgical treatment was supplemented with radiotherapy/radiosurgery on the tumour remains. A comparison was made on the recurrence rates and RFSs between Simpson's grades I, II, III, and IV resections, both overall and in tumour subsets according to their location. RESULTS: A total of 208 meningiomas were included in this study. There were no significant differences in recurrence rates and RFSs between Simpson's grades I, II, III, and IV. No significant differences were noted between the different degrees of Simpson in any of the location groups. In convexity meningiomas, the recurrence rates were 7% and 33% in Simpson's grades I and III resections, respectively (P=.131). CONCLUSIONS: It has been shown that the rates of tumour control in meningiomas are not related to Simpson grades. In falx/parasagittal and skull base meningiomas, more aggressive attempts of tumour resection must be balanced against the risks of damaging critical neurovascular structures. In convexity meningiomas, a Simpson's grade I resection should be attempted first.


Assuntos
Neoplasias Meníngeas/cirurgia , Meningioma/cirurgia , Gradação de Tumores/métodos , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Neoplasias Meníngeas/patologia , Meningioma/patologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Estudos Retrospectivos
8.
World Neurosurg ; 96: 483-488, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27637164

RESUMO

BACKGROUND: Since 1957, the Simpson grading system has been considered a predictive system for meningioma recurrence. However, since then, surgical equipment and neurosurgical technique have developed extensively, so this grading system should be re-evaluated. This study aims to assess if the recurrence rate and recurrence-free survival (RFS) are different after Simpson grade I, II, and III resections in World Health Organization (WHO) grade I meningiomas. METHODS: We retrospectively reviewed the data of patients who underwent surgical treatment of WHO grade I meningiomas located in the convexity (group 1), falx/parasagittal (group 2), skull base, and tentorium (group 3) between June 1991 and December 2011. We compared the recurrence rates and RFSs between Simpson grade I, II, and III resections in both overall cases and tumor subsets according to their localization. RESULTS: A total of 224 meningiomas were included in this study. There were no significant differences in recurrence rates and RFSs between Simpson grades I, II, and III. In each of the location groups, no significant differences were noted between the different degrees of Simpson. CONCLUSIONS: We have shown that complete resection of WHO grade I meningiomas achieves excellent tumor control, regardless of Simpson grades. More aggressive attempts at tumor resection (ie, Simpson grade I) must be balanced against the risks of removing dura or damaging critical neurovascular structures.


Assuntos
Neoplasias Meníngeas/diagnóstico , Neoplasias Meníngeas/cirurgia , Meningioma/diagnóstico , Meningioma/cirurgia , Procedimentos Neurocirúrgicos/métodos , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de Tempo , Organização Mundial da Saúde
9.
Brain Behav Immun ; 53: 1-15, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26216710

RESUMO

Tumor-infiltrating immune cells are part of a complex microenvironment that promotes and/or regulates tumor development and growth. Depending on the type of cells and their functional interactions, immune cells may play a key role in suppressing the tumor or in providing support for tumor growth, with relevant effects on patient behavior. In recent years, important advances have been achieved in the characterization of immune cell infiltrates in central nervous system (CNS) tumors, but their role in tumorigenesis and patient behavior still remain poorly understood. Overall, these studies have shown significant but variable levels of infiltration of CNS tumors by macrophage/microglial cells (TAM) and to a less extent also lymphocytes (particularly T-cells and NK cells, and less frequently also B-cells). Of note, TAM infiltrate gliomas at moderate numbers where they frequently show an immune suppressive phenotype and functional behavior; in contrast, infiltration by TAM may be very pronounced in meningiomas, particularly in cases that carry isolated monosomy 22, where the immune infiltrates also contain greater numbers of cytotoxic T and NK-cells associated with an enhanced anti-tumoral immune response. In line with this, the presence of regulatory T cells, is usually limited to a small fraction of all meningiomas, while frequently found in gliomas. Despite these differences between gliomas and meningiomas, both tumors show heterogeneous levels of infiltration by immune cells with variable functionality. In this review we summarize current knowledge about tumor-infiltrating immune cells in the two most common types of CNS tumors-gliomas and meningiomas-, as well as the role that such immune cells may play in the tumor microenvironment in controlling and/or promoting tumor development, growth and control.


Assuntos
Neoplasias Encefálicas/imunologia , Glioma/imunologia , Neoplasias Meníngeas/imunologia , Meningioma/imunologia , Animais , Linfócitos B/imunologia , Linfócitos B/patologia , Neoplasias Encefálicas/patologia , Citometria de Fluxo , Glioma/metabolismo , Glioma/patologia , Humanos , Linfócitos/imunologia , Linfócitos/patologia , Macrófagos/imunologia , Macrófagos/patologia , Neoplasias Meníngeas/metabolismo , Meningioma/metabolismo , Meningioma/patologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/patologia
10.
Semina cienc. biol. saude ; 36(2): 67-74, jul.-dez. 2015. tab, graf
Artigo em Português | LILACS | ID: lil-785307

RESUMO

Objetivo: estabelecer a frequência do hiperparatireoidismo secundário entre pacientes em terapia renal substitutiva em serviço de nefrologia do sudeste do Pará (Brasil).Métodos: estudo do tipo transversal retrospectivo e descritivo realizado com levantamento de dados em sistema eletrônico de prontuários referentes ao primeiro semestre de 2014.Resultados: foram analisados dados de 108 pacientes, com média de idade de 47,8 ± 12,0 anos (20-65), sendo 64 (59,3%) do sexo masculino. A frequência de hiperparatireoidismo secundário foi de 57,4%, correspondendo a um total de 62 pacientes com paratormônio acima de 300 pg/ml. Um nível de paratormônio superior a 1000 pg/ml foi encontrado em 12,0% (n=13) da amostra. Conclusão: a ocorrência de hiperparatireoidismo secundário encontrada foi similar a outros estudos retrospectivos já publicados. Este levantamento de dados pode colaborar para melhorar o planejamento da assistência a pacientes em diálise.


Objective: to establish the frequency of secondary hyperparathyroidism on renal replacement therapy patients on the nephrology service of southeast Para (Brazil). Methods: retrospective cross-sectional survey based on available electronic medical records data referring to the first semester of 2014.Results: data from 108 patients with an average age of 47.8 ± 12.0 years (20-65) were analyzed, 64 patients (59.3%) were male. The frequency of secondary hyperparathyroidism was 57.4%, corresponding to a total of 62 patients with parathyroid hormone above 300 pg/ml. Parathyroid hormone levels greaterthan 1000 pg/ml were found in 12.0% (n=13) of the sample. Conclusion: the occurrence of secondary hyperparathyroidism was similar to other retrospective studies published. This data collection can contribute to improve the assistance program for dialysis patients.


Assuntos
Humanos , Masculino , Feminino , Adulto , Diálise Renal , Hiperparatireoidismo Secundário , Hormônio Paratireóideo , Insuficiência Renal Crônica
11.
Oncotarget ; 6(13): 10671-88, 2015 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-25965831

RESUMO

Meningiomas are usually considered to be benign central nervous system tumors; however, they show heterogenous clinical, histolopathological and cytogenetic features associated with a variable outcome. In recent years important advances have been achieved in the identification of the genetic/molecular alterations of meningiomas and the signaling pathways involved. Thus, monosomy 22, which is often associated with mutations of the NF2 gene, has emerged as the most frequent alteration of meningiomas; in addition, several other genes (e.g., AKT1, KLF4, TRAF7, SMO) and chromosomes have been found to be recurrently altered often in association with more complex karyotypes and involvement of multiple signaling pathways. Here we review the current knowledge about the most relevant genes involved and the signaling pathways targeted by such alterations. In addition, we summarize those proposals that have been made so far for classification and prognostic stratification of meningiomas based on their genetic/genomic features.


Assuntos
Predisposição Genética para Doença/genética , Neoplasias Meníngeas/genética , Meningioma/genética , Neurofibromina 2/genética , Transdução de Sinais/genética , Cromossomos Humanos Par 22/genética , Humanos , Fator 4 Semelhante a Kruppel , Neoplasias Meníngeas/patologia , Meningioma/patologia , Modelos Genéticos , Monossomia
12.
Neuropathol Appl Neurobiol ; 41(3): 319-32, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24612434

RESUMO

AIMS: Limited information exists about the impact of cytogenetic alterations on the protein expression profiles of individual meningioma cells and their association with the clinicohistopathological characteristics of the disease. The aim of this study is to investigate the potential association between the immunophenotypic profile of single meningioma cells and the most relevant features of the tumour. METHODS: Multiparameter flow cytometry (MFC) was used to evaluate the immunophenotypic profile of tumour cells (n = 51 patients) and the Affymetrix U133A chip was applied for the analysis of the gene expression profile (n = 40) of meningioma samples, cytogenetically characterized by interphase fluorescence in situ hybridization. RESULTS: Overall, a close association between the pattern of protein expression and the cytogenetic profile of tumour cells was found. Thus, diploid tumours displayed higher levels of expression of the CD55 complement regulatory protein, tumours carrying isolated monosomy 22/del(22q) showed greater levels of bcl2 and PDGFRß and meningiomas carrying complex karyotypes displayed a greater proliferation index and decreased expression of the CD13 ectoenzyme, the CD9 and CD81 tetraspanins, and the Her2/neu growth factor receptor. From the clinical point of view, higher expression of CD53 and CD44 was associated with a poorer outcome. CONCLUSIONS: Here we show that the protein expression profile of individual meningioma cells is closely associated with tumour cytogenetics, which may reflect the involvement of different signalling pathways in the distinct cytogenetic subgroups of meningiomas, with specific immunophenotypic profiles also translating into a different tumour clinical behaviour.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/metabolismo , Meningioma/genética , Meningioma/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Separação Celular , Análise Citogenética , Feminino , Citometria de Fluxo , Perfilação da Expressão Gênica , Humanos , Hibridização in Situ Fluorescente , Masculino , Neoplasias Meníngeas/patologia , Meningioma/patologia , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Adulto Jovem
13.
Neuro Oncol ; 16(5): 735-47, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24536048

RESUMO

BACKGROUND: Tumor recurrence remains the major clinical complication of meningiomas, the majority of recurrences occurring among WHO grade I/benign tumors. In the present study, we propose a new scoring system for the prognostic stratification of meningioma patients based on analysis of a large series of meningiomas followed for a median of >5 years. METHODS: Tumor cytogenetics were systematically investigated by interphase fluorescence in situ hybridization in 302 meningioma samples, and the proposed classification was further validated in an independent series of cases (n = 132) analyzed by high-density (500K) single-nucleotide polymorphism (SNP) arrays. RESULTS: Overall, we found an adverse impact on patient relapse-free survival (RFS) for males, presence of brain edema, younger patients (<55 years), tumor size >50 mm, tumor localization at intraventricular and anterior cranial base areas, WHO grade II/III meningiomas, and complex karyotypes; the latter 5 variables showed an independent predictive value in multivariate analysis. Based on these parameters, a prognostic score was established for each individual case, and patients were stratified into 4 risk categories with significantly different (P < .001) outcomes. These included a good prognosis group, consisting of approximately 20% of cases, that showed a RFS of 100% ± 0% at 10 years and a very poor-prognosis group with a RFS rate of 0% ± 0% at 10 years. The prognostic impact of the scoring system proposed here was also retained when WHO grade I cases were considered separately (P < .001). CONCLUSIONS: Based on this risk-stratification classification, different strategies may be adopted for follow-up, and eventually also for treatment, of meningioma patients at different risks for relapse.


Assuntos
Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Meningioma/diagnóstico , Meningioma/genética , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/patologia , Criança , Análise Citogenética , Feminino , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Masculino , Meningioma/patologia , Pessoa de Meia-Idade , Gradação de Tumores , Fatores de Risco , Análise de Sobrevida , Adulto Jovem
14.
BMC Med Genet ; 14: 114, 2013 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-24171707

RESUMO

BACKGROUND: Meningioma was the first solid tumor shown to contain a recurrent genetic alteration e.g. monosomy 22/del(22q), NF2 being the most relevant gene involved. Although monosomy 22/del(22q) is present in half of all meningiomas, and meningiomas frequently carry NF2 mutations, no study has been reported so far in which both alterations are simultaneously assessed and correlated with the features of the disease. METHODS: Here, we analyzed the frequency of both copy number changes involving chromosome 22 and NF2 mutations in 20 sporadic meningiomas using high-density SNP-arrays, interphase-FISH and PCR techniques. RESULTS: Our results show a significant frequency of NF2 mutations (6/20 patients, 30%), most of which (5/6) had not been previously reported in sporadic meningiomas. NF2 mutations involved five different exons and led to a truncated protein (p.Leu163CysfsX46, p.Phe62LeufsX61, p.Asp281MetfsX15, p.Phe285LeufsX11, p.Gln389ArgfsX37) and an in frame deletion of Phe119. Interestingly, all NF2 mutated cases were menopausal women with monosomy 22 but not del(22q). CONCLUSIONS: These results confirm and extend on previous observations about the high frequency and heterogeneity of NF2 mutations in sporadic meningiomas and indicate they could be restricted to a well-defined cytogenetic and clinical subgroup of menopausal women. Further studies in large series of patients are required to confirm our observations.


Assuntos
Cromossomos Humanos Par 22 , Neoplasias Meníngeas/genética , Meningioma/genética , Monossomia/genética , Neurofibromina 2/genética , Idoso , Deleção Cromossômica , Éxons , Feminino , Dosagem de Genes , Humanos , Perda de Heterozigosidade , Masculino , Menopausa , Pessoa de Meia-Idade , Mutação , Taxa de Mutação , Polimorfismo de Nucleotídeo Único
15.
PLoS One ; 8(10): e74798, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24098347

RESUMO

Meningiomas contain highly variable levels of infiltrating tissue macrophages (TiMa) and other immune cells. In this study we investigated the potential association between the number and immunophenotype of inflammatory and other immune cells infiltrating the tumor as evaluated by multiparameter flow cytometry, and the clinico-biological, cytogenetic and gene expression profile (GEP) of 75 meningioma patients. Overall, our results showed a close association between the amount and cellular composition of the inflammatory and other immune cell infiltrates and the cytogenetic profile of the tumors. Notably, tumors with isolated monosomy 22/del(22q) showed greater numbers of TiMa, NK cells and (recently)-activated CD69(+) lymphocytes versus meningiomas with diploid and complex karyotypes. In addition, in the former cytogenetic subgroup of meningiomas, tumor-infiltrating TiMa also showed a more activated and functionally mature phenotype, as reflected by a greater fraction of CD69(+), CD63(+), CD16(+) and CD33(+) cells. GEP at the mRNA level showed a unique GEP among meningiomas with an isolated monosomy 22/del(22q) versus all other cases, which consisted of increased expression of genes involved in inflammatory/immune response, associated with an M1 TiMa phenotype. Altogether, these results suggest that loss of expression of specific genes coded in chromosome 22 (e.g. MIF) is closely associated with an increased homing and potentially also anti-tumoral effect of TiMa, which could contribute to explain the better outcome of this specific good-prognosis cytogenetic subgroup of meningiomas.


Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 22/genética , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/imunologia , Meningioma/genética , Meningioma/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Células Apresentadoras de Antígenos/imunologia , Feminino , Humanos , Inflamação/imunologia , Cariótipo , Linfócitos/imunologia , Masculino , Pessoa de Meia-Idade , Transcriptoma , Adulto Jovem
16.
Acta Otolaryngol ; 133(5): 475-80, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23317346

RESUMO

CONCLUSIONS: The degree of caloric weakness before surgery influences faster or slower recovery of patients undergoing vestibular schwannoma surgery. The Dizziness Handicap Inventory (DHI) is a good index to show the recovery of patients as it relates directly to an improvement or not of the subjective visual vertical (SVV). OBJECTIVE: To evaluate the process of recovery of patients as measured by the SVV and the DHI after surgical removal of vestibular schwannoma. METHODS: We studied 24 consecutive patients of the University Hospital of Salamanca who underwent vestibular schwannoma surgery. We assessed age, tumour size, degree of canalicular weakness and preoperative SVV, and their relationship with DHI and SVV at discharge and also at 1, 3 and 6 months postoperatively. RESULTS: Patients with lesser degrees of caloric weakness took longer to normalize SVV than those with a higher caloric weakness before surgery (p < 0.05). There was a significant correlation between DHI and improvements in SVV with time. The differences disappeared in 6 months where all patients, with greater or lesser degree of caloric weakness, had the same results.


Assuntos
Neuroma Acústico/cirurgia , Percepção Visual/fisiologia , Adulto , Estudos de Coortes , Avaliação da Deficiência , Tontura/etiologia , Tontura/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neuroma Acústico/complicações , Neuroma Acústico/fisiopatologia , Equilíbrio Postural/fisiologia , Recuperação de Função Fisiológica/fisiologia , Fatores de Tempo , Testes de Função Vestibular
17.
Am J Pathol ; 181(5): 1749-61, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22982440

RESUMO

Meningiomas are primary tumors of the central nervous system composed of both neoplastic and other infiltrating cells. We determined the cellular composition of 51 meningioma samples by multiparameter flow cytometric (MFC) immunophenotyping and investigated the potential relationship between mRNA and protein expression levels of neoplastic cells. For immunophenotypic, morphologic, and cytogenetic characterization of individual cell populations, a large panel of markers was used together with phagocytic/endocytic functional assays and MFC sorting. Overall, our results revealed coexistence of CD45(-) neoplastic cells and CD45(+) immune infiltrating cells in all meningiomas. Infiltrating cells included tissue macrophages, with an HLA-DR(+)CD14(+)CD45(+)CD68(+)CD16(-/+)CD33(-/+) phenotype and high phagocytic/endocytic activity, and a small proportion of cytotoxic lymphocytes (mostly T CD8(+) and natural killer cells). Tumor cells expressed multiple cell adhesion proteins, tetraspanins, HLA-I/HLA-DR molecules, complement regulatory proteins, cell surface ectoenzymes, and growth factor receptors. Noteworthy, the relationship between mRNA and protein levels was variable, depending on the proteins evaluated and the level of infiltration by immune cells. In summary, our results indicate that MFC immunophenotyping provides a reliable tool for the characterization of the patterns of protein expression of different cell populations coexisting in meningioma samples, with a more accurate measure of gene expression profiles of tumor cells at the functional/protein level than conventional mRNA microarray, independently of the degree of infiltration of the tumor by immune cells.


Assuntos
Imunofenotipagem , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/patologia , Neoplasias Meníngeas/imunologia , Neoplasias Meníngeas/patologia , Meningioma/imunologia , Meningioma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Compartimento Celular , Feminino , Citometria de Fluxo , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Linfócitos do Interstício Tumoral/metabolismo , Masculino , Neoplasias Meníngeas/genética , Meningioma/genética , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Fagocitose , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
18.
Genes Chromosomes Cancer ; 51(6): 606-17, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22371336

RESUMO

Despite recent advances in the identification of the cytogenetic profiles of meningiomas, a significant group of tumors still show normal karyotypes or few chromosomal changes. The authors analyzed the cytogenetic profile of 50 meningiomas using fluorescence in situ hybridization and high-density (500 K) single nucleotide polymorphism (SNP) arrays. Our results confirm that del(22q) (52%) and del(1p) (16%) (common deleted regions: 22q11.21-22q13.3. and 1p31.2-p36.33) are the most frequent alterations. Additionally, recurrent monosomy 14 (8%), del(6q) (10%), del(7p) (10%), and del(19q) (4%) were observed, while copy number patterns consistent with recurrent chromosomal gains, gene amplification, and copy number neutral loss of heterozygosity (cnLOH) were either absent or rare. Based on their overall SNP profiles, meningiomas could be classified into: (i) diploid cases, (ii) meningiomas with a single chromosomal change [e.g., monosomy 22/del(22q)] and (iii) tumors with ≥2 altered chromosomes. In summary, our results confirm and extend on previous observations showing that the most recurrent chromosomal abnormalities in meningiomas correspond to chromosome losses localized in chromosomes 1, 22 and less frequently in chromosomes 6, 7, 14, and 19, while chromosomal gains and cnLOH are restricted to a small proportion of cases. Finally, a set of cancer-associated candidate genes associated with the TP53, MYC, CASP3, HDAC1, and TERT signaling pathways was identified, in cases with coexisting monosomy 14 and del(1p).


Assuntos
Deleção Cromossômica , Neoplasias Meníngeas/genética , Meningioma/genética , Adulto , Idoso , Feminino , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Polimorfismo de Nucleotídeo Único , Transdução de Sinais
19.
Brain Pathol ; 19(3): 409-20, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18637901

RESUMO

Cytogenetic analysis is a powerful tool for predicting recurrence in meningiomas, even among histologically benign/grade I tumors. Despite this, no study has been reported in which the impact of tumor cytogenetics on the gene expression profiles (GEP) has been analyzed in meningiomas. Here, we analyzed the GEP of 47 tumors and correlated them with the most clinical relevant cytogenetic subgroups of meningiomas, as confirmed through the analysis of 172 patients. Additionally three normal meningeal samples were also studied. Overall, our results show a clear association between the clinically relevant cytogenetic subgroups of meningiomas including diploid tumors (n = 18), isolated -22/22q- (n = 12), del(1p36) alone (n = 4) and complex karyotypes associated with del(1p36) and/or -14q (n = 13) and their GEP. Accordingly, based on the expression of 85 genes (40 of which were coded in the altered chromosomes used for patient stratification) the cytogenetic class of the tumor could be predicted with an error of <1%, a clear association being found between the GEP and patient outcome (P = 0.03) but not tumor histopathology. In summary, we show a clear association between GEP of neoplastic cells and clinically relevant cytogenetic subgroups of meningiomas.


Assuntos
Análise Citogenética , Perfilação da Expressão Gênica , Neoplasias Meníngeas/genética , Meningioma/genética , Recidiva Local de Neoplasia/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Hibridização in Situ Fluorescente , Estimativa de Kaplan-Meier , Masculino , Neoplasias Meníngeas/mortalidade , Neoplasias Meníngeas/patologia , Meningioma/mortalidade , Meningioma/patologia , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Resultado do Tratamento , Adulto Jovem
20.
J Child Neurol ; 23(9): 1058-61, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18827270

RESUMO

We report a divergent ependymal tumor of the posterior fossa (ependymoblastoma/anaplastic ependymoma) observed in an 8-year-old boy. The tumor showed the histological pattern typical of an ependymoblastoma (tubular-papillary fetaloid architecture with stratification of the tumor cells) next to areas in which findings typical of an anaplastic ependymoma were detected. The immunohistochemical study confirmed our diagnostic suspicion, allowing us to establish a differential diagnosis with other entities such as medulloblastoma, medulloepithelioma, atypical rhabdoid/teratoid tumor, or metastases.


Assuntos
Neoplasias do Ventrículo Cerebral/patologia , Ependimoma/patologia , Quarto Ventrículo/patologia , Neoplasias Infratentoriais/patologia , Fatores Etários , Idade de Início , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Tronco Encefálico/patologia , Tronco Encefálico/fisiopatologia , Cerebelo/patologia , Cerebelo/fisiopatologia , Neoplasias do Ventrículo Cerebral/fisiopatologia , Criança , Diagnóstico Diferencial , Ependimoma/fisiopatologia , Feminino , Quarto Ventrículo/fisiopatologia , Cefaleia/etiologia , Humanos , Neoplasias Infratentoriais/fisiopatologia , Imageamento por Ressonância Magnética , Meduloblastoma/diagnóstico , Procedimentos Neurocirúrgicos , Resultado do Tratamento , Vômito/etiologia
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