ASPM gene expression in medulloblastoma.

PURPOSE: Medulloblastomas are the most common malignant tumors of the central nervous system in childhood. The incidence is about 19-20% between children younger than 16 years old with peak incidence between 4 and 7 years. Despite its sensibility to no specific therapeutic means like chemotherapy and radiotherapy, the treatment is very aggressive and frequently results in regression, growth deficit, and endocrine dysfunction. From this point of view, new treatment approaches are needed such as molecular targeted therapies. Studies in glioblastoma demonstrated that ASPM gene was overexpressed when compared to normal brain and ASPM inhibition by siRNA-mediated inhibits tumor cell proliferation and neural stem cell proliferation, supporting ASPM gene as a potential molecular target in glioblastoma. The aim of this work was to evaluate ASPM expression in medulloblastoma fragment samples, and to compare the results with the patient clinical features. METHODS: Analysis of gene expression was performed by quantitative PCR real time using SYBR Green system in tumor samples from 37 children. The t test was used to analyze the gene expression, and Mann-Whitney test was performed to analyze the relationship between gene expressions and clinical characteristics. Kaplan-Meier test evaluated curve survival. RESULTS: All samples overexpressed ASPM gene more than 40-fold. However, we did not find any association between the overexpressed samples and the clinical parameters. CONCLUSION: ASPM overexpression may modify the ability of stem cells to differentiate during the development of the central nervous system, contributing to the development of medulloblastoma, a tumor of embryonic origin from cerebellar progenitor cells.

Experimental nodel of C6 brain tumors in athymic rats.

Malignant brain tumor experimental models tend to employ cells that are immunologically compatible with the receptor animal. In this study, we have proposed an experimental model of encephalic tumor development by injecting C6 cells into athymic Rowett rats, aiming at reaching a model which more closely resembles to the human glioma tumor. In our model, we observed micro-infiltration of tumor cell clusters in the vicinity of the main tumor mass, and of more distal isolated tumor cells immersed in normal encephalic parenchyma. This degree of infiltration is superior to that usually observed in other C6 models.

Intracranial meningiomas: magnetic resonance imaging findings in 78 cases.

OBJECTIVE: To present the magnetic resonance (MR) imaging findings of 78 patients with meningiomas diagnosed in a single institution. METHOD: 78 patients with histological proven intracranial meningioma were studied. There were 52 female and 26 male patients (median=56 years). All MR imaging examinations were performed with 1.5-T MR imaging unit with standard protocol. The images were studied by two neuroradiologists, who reached the decisions regarding the findings by consensus. RESULTS: Most of the tumors showed low signal on T1- (60%) and high signal on T2- (68%) and FLAIR (69%) weighted images. Also, the lesions showed heterogeneous signal on T1 (60%), T2 (68%) and FLAIR (64%) sequences. After contrast administration, 83% (n=65) of the tumors presented accentuated and 17% (n=13) showed moderate enhancement. The tumors were located in the frontal lobe in 44% of the cases, in the parietal lobe in 35%, the occipital lobe in 19% and the temporal lobe in 12% of the patients. Areas of vasogenic edema around the tumors were seen in 90% of the cases. Twenty six per cent of the cases showed bone infiltration, and the dural tail sign was seen in 59% of the tumors. CONCLUSION: Intracranial meningiomas usually show heterogeneous low signal on T1- and high signal on T2-weighted and FLAIR images, with intense enhancement after contrast administration. The frontal and parietal lobes are commonly affected. In addition, brain edema, dural tail sign and bone infiltration are the most frequent associated findings.

Leukocyte mitochondrial DNA copy number in bipolar disorder.

BACKGROUND: Evidence supports the role for mitochondrial impairment in the pathophysiology of bipolar disorder (BD). BD has been associated with decreased mitochondrial electron transport chain activity and increased oxidative stress. Also, mitochondrial DNA (mtDNA) encodes mitochondrial electron transport chain proteins and has been associated with altered oxidative stress. Preclinical studies showed that lithium treatment increased mtDNA content, but no study has directly assessed mtDNA content in subjects with BD in vivo. Also, the effects of lithium treatment on mtDNA content have never been evaluated in humans. METHODS: Leukocyte mtDNA content using real time-PCR was evaluated in subjects with BD (n=23) in a depressive episode (≥18 in the 21-item Hamilton Depression Rating Scale) before and after 6-week lithium treatment versus healthy controls (n=24). RESULTS: mtDNA content showed no significant difference between subjects with BD at baseline and controls (p=0.46); also no difference was observed when comparing before and after lithium treatment. A trend for decreased mtDNA content was specifically observed in BD type I compared to controls and BD type II (p=0.05). Importantly, endpoint mtDNA copy number was significantly correlated with age. CONCLUSION: In BD subjects who were younger, unmedicated and had a shorter duration of illness, no change was observed in mtDNA copy number. More studies with larger samples are warranted to evaluate mtDNA content changes in BD and its potential role as a treatment target, especially in BD type I and its association with aging.

Effects of high adherence to mediterranean or low-fat diets in medicated secondary prevention patients.

Although the Mediterranean diet (MD) and the low-fat Therapeutic Lifestyle Changes Diet (TLCD) promote equivalent increases in event-free survival in secondary coronary prevention, possible mechanisms of such complete dietary patterns in these patients, usually medicated, are unclear. The aim of this study was to investigate the effects of the MD versus the TLCD in markers of endothelial function, oxidative stress, and inflammation after acute coronary syndromes. Comparison was made between 3 months of the MD (n = 21; rich in whole grains, vegetables, fruits, nuts, and olive oil, plus red wine) and the TLCD (n = 19; plus phytosterols 2 g/day) in a highly homogenous population of stable patients who experienced coronary events in the previous 2 years (aged 45 to 65 years, all men) allocated to each diet under a strategy designed to optimize adherence, documented as >90%. Baseline demographics, body mass index and clinical data, and use of statins and other drugs were similar between groups. The MD and TLCD promoted similar decreases in body mass index and blood pressure (p ≤0.001) and particularly in plasma asymmetric dimethylarginine levels (p = 0.02) and l-arginine/asymmetric dimethylarginine ratios (p = 0.01). The 2 diets did not further enhance flow-mediated brachial artery dilation compared to baseline (4.4 ± 4.0%). Compared to the TLCD, the MD promoted decreases in blood leukocyte count (p = 0.025) and increases in high-density lipoprotein levels (p = 0.053) and baseline brachial artery diameter. Compared to the MD, the TLCD decreased low-density lipoprotein and oxidized low-density lipoprotein plasma levels, although the ratio of oxidized to total low-density lipoprotein remained unaltered. Glucose, high-sensitivity C-reactive protein, triglycerides, myeloperoxidase, intercellular adhesion molecular, vascular cell adhesion molecule, and glutathione serum and plasma levels remained unchanged with either diet. In conclusion, medicated secondary prevention patients show evident although small responses to the MD and the TLCD, with improved markers of redox homeostasis and metabolic effects potentially related to atheroprotection.

Pleiotrophin expression in astrocytic and oligodendroglial tumors and it's correlation with histological diagnosis, microvascular density, cellular proliferation and overall survival.

BACKGROUND: Pleiotrophin (PTN) is a secreted cytokine with several properties related with tumor development, including differentiation, angiogenesis, invasion, apoptosis and metastasis. There is evidence that PTN has also a relevant role in primary brain neoplasms and its inactivation could be important to treatment response. Astrocytic and oligodendroglial tumors are the most frequent primary brain neoplasms. Astrocytic tumors are classified as pilocytic astrocytoma (PA), diffuse astrocytoma (DA), anaplastic astrocytoma (AA) and glioblastoma (GBM). Oligodendroglial tumors are classified as oligodendroglioma (O) and anaplastic oligodendroglioma (AO). The aim of the present study was to compare PTN expression, in astrocytomas and oligodendrogliomas and its association with the histological diagnosis, microvascular density, proliferate potential and clinical outcome. METHODS: Seventy-eight central nervous system tumors were analyzed. The histological diagnosis in accordance with WHO classification was: 13PA, 18DA, 8AA, 15GBM, 16O and 8AO. Immunohistochemistry was realized with these specific antibodies: pleiotrophin, CD31 to microvascular density and Ki-67 to cell proliferation. RESULTS: PTN expression was significantly higher in GBM and AA when compared to PA and higher in GBM compared to DA. PTN expression did not differ between O and AO. Proliferate index and microvascular density were evaluated only in high grade tumors (AA, GBM and AO) divided in three groups according to PTN expression (low, intermediate and high). These results showed no statistical difference between PTN expression and index of cellular proliferation and neither to PTN expression and microvascular density. Overall survival (OS) analysis (months) showed similar results in high grade gliomas with different levels of PTN expression. CONCLUSIONS: Our results suggest that PTN expression is associated with histopathological grade of astrocytomas. Proliferation rate, microvascular density and overall survival do not seem to be associated with PTN expression.

Experimental nodel of C6 brain tumors in athymic rats / Modelo experimental de tumor cerebral C6 em ratos atímicos

Malignant brain tumor experimental models tend to employ cells that are immunologically compatible with the receptor animal. In this study, we have proposed an experimental model of encephalic tumor development by injecting C6 cells into athymic Rowett rats, aiming at reaching a model which more closely resembles to the human glioma tumor. In our model, we observed micro-infiltration of tumor cell clusters in the vicinity of the main tumor mass, and of more distal isolated tumor cells immersed in normal encephalic parenchyma. This degree of infiltration is superior to that usually observed in other C6 models.

Modelos experimentais de tumores cerebrais malignos geralmente utilizam células imunologicamente compatíveis com o animal receptor. Neste estudo apresentamos um modelo experimental baseado na inoculação de células C6 em ratos atímicos Rowett, visando obter um tumor que se assemelhe mais àqueles observados nos seres humanos. Neste modelo observamos microinfiltração de ilhotas de células na periferia da massa tumoral principal e nas áreas mais distantes, células tumorais isoladas no tecido cerebral normal. Este grau de infiltração é superior àquele observado em outros modelos utilizando as células C6.

Intracranial meningiomas: magnetic resonance imaging findings in 78 cases

OBJECTIVE: To present the magnetic resonance (MR) imaging findings of 78 patients with meningiomas diagnosed in a single institution. METHOD: 78 patients with histological proven intracranial meningioma were studied. There were 52 female and 26 male patients (median=56 years). All MR imaging examinations were performed with 1.5-T MR imaging unit with standard protocol. The images were studied by two neuroradiologists, who reached the decisions regarding the findings by consensus. RESULTS: Most of the tumors showed low signal on T1- (60 percent) and high signl on T2- (68 percent) and FLAIR (69 percent) weighted images. Also, the lesions showed heterogeneous signal on T1 (60 percent), T2 (68 percent) and FLAIR (64 percent) sequences. After contrast administration, 83 percent (n=65) of the tumors presented acentuated and 17 percent (n=13) showed moderate enhancement. The tumors were located in the frontal lobe in 44 percent of the cases, in the parietal lobe in 35 percent, the occipital lobe in 19 percent and the temporal lobe in 12 percent of the patients. Areas of vasogenic edema around the tumors were seen in 90 percent of the cases. Twenty six per cent of the cases showed bone infiltration, and the dural tail sign was seen in 59 percent of the tumors. CONCLUSION: Intracranial meningiomas usually show heterogeneous low signal on T1- and high signal on T2-weighted and FLAIR images, with intense enhancement after contrast administration. The frontal and parietal lobes are commonly affected. In addition, brain edema, dural tail sign and bone infiltration are the most frequent associated findings.

OBJETIVO: Apresentar os achados de ressonância magnética (RM) de 78 pacientes com meningioma intracraniano diagnosticados numa única instituição. MÉTODO: 78 pacientes com diagnóstico histológico de meningioma intracraniano foram estudados. Cinqüenta e dois eram femininos e 26 masculinos (mediana=56 anos). Todos os exames de RM foram realizados num aparelho de 1.5 Tesla, com protocolo padrão. As imagens foram avaliadas por dois neurorradiologistas, os quais estabeleceram os achados por consenso. RESULTADOS: A maioria dos tumores apresentou baixo sinal em T1 (60 por cento) e alto sinal em T2 (68 por cento) e FLAIR (69 por cento). Além disso, as lesões demonstraram sinal heterogêneo em T1 (60 por cento), T2 (68 por cento) e FLAIR (64 por cento). Após a administração intravenosa de contraste, 83 por cento dos tumores apresentaram realce acentuado e 17 por cento moderado. Os tumores estavam localizados no lobo frontal em 44 por cento dos casos, no parietal em 35 por cento, no occipital em 19 por cento e no lobo temporal em 12 por cento dos casos. Areas de edema vasogênico foram observadas em 90 por cento dos pacientes. Vinte e seis por cento dos casos apresentaram sinais de infiltração óssea e o sinal da cauda dural foi visto em 59 por cento dos tumores. CONCLUSÃO: Meningiomas intracranianos em geral apresentam sinal heterogêneo, baixo em T1 e alto em T2 e FLAIR, com intenso realce pelo contraste. Os lobos frontais e parietais são com freqüência acometidos. Além disso, edema vasogênico, sinal da cauda dural e infiltração óssea são os achados associados mais comuns.