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1.
Zhonghua Bing Li Xue Za Zhi ; 48(3): 192-198, 2019 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-30831644

RESUMO

Objective: To analyze the clinicopathological characteristics and prognosis of diffuse midline glioma (DMG) with H3K27M mutation. Methods: Thirty cases of DMG were collected in Guangdong Sanjiu Brain Hospital from October 2016 to May 2018. The patients' clinicopathological data including age, tumor site and histological grade, treatment and follow-up data were collected and analyzed. Results: There were 21 males and 9 females, with a mean age of 26 years (range 5-53 years). Fourteen tumors were located in thalamus, 12 in brainstem (one involved both thalamus and brainstem), and one each in hypothalamus, fourth ventricle, and sellar region, respectively. Two cases presented as diffuse intracranial lesions. Three cases (10.0%) were of WHO grade Ⅰ, 10 cases (33.3%) were grade Ⅱ, eight cases (26.7%) were grade Ⅲ, and nine cases (30.0%) were grade Ⅳ.All patients with gradeⅠ tumors were older than 20 years. Histologically, all were pilocytic astrocytoma-like. Immunohistochemical staining demonstrated that all tumors were IDH1 negative. Twenty-eight tumors showed diffuse expression of H3K27M, and two showed focal expression. Twenty-one tumors(100.0%, 21/21) showed absent expression of H3K27me3. Sixteen tumors (57.1%, 16/28) showed strongly positive expression of p53, and ATRX was negative in eight tumors (38.1%, 8/21). The Ki-67 proliferation index ranged from 5% to 40%. Eight cases (including two cases of H3K27M expression of individual cells) showed K27M mutation in H3F3A gene. Intracranial and spinal cord dissemination occurred in six cases (20.0%, 6/30). Median progression-free survival (PFS) was 9.5 months and median overall survival (OS) was 34 months. Mean PFS was 11.2 months and mean OS was 24.3 months. Compared with adults (>20 years old), children/adolescents (no more than 20 years old) had significantly shorter median OS (8 months vs. 34 months, P=0.013). There was no significant difference in PFS and OS between DMGs located in the brain stem/thalamus and other sites within midline (P>0.05). There was no significant difference in PFS and OS between WHO grade ⅠDMGs and WHO grade Ⅱ-Ⅳ DMGs (P>0.05). Conclusions: DMGs occur more commonly in children and adolescents with male predominance. DMGs present with WHO Ⅰ-Ⅳ tumors morphologically, and pilocytic astrocytoma-like lesions with WHO Ⅰ are more common in adults. Expression of H3K27M but not H3K27me3 is helpful for diagnosis of DMG. The prognosis of children/adolescents is significantly worse than that of adults, whereas histological grade and tumor location do not affect prognosis.


Assuntos
Neoplasias Encefálicas/enzimologia , Glioma/enzimologia , Histona Desmetilases com o Domínio Jumonji/genética , Mutação , Adolescente , Adulto , Fatores Etários , Astrocitoma/química , Astrocitoma/enzimologia , Astrocitoma/mortalidade , Astrocitoma/patologia , Neoplasias Encefálicas/química , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Neoplasias do Tronco Encefálico/química , Neoplasias do Tronco Encefálico/enzimologia , Neoplasias do Tronco Encefálico/patologia , Criança , Pré-Escolar , Feminino , Glioma/química , Glioma/mortalidade , Glioma/patologia , Histonas/genética , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Tálamo , Adulto Jovem
2.
Eur Rev Med Pharmacol Sci ; 21(16): 3611-3616, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28925495

RESUMO

OBJECTIVE: To investigate the activation of the BMP7 and laminin pathway is associated with glioma cell proliferation and differentiation. PATIENTS AND METHODS: We enrolled 65 patients with primary operable glioma. Laminin and BMP7 protein expression and its subcellular localization were studied by immunofluorescence. RESULTS: We detected a higher level of BMP7 expression in glioma tissue in patients with a lower grade of glioma who had a lower eosinophil count. Compared to patients with a higher grade of glioma, we observed a lower level of laminin expression in patients with a lower grade of glioma. CONCLUSIONS: Our data indicated a potential link between eosinophil counts and the expression levels of laminin and BMP7 in glioma differentiation.


Assuntos
Astrocitoma/patologia , Proteína Morfogenética Óssea 7/análise , Neoplasias Encefálicas/patologia , Laminina/análise , Adulto , Astrocitoma/sangue , Astrocitoma/química , Neoplasias Encefálicas/sangue , Neoplasias Encefálicas/química , Diferenciação Celular , Eosinófilos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
3.
Neurosci Lett ; 634: 160-167, 2016 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-27751786

RESUMO

Astrocytes are multifunctional glial cells that actively participate in synaptic plasticity in health and disease. Little is known about molecular interactions between neurons and glial cells that result in synaptic stability or elimination. In this sense, the main histocompatibility complex of class I (MHC I) has been shown to play a role in the synaptic plasticity process during development and after lesion of the CNS. MHC I levels in neurons appear to be influenced by astrocyte secreted molecules, which may generate endoplasmic reticulum stress. In vitro studies are of relevance since cell contact can be avoided by the use of astrocyte conditioned medium, allowing investigation of soluble factors isolated from cell direct interaction. Thus, we investigated synaptic preservation by synaptophysin and MHC I immunolabeling in PC12 neuron-like cells exposed to NG97 astroglioma conditioned medium (CM). For that, PC12 cells were cultured and differentiated into neuron-like profile with nerve growth factor. MHC I was induced with interferon beta treatment (IFN), and the effects were compared to PC12 exposure to NG97 CM. Overall, the results show that NG97 CM increases, more than IFN alone, the expression of MHC I, negatively influencing synaptic stability. This indicates that glial soluble factors influence synapse elimination, compatible to in vivo synaptic stripping process, in a cell contact independent fashion. In turn, our results indicate that deleterious effects of astroglioma are not only restricted to rapid growth ratio of the tumor, but also correlated with secretion of stress-related molecules that directly affect neuronal networks.


Assuntos
Astrócitos/metabolismo , Astrocitoma/química , Fatores Biológicos/metabolismo , Meios de Cultivo Condicionados/química , Antígenos de Histocompatibilidade Classe I/metabolismo , Neurônios/metabolismo , Sinapses/fisiologia , Animais , Astrócitos/química , Fatores Biológicos/química , Contagem de Células , Interferon beta/farmacologia , Plasticidade Neuronal , Células PC12 , Ratos , Sinaptofisina/metabolismo , Regulação para Cima
4.
J BUON ; 21(1): 191-8, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27061548

RESUMO

PURPOSE: This study aimed to investigate the expression and clinical significance of nestin in human astrocytic tumors. METHODS: Indirect immunofluorescent staining and flow cytometry were used to quantitatively detect the nestin content in 35 specimens, including 3 normal brain tissues, 29 astrocytic tumor (AT) tissues, and 3 peritumoral tissues. RESULTS: In normal brain tissues, nestin expression was extremely low. Nestin expression was significantly positively correlated with the histological grade of astrocytic tumors (p<0.05, rs=0.83). Nestin content in the peritumoral tissues was between the levels of nestin in tumor tissue and in normal brain tissue (p<0.01). Nestin expression was unrelated to the patient's gender, age, tumor location, size, etc. (p>0.05). CONCLUSION: The application of flow cytometry in the determination of nestin content could improve the accuracy of early cancer diagnosis. This method would be helpful for developing a reference range that is closely related to the pathological grading of ATs through routine assessments of nestin in many patients. Additionally, through examining nestin levels in peritumoral tissues, the invasiveness of ATs can be clarified.


Assuntos
Astrocitoma/patologia , Neoplasias Encefálicas/patologia , Nestina/análise , Adolescente , Adulto , Idoso , Astrocitoma/química , Química Encefálica , Neoplasias Encefálicas/química , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade
5.
J Clin Pathol ; 69(1): 26-34, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26188054

RESUMO

AIMS: The limitations of the current WHO classification of astrocytomas call for a sustained effort to improve diagnostic and prognostic accuracy. The relationship between tumour growth and clinical outcome suggests that proliferative activity should be examined. The objective of this study was to evaluate the diagnostic and prognostic value of the proliferation markers mitosin and phosphohistone H3 (pHH3) in infiltrative astrocytomas WHO grades II and III and compare the findings with mitotic count and Ki-67/MiB-1 immunostaining. METHODS: Fifty-nine and thirty-three infiltrative astrocytomas WHO grades II and III, respectively, were immunostained with the proliferation markers mitosin and pHH3 using standard immunohistochemical procedures. The expression was quantified as a proliferative index (PI) and statistically evaluated with Spearman's rank correlation test, Wilcoxon-Mann-Whitney U test, and univariable and multivariable COX regression survival analyses. RESULTS: Significant positive correlations were found between these proliferation markers. The number of mitoses, pHH3 mitotic figures (MFs), the Ki-67/MiB-1 PI and the mitosin PI were greater in WHOgrade III anaplastic astrocytomas compared to WHO grade II diffuse astrocytomas, while pHH3 PI only showed a trend. All proliferation markers were associated with poorer prognosis, but mitotic count was not. Ki-67/MiB-1, mitosin and pHH3 MF achieved statistical significance in the univariable analyses of both time to relapse (TTR) and overall survival (OS). Only mitosin remained significant in both multivariable analyses. pHH3 was significant in the multivariable analysis of OS but not of TTR. Clinical factors including age, extent of surgical resection and WHO performance status were also significantly correlated with survival. CONCLUSIONS: In conclusion, mitosin and pHH3 immunostaining have prognostic and diagnostic value in the clinical assessment of patients with infiltrative astrocytomas. The inclusion of proliferation markers in a layered diagnosis should be considered in the upcoming revision of the WHO classification system.


Assuntos
Astrocitoma/química , Biomarcadores Tumorais/análise , Neoplasias Encefálicas/química , Proteínas Cromossômicas não Histona/análise , Histonas/análise , Proteínas dos Microfilamentos/análise , Adulto , Idoso , Astrocitoma/classificação , Astrocitoma/mortalidade , Astrocitoma/patologia , Astrocitoma/terapia , Neoplasias Encefálicas/classificação , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/terapia , Proliferação de Células , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Antígeno Ki-67/análise , Masculino , Pessoa de Meia-Idade , Mitose , Índice Mitótico , Análise Multivariada , Gradação de Tumores , Recidiva Local de Neoplasia , Fosforilação , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
6.
J Am Soc Mass Spectrom ; 26(12): 2062-76, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26450359

RESUMO

Protein tyrosine nitration is involved in the pathogenesis of highly fatal astrocytomas, a type of brain cancer. To understand the molecular mechanisms of astrocytomas and to discover new biomarkers/therapeutic targets, we sought to identify nitroproteins in human astrocytoma tissue. Anti-nitrotyrosine immunoreaction-positive proteins from a high-grade astrocytoma tissue were detected with two-dimensional gel electrophoresis (2DGE)-based nitrotyrosine immunoblots, and identified with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Fifty-seven nitrotyrosine immunopositive protein spots were detected. A total of 870 proteins (nitrated and non-nitrated) in nitrotyrosine-immunopositive 2D gel spots were identified, and 18 nitroproteins and their 20 nitrotyrosine sites were identified with MS/MS analysis. These nitroproteins participate in multiple processes, including drug-resistance, signal transduction, cytoskeleton, transcription and translation, cell proliferation and apoptosis, immune response, phenotypic dedifferentiation, cell migration, and metastasis. Among those nitroproteins that might play a role in astrocytomas was nitro-sorcin, which is involved in drug resistance and metastasis and might play a role in the spread and treatment of an astrocytoma. Semiquantitative immune-based measurements of different sorcin expressions were found among different grades of astrocytomas relative to controls, and a semiquantitative increased nitration level in high-grade astrocytoma relative to control. Nitro-ß-tubulin functions in cytoskeleton and cell migration. Semiquantitative immunoreactivity of ß-tubulin showed increased expression among different grades of astrocytomas relative to controls and semiquantitatively increased nitration level in high-grade astrocytoma relative to control. Each nitroprotein was rationalized and related to the corresponding functional system to provide new insights into tyrosine nitration and its potential role in the pathogenesis of astrocytoma formation. Graphical Abstract ᅟ.


Assuntos
Astrocitoma/química , Neoplasias Encefálicas/química , Encéfalo/patologia , Eletroforese em Gel Bidimensional/métodos , Proteínas/química , Espectrometria de Massas em Tandem/métodos , Tirosina/análogos & derivados , Adolescente , Adulto , Idoso , Sequência de Aminoácidos , Astrocitoma/patologia , Western Blotting , Química Encefálica , Neoplasias Encefálicas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Tirosina/análise
7.
Int J Clin Exp Pathol ; 8(7): 8545-50, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26339431

RESUMO

Malignant ectomesenchymoma is a rare tumor that contains both ectodermal and mesenchymal elements. So far, only 7 patients with a manifestation in the cerebrum (with confirmed clinicopathological data) have been reported. A 4-year-old girl was present at our hospital with a 3-week history of intermittent sudden dizzy with no apparent cause. MRI showed an irregular enhanced lesion in the left frontal-parietal lobe and lateral ventricle with peripheral gadolinium-enhancement with a significant surrounding edema. Total removal of the tumor was performed. Histological examination of the resected tumor revealed a mixed astrocytoma and anaplastic ependymoma component with undifferentiated mesenchymal spindle cell component. Generally speaking, the main malignant part in most cases of malignant ectomesenchymoma (MEM) is the mesenchymal component. In the present case, the malignant component was both in the mesenchymal and ectodermal part. In particular, the mesenchymal part was mainly composed of spindle cells, and the ectodermal part primarily consisted of gliomatous component and anaplastic ependymoma component. The patient was then treated with chemotherapy and as regard to the prognosis, there was no evidence of tumor recurrence at the 5 months' follow-up. The long term follow-up is still in progress.


Assuntos
Astrocitoma/patologia , Neoplasias Encefálicas/patologia , Cérebro/patologia , Ependimoma/patologia , Neoplasias Complexas Mistas/patologia , Astrocitoma/química , Astrocitoma/cirurgia , Biomarcadores Tumorais/análise , Biópsia , Neoplasias Encefálicas/química , Neoplasias Encefálicas/cirurgia , Cérebro/química , Cérebro/cirurgia , Quimioterapia Adjuvante , Pré-Escolar , Ependimoma/química , Ependimoma/cirurgia , Feminino , Humanos , Imuno-Histoquímica , Imagem por Ressonância Magnética , Neoplasias Complexas Mistas/química , Neoplasias Complexas Mistas/cirurgia , Fatores de Tempo , Resultado do Tratamento
8.
Int J Clin Exp Pathol ; 8(6): 7570-4, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26261671

RESUMO

Pleomorphic xanthoastrocytoma (PXA) is an uncommon tumor of young adults that typically occurs supratentorially. It is generally considered to be a low-grade, circumscribed tumor that when treated by surgical resection has a relatively favorable outcome. Cases of cerebellar PXA are rare, and those associated with neurofibromatosis type 1 (NF1) are even less common, with only 2 cases reported to date. We present herein a third case of PXA-NF1 with unusual features. A 33-year-old woman presented with a history of headache. Her medical and family history was significant for NF1. Brain MRI revealed a 3.4 cm ill-defined lesion with a gyriform enhancing pattern in the left cerebellum, superficially mimicking Lhermitte-Duclos disease. The patient underwent a gross total resection of the lesion and had an unremarkable postoperative course. While the lesion had histological features typical of "pure" PXA (WHO grade II) it had an unusual growth pattern with thickening of the superficial cerebellar folia and predominant leptomeningeal involvement. No BRAF, IDH-1, or IDH-2 mutation was identified. Three months after surgery, local recurrence was detected, and the patient was treated with radiation therapy. One year after the first surgery, she underwent surgical resection of the recurrent/residual tumor. Histologically, the recurrent tumor showed very similar features to the initially resected tumor, with no anaplastic features. Most cerebellar PXAs have an indolent clinical behavior as do most cerebral PXAs. Whether co-existence of NF1 was a factor in altering the clinical course and biologic behavior of this patient's tumor is currently unknown.


Assuntos
Astrocitoma/patologia , Neoplasias Cerebelares/patologia , Neurofibromatose 1/patologia , Xantomatose/patologia , Adulto , Astrocitoma/química , Astrocitoma/genética , Astrocitoma/cirurgia , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Biópsia , Neoplasias Cerebelares/química , Neoplasias Cerebelares/genética , Neoplasias Cerebelares/cirurgia , Análise Mutacional de DNA , Feminino , Humanos , Imuno-Histoquímica , Imagem por Ressonância Magnética , Mutação , Recidiva Local de Neoplasia , Neurofibromatose 1/genética , Neurofibromatose 1/metabolismo , Neurofibromatose 1/cirurgia , Resultado do Tratamento , Carga Tumoral , Xantomatose/genética , Xantomatose/metabolismo , Xantomatose/cirurgia
9.
PLoS One ; 10(4): e0123607, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25876071

RESUMO

Improved tools for providing specific intraoperative diagnoses could improve patient care. In neurosurgery, intraoperatively differentiating non-operative lesions such as CNS B-cell lymphoma from operative lesions can be challenging, often necessitating immunohistochemical (IHC) procedures which require up to 24-48 hours. Here, we evaluate the feasibility of generating rapid ex vivo specific labeling using a novel lymphoma-specific fluorescent switchable aptamer. Our B-cell lymphoma-specific switchable aptamer produced only low-level fluorescence in its unbound conformation and generated an 8-fold increase in fluorescence once bound to its target on CD20-positive lymphoma cells. The aptamer demonstrated strong binding to B-cell lymphoma cells within 15 minutes of incubation as observed by flow cytometry. We applied the switchable aptamer to ex vivo xenograft tissue harboring B-cell lymphoma and astrocytoma, and within one hour specific visual identification of lymphoma was routinely possible. In this proof-of-concept study in human cell culture and orthotopic xenografts, we conclude that a fluorescent switchable aptamer can provide rapid and specific labeling of B-cell lymphoma, and that developing aptamer-based labeling approaches could simplify tissue staining and drastically reduce time to histopathological diagnoses compared with IHC-based methods. We propose that switchable aptamers could enhance expeditious, accurate intraoperative decision-making.


Assuntos
Aptâmeros de Nucleotídeos/química , Neoplasias do Sistema Nervoso Central/diagnóstico , Linfoma de Células B/diagnóstico , Conformação de Ácido Nucleico , Animais , Astrocitoma/química , Astrocitoma/genética , Astrocitoma/metabolismo , Linhagem Celular Tumoral , Neoplasias do Sistema Nervoso Central/química , Neoplasias do Sistema Nervoso Central/cirurgia , Citometria de Fluxo , Corantes Fluorescentes/química , Fluorometria , Humanos , Período Intraoperatório , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Linfoma de Células B/química , Linfoma de Células B/cirurgia , Microscopia Confocal , Técnicas de Diagnóstico Molecular/métodos , Ratos Nus , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Transplante Heterólogo
10.
Mol Biosyst ; 11(6): 1668-83, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25909245

RESUMO

A top-down/bottom-up integrated proteomic approach based on LC-MS and 2-DE analysis was applied for comparative characterization of medulloblastoma and pilocytic astrocytoma posterior cranial fossa pediatric brain tumor tissues. Although rare, primary brain tumors are the most frequent solid tumors in the pediatric age. Among them the medulloblastoma is the prevalent malignant tumor in childhood while pilocytic astrocytoma is the most common, rarely showing a malignant progression. Due to the limited availability of this kind of sample, the study was applied to pooled tumor tissues for a preliminary investigation. The results showed different proteomic profiles of the two tumors and evidenced interesting differential expression of several proteins and peptides. Top-down proteomics of acid-soluble fractions of brain tumor homogenates ascribed a potential biomarker role of malignancy to ß- and α-thymosins and their truncated proteoforms and to C-terminal truncated (des-GG) ubiquitin, resulting exclusively detected or over-expressed in the highly malignant medulloblastoma. The bottom-up proteomics of the acid-soluble fraction identified several proteins, some of them in common with 2-DE analysis of acid-insoluble pellets. Peroxiredoxin-1, peptidyl-prolyl cis-trans isomerase A, triosephosphate isomerase, pyruvate kinase PKM, tubulin beta and alpha chains, heat shock protein HSP-90-beta and different histones characterized the medulloblastoma while the Ig kappa chain C region, serotransferrin, tubulin beta 2A chain and vimentin the pilocytic astrocytoma. The two proteomic strategies, with their pros and cons, well complemented each other in characterizing the proteome of brain tumor tissues and in disclosing potential disease biomarkers to be validated in a future study on individual samples of both tumor histotypes.


Assuntos
Astrocitoma/química , Neoplasias Encefálicas/química , Meduloblastoma/química , Proteoma/análise , Astrocitoma/metabolismo , Neoplasias Encefálicas/metabolismo , Criança , Pré-Escolar , Humanos , Meduloblastoma/metabolismo , Proteínas/análise , Proteínas/química , Proteínas/metabolismo , Proteoma/química , Proteoma/metabolismo , Proteômica
11.
J Neurosurg Pediatr ; 15(5): 506-9, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25700123

RESUMO

Granular cell astrocytoma (GCA) is a rare type of infiltrative brain tumor with most reported cases occurring in the suprasellar region. A pineal localization is extremely rare, with only 4 previously reported cases in the literature. The authors describe the case of a 16-year-old boy who developed signs of increased intracranial pressure and Parinaud syndrome. Cranial CT and MRI revealed a well-demarcated and enhanced mass in the pineal region accompanied by obstructive hydrocephalus. Subtotal resection was performed via a subtemporal approach. A histological diagnosis of GCA was made. Three years after surgery, the patient was alive and well without adjuvant therapy, and serial MRI showed no signs of progression of a small residual tumor. After a thorough review of the different epidemiological, clinical, and imaging features; treatments; and prognoses of GCAs in other intracranial localizations, the authors analyzed features of this tumor in the pineal region.


Assuntos
Astrocitoma/diagnóstico , Astrocitoma/cirurgia , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/cirurgia , Tumor de Células Granulares/diagnóstico , Tumor de Células Granulares/cirurgia , Hidrocefalia/etiologia , Glândula Pineal , Adolescente , Astrocitoma/química , Astrocitoma/complicações , Astrocitoma/patologia , Biomarcadores Tumorais/análise , Neoplasias Encefálicas/química , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/patologia , Diagnóstico Diferencial , Tumor de Células Granulares/química , Tumor de Células Granulares/complicações , Tumor de Células Granulares/patologia , Cefaleia/etiologia , Humanos , Imagem por Ressonância Magnética , Masculino , Neoplasia Residual/diagnóstico , Glândula Pineal/patologia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Vertigem/etiologia
12.
Neuroradiology ; 57(3): 275-81, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25487356

RESUMO

INTRODUCTION: Hemangioblastomas and pilocytic astrocytomas (PAs) present similar imaging features on conventional MR imaging, making differential diagnosis a challenge. The purpose of this study was to evaluate the usefulness of dynamic susceptibility-weighted contrast-enhanced perfusion-weighted imaging (DSC-PWI) and proton MR spectroscopic imaging in the differentiation of hemangioblastomas and PAs. METHODS: A 3.0-T MR imaging unit was used to perform DSC-PWI and conventional MR imaging on 14 patients with hemangioblastomas and 22 patients with PAs. Four patients with hemangioblastomas and 10 PA patients also underwent proton MR spectroscopy. Parameters of relative peak height (rPH) and relative percentage of signal intensity recovery (rPSR) were acquired by DSC-PWI and variables of N-acetylaspasrtate (NAA)/creatine (Cr), choline (Cho)/Cr, and lactate-lipid (Lac-Lip)/Cr by MR spectroscopy. The sensitivity, specificity, and the area under the receiver operating characteristic curve of all analyzed parameters at respective cutoff values were determined. RESULTS: Higher rPH but lower rPSR values were detected in hemangioblastomas compared to PAs. The NAA/Cr ratio was significantly lower in hemangioblastomas compared with PAs. The threshold values ≥3.2 for rPH provide sensitivity, specificity, positive predictive values, and negative predictive values of 85.7, 95.5, 92.3, and 91.3%, respectively, for differentiating hemangioblastomas from PAs. The optimal threshold values were ≤0.9 for rPSR and ≤1.5 for NAA/Cr ratios in tumor. CONCLUSION: Significantly higher rPH and lower NAA/Cr were seen in patients with hemangioblastomas when compared with PA patients, suggesting that DSC-PWI and proton MR spectroscopy are helpful in the characterization and differentiation of these two types of tumors.


Assuntos
Astrocitoma/diagnóstico , Biomarcadores Tumorais/análise , Neoplasias Encefálicas/diagnóstico , Hemangioblastoma/diagnóstico , Angiografia por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética/métodos , Adolescente , Adulto , Idoso , Astrocitoma/química , Neoplasias Encefálicas/química , Criança , Pré-Escolar , Diagnóstico por Computador/métodos , Diagnóstico Diferencial , Feminino , Hemangioblastoma/química , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto Jovem
13.
Folia Med (Plovdiv) ; 56(3): 194-8, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25434077

RESUMO

INTRODUCTION: YKL-40 is a glycoprotein believed potentially to be a marker of various pathological processes. High levels of YKL-40 have been found in cancer and chronic inflammatory diseases. The function of the glycoprotein is not completely known yet. A possible involvement in angiogenesis and tumor aggressiveness is supposed. Lysosome-associated membrane glycoproteins (LAMP) 1 and 2 are highly conserved proteins with still undefined biological functions. There is evidence that they are implicated in autophagy, angiogenesis and tissue remodeling. AIM: The aim of the present study was to investigate the potential relationship between the tissue expression of YKL-40, LAMP-1 and LAMP-2 in glial tumors. MATERIAL AND METHODS: LAMPs and YKL-40 expression was determined by immunohistochemistry in 36 glial tumors. A morphometric analysis of the intensity of tissue expression was performed with the Quick-photo Micro 2.3. system. Area (µm), perimeter (µm), and expression level (%) of the three glycoproteins were calculated. RESULTS: LAMPs were found on cell membranes of glial and endothelial cells, while YKL-40 was detected in the cytoplasm of these cells. Intensive immunohistochemical reaction was present in tumor cells. LAMP-2 showed a more intensive staining compared to LAMP-1. CONCLUSION: We present the first comparative study of YKL-40 and LAMPs in astroglial tumors. The relationship between the expression of the three glycoconjugates indicates a possible participation in the processes of angiogenesis and tissue remodeling during tumor development.


Assuntos
Adipocinas/análise , Astrocitoma/química , Glioblastoma/química , Lectinas/análise , Proteína 2 de Membrana Associada ao Lisossomo/análise , Glicoproteínas de Membrana Associadas ao Lisossomo/análise , Idoso , Proteína 1 Semelhante à Quitinase-3 , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade
14.
Oncotarget ; 5(18): 8083-92, 2014 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-25257301

RESUMO

Classifying adult gliomas remains largely a histologic diagnosis based on morphology; however astrocytic, oligodendroglial and mixed lineage tumors can display overlapping histologic features. We used multiplexed exome sequencing (OncoPanel) on 108 primary or recurrent adult gliomas, comprising 65 oligodendrogliomas, 28 astrocytomas and 15 mixed oligoastrocytomas to identify lesions that could enhance lineage classification. Mutations in TP53 (20/28, 71%) and ATRX (15/28, 54%) were enriched in astrocytic tumors compared to oligodendroglial tumors of which 4/65 (6%) had mutations in TP53 and 2/65 (3%) had ATRX mutations. We found that oligoastrocytomas harbored mutations in TP53 (80%, 12/15) and ATRX (60%, 9/15) at frequencies similar to pure astrocytic tumors, suggesting that oligoastrocytomas and astrocytomas may represent a single genetic or biological entity. p53 protein expression correlated with mutation status and showed significant increases in astrocytomas and oligoastrocytomas compared to oligodendrogliomas, a finding that also may facilitate accurate classification. Furthermore our OncoPanel analysis revealed that 15% of IDH1/2 mutant gliomas would not be detected by traditional IDH1 (p.R132H) antibody testing, supporting the use of genomic technologies in providing clinically relevant data. In all, our results demonstrate that multiplexed exome sequencing can support evaluation and classification of adult low-grade gliomas with a single clinical test.


Assuntos
Astrocitoma/genética , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/genética , Linhagem da Célula , Análise Mutacional de DNA , Exoma , Testes Genéticos/métodos , Mutação , Oligodendroglioma/genética , Astrocitoma/química , Astrocitoma/classificação , Astrocitoma/patologia , Biomarcadores Tumorais/análise , Neoplasias Encefálicas/química , Neoplasias Encefálicas/classificação , Neoplasias Encefálicas/patologia , DNA Helicases/genética , Diagnóstico Diferencial , Receptores ErbB/genética , Perfilação da Expressão Gênica , Predisposição Genética para Doença , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imuno-Histoquímica , Isocitrato Desidrogenase/genética , Proteínas Nucleares/genética , Oligodendroglioma/química , Oligodendroglioma/classificação , Oligodendroglioma/patologia , PTEN Fosfo-Hidrolase/genética , Fenótipo , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Proteína Supressora de Tumor p53/genética , Proteína Nuclear Ligada ao X
15.
J Clin Pathol ; 67(7): 556-61, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24607494

RESUMO

AIMS: The zinc finger transcription factor WT1 is expressed in astrocytic neoplasms and therefore is a potential target of immunotherapy in brain tumours. Our aim was to further elucidate the role of WT1 as a diagnostic and prognostic marker in neuropathology, particularly as to the differentiation of astrocytoma from oligodendroglioma as well as to the dependency of WT1 expression on clinically relevant parameters. METHODS: 829 evaluable brain tumour samples were investigated by WT1 immunohistochemistry on full tissue routine slides, consisting of 442 glioblastomas, 303 astrocytomas, 41 oligodendrogliomas and 43 oligoastrocytomas. In addition public WT1 gene expression data of 351 gliomas were analysed. RESULTS: Our data show that WT1 expression in diffuse astrocytic tumours increases with WHO tumour grade and is associated with older age, absence of IDH1 mutation but not related to O(6)- methyl guanine methyl transferase (MGMT) promoter methylation status. Univariable, but not multivariable survival analysis indicates that WT1 expression is associated with worse outcome in patients with diffuse astrocytoma but not glioblastoma. CONCLUSIONS: The significant WT1 expression differences between diffuse astrocytomas, oligoastrocytomas and oligodendrogliomas, which are also present in the Repository for Molecular Brain Neoplasia Data, National Cancer Institute (REMBRANDT, 2005, http://rembrandt.nci.nih.gov) gene database set, provide a rationale for use of WT1 as part of a routine immunohistochemistry panel.


Assuntos
Astrocitoma/química , Biomarcadores Tumorais/análise , Neoplasias Encefálicas/química , Oligodendroglioma/química , Proteínas WT1/análise , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Astrocitoma/genética , Astrocitoma/mortalidade , Astrocitoma/patologia , Astrocitoma/terapia , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/terapia , Criança , Pré-Escolar , Metilação de DNA , Metilases de Modificação do DNA/genética , Análise Mutacional de DNA , Enzimas Reparadoras do DNA/genética , Bases de Dados Genéticas , Feminino , Genes do Tumor de Wilms , Predisposição Genética para Doença , Humanos , Imuno-Histoquímica , Lactente , Isocitrato Desidrogenase/genética , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mutação , Gradação de Tumores , Oligodendroglioma/genética , Oligodendroglioma/mortalidade , Oligodendroglioma/patologia , Oligodendroglioma/terapia , Fenótipo , Reação em Cadeia da Polimerase , Valor Preditivo dos Testes , Prognóstico , Regiões Promotoras Genéticas , Fatores de Risco , Análise Serial de Tecidos , Proteínas Supressoras de Tumor/genética , Regulação para Cima , Proteínas WT1/genética , Adulto Jovem
16.
Int J Cancer ; 134(5): 1123-31, 2014 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-24037901

RESUMO

Recent studies suggest that the regulatory networks controlling the functions of stem cells during development may be abnormally active in human cancers. An embryonic stem cell (ESC) gene signature was found to correlate with a more undifferentiated phenotype of several human cancer types including gliomas, and associated with poor prognosis in breast cancer. In the present study, we used tissue microarrays of 80 low-grade (WHO Grade II) and 98 high-grade human gliomas (WHO Grades III and IV) to investigate the presence of the ESC-related proteins Nanog, Klf4, Oct4, Sox2 and c-Myc by immunohistochemistry. While similar patterns of co-expressed proteins between low- and high-grade gliomas were present, we found up-regulated protein levels of Nanog, Klf4, Oct4 and Sox2 in high-grade gliomas. Survival analysis by Kaplan-Meier analysis revealed a significant shorter survival in the subgroups of low-grade astrocytomas (n = 42) with high levels of Nanog protein (p = 0.0067) and of Klf4 protein (p = 0.0368), in high-grade astrocytomas (n = 85) with high levels of Nanog (p = 0.0042), Klf4 (p = 0.0447), and c-Myc (p = 0.0078) and in glioblastomas only (n = 71) with high levels of Nanog (p = 0.0422) and of c-Myc (p = 0.0256). In the multivariate model, Nanog was identified as an independent prognostic factor in the subgroups of low-grade astrocytomas (p = 0.0039), high-grade astrocytomas (p = 0.0124) and glioblastomas only (p = 0.0544), together with established clinical variables in these tumors. These findings provide further evidence for the joint regulatory pathways of ESC-related proteins in gliomas and identify Nanog as one of the key players in determining clinical outcome of human astrocytomas.


Assuntos
Astrocitoma/química , Neoplasias Encefálicas/química , Células-Tronco Embrionárias/química , Proteínas de Homeodomínio/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Astrocitoma/mortalidade , Neoplasias Encefálicas/mortalidade , Feminino , Humanos , Imuno-Histoquímica , Isocitrato Desidrogenase/genética , Fatores de Transcrição Kruppel-Like/análise , Masculino , Pessoa de Meia-Idade , Proteína Homeobox Nanog , Proteínas Proto-Oncogênicas c-myc/análise , Análise Serial de Tecidos
17.
J BUON ; 18(4): 1006-11, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24344030

RESUMO

PURPOSE: To investigate the expression of CDC25B, which is a member of the cyclin-dependent kinase activating phosphatase family, in diffuse astrocytoma (DA), anaplastic astrocytoma (AA), glioblastoma multiforme (GBM), pilocytic astrocytoma (PA) and reactive gliosis (RG). Also, to study the relationship of the expression level of CDC25B with clinical parameters and with p53 and Ki-67 proliferation index (PI). METHODS: Tissues were collected from 36 cases diagnosed with astrocytoma (10 DA, 6 AA, 20 GBM), 10 PA, 10 RG and 10 normal brain tissues for controlling purposes. The sections were immunohistochemically stained with CDC25B, Ki-67 and p53. For each marker, 1000 tumor cells were counted and the ratio of positive tumor cells was calculated. RESULTS: The average CDC2B staining index (CSI) was 0.6% in PA, 0.4% in DA , 7.7% in AA and 25.5% in GBM. The increase of CSI in parallel with the increase of WHO grade was significant (p=0.001). No expressions were identified in RG and normal brain. There was also significant relationship between the tumor size and CSI (p=0.027) and also between Ki-67 PI and CSI (p=0.001). Among the groups with low and high CSI in astrocytoma cases, the disease free survival (DFS) was significantly higher in the low CSI group (p=0.0001). CONCLUSIONS: Positive expression of CDC25B in astrocytoma affects the prognosis in an adverse manner. CSI can be used as a diagnostic method and CDC25B may be a possible target molecule for treatment.


Assuntos
Astrocitoma/química , Neoplasias Encefálicas/química , Encéfalo/metabolismo , Gliose , Antígeno Ki-67/análise , Proteína Supressora de Tumor p53/análise , Fosfatases cdc25/análise , Adolescente , Adulto , Astrocitoma/patologia , Astrocitoma/terapia , Encéfalo/patologia , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/terapia , Proliferação de Células , Distribuição de Qui-Quadrado , Intervalo Livre de Doença , Feminino , Glioblastoma/química , Glioblastoma/patologia , Glioblastoma/terapia , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Gradação de Tumores , Modelos de Riscos Proporcionais , Fatores de Risco , Carga Tumoral
18.
Anal Bioanal Chem ; 405(27): 8719-28, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23934397

RESUMO

Hyperspectral unmixing is an unsupervised algorithm to calculate a bilinear model of spectral endmembers and abundances of components from Raman images. Thirty-nine Raman images were collected from six glioma brain tumor specimens. The tumor grades ranged from astrocytoma WHO II to glioblastoma multiforme WHO IV. The abundance plots of the cell nuclei were processed by an image segmentation procedure to determine the average nuclei size, the number of nuclei, and the fraction of nuclei area. The latter two morphological parameters correlated with the malignancy. A combination of spectral unmixing and non-negativity constrained linear least squares fitting is introduced to assess chemical parameters. First, endmembers of the most abundant and most dissimilar components were defined that represent all data sets. Second, the content of the obtained components' proteins, nucleic acids, lipids, and lipid to protein ratios were determined in all Raman images. Except for the protein content, all chemical parameters correlated with the malignancy. We conclude that the morphological and chemical information offer new ways to develop Raman-based classification approaches that can complement diagnosis of brain tumors. The role of non-linear Raman modalities to speed-up image acquisition is discussed.


Assuntos
Algoritmos , Astrocitoma/diagnóstico , Biomarcadores Tumorais/análise , Neoplasias Encefálicas/diagnóstico , Glioblastoma/diagnóstico , Análise Espectral Raman , Astrocitoma/química , Astrocitoma/patologia , Neoplasias Encefálicas/química , Neoplasias Encefálicas/patologia , Núcleo Celular/ultraestrutura , Glioblastoma/química , Glioblastoma/patologia , Humanos , Processamento de Imagem Assistida por Computador , Análise dos Mínimos Quadrados , Lipídeos/análise , Gradação de Tumores , Proteínas de Neoplasias/análise , Ácidos Nucleicos/análise , Tamanho das Organelas
19.
Anal Bioanal Chem ; 405(23): 7321-35, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23877172

RESUMO

In this preliminary investigation, a low-grade astrocytoma (AcT) is investigated by high-resolution (HR) mass spectrometry (MS) aiming at characterization of gangliosides with potential biomarker value. The research was conducted towards a comparative mapping of ganglioside expression in AcT, its surrounding tissue (ST) and a normal control brain tissue (NT). HR MS was conducted in the negative ion mode nanoelectrospray ionization (nanoESI). Fragmentation analysis was carried out by collision-induced dissociation (CID) MS(2)-MS(4.) Due to the high resolving power and mass accuracy, by comparative mapping of the ganglioside extracts from AcT, ST and NT, under identical conditions, 37 different species in AcT, 40 in ST and 56 in NT were identified. AcT and ST were found to contain 18 identical ganglioside components. Among all three specimens, ST extract presented the highest levels of sialylation, fucosylation and acetylation, a feature which might be correlated to the tumor expansion in the adjacent brain area. MS mapping indicated also that AcT, ST and NT share one doubly deprotonated molecule at m/z 1063.31, attributable to GT1(d18:1/18:0) or GT1(d18:0/18:1). CID MS(2)-MS(4) on these particular ions detected in AcT and ST provided data supporting GT1c isomer in the investigated astrocytoma tissue. Our results show that HR MS has a remarkable potential in brain cancer research for the determination of tumor-associated markers and for their structural determination.


Assuntos
Astrocitoma/química , Neoplasias Encefálicas/química , Gangliosídeos/análise , Acetilação , Adulto , Astrocitoma/diagnóstico , Biomarcadores/análise , Biomarcadores/química , Química Encefálica , Neoplasias Encefálicas/diagnóstico , Sequência de Carboidratos , Fucose/análise , Fucose/química , Gangliosídeos/química , Humanos , Masculino , Dados de Sequência Molecular , Ácido N-Acetilneuramínico/análise , Ácido N-Acetilneuramínico/química , Gradação de Tumores , Espectrometria de Massas por Ionização por Electrospray/métodos , Microambiente Tumoral
20.
ACS Chem Neurosci ; 4(10): 1371-81, 2013 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-23875773

RESUMO

Neurokinin B (NKB) is a member of the tachykinin family of neuropeptides that have neuroinflammatory, neuroimmunological, and neuroprotective functions. In a neuroprotective role, tachykinins can help protect cells against the neurotoxic processes observed in Alzheimer's disease. A change in copper homeostasis is a clear feature of Alzheimer's disease, and the dysregulation may be a contributory factor in toxicity. Copper has recently been shown to interact with neurokinin A and neuropeptide γ and can lead to generation of reactive oxygen species and peptide degradation, which suggests that copper may have a place in tachykinin function and potentially misfunction. To explore this, we have utilized a range of spectroscopic techniques to show that NKB, but not substance P, can bind Cu(II) in an unusual [Cu(II)(NKB)2] neutral complex that utilizes two N-terminal amine and two imidazole nitrogen ligands (from each molecule of NKB) and the binding substantially alters the structure of the peptide. Using 1321N1 astrocytoma cells, we show that copper can enter the cells and subsequently open plasma membrane calcium channels but when bound to neurokinin B copper ion uptake is inhibited. This data suggests a novel role for neurokinin B in protecting cells against copper-induced calcium changes and implicates the peptide in synaptic copper homeostasis.


Assuntos
Doença de Alzheimer/metabolismo , Astrocitoma/química , Astrocitoma/metabolismo , Cobre/química , Neurocinina B/química , Doença de Alzheimer/patologia , Doença de Alzheimer/prevenção & controle , Astrocitoma/patologia , Linhagem Celular Tumoral , Complexos de Coordenação/química , Complexos de Coordenação/metabolismo , Cobre/metabolismo , Humanos , Neurocinina B/antagonistas & inibidores , Neurocinina B/metabolismo , Peptídeos/química , Peptídeos/metabolismo , Ligação Proteica
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