Avaliação bioquímica da isquemia cerebral focal, não associada à reperfusão, por oclusão da artéria cerebral média em ratos

Cerebral ischemia is an important event in clinical and surgical neurological practice since it is one of the diseases that most compromise the human species. In the present study 40 adult rats were submitted to periods of focal ischemia of 30, 60 and 90 min without reperfusion and animals submitted to a sham procedure were used as controls. We analyzed the levels of ATP, malondialdehyde and caspase-3. No significant differences in the biochemical measurements were observed between the right and left brain hemispheres of the same animal in each experimental group. Reduced ATP levels were observed after the three periods of ischemia compared to the sham group. No significant increase in malondialdehyde or caspase-3 levels was observed. Despite significant changes in ATP levels, the results indicated cell viability in the ischemic region as shown by the low rates of lipid peroxidation and apoptosis, findings probably related to the lack of reperfusion.Isquemia cerebral é um acontecimento importante na prática neurológica clínica e cirúrgica, uma vez que é uma das doenças que mais comprometem a espécie humana. No presente estudo 40 ratos adultos foram submetidos a períodos de isquemia focal de 30, 60 e 90 min e como controle foram utilizados animais do grupo sham. Foram analisados os níveis de ATP, malondialdeído e caspase-3. Nenhuma diferença significativa nas dosagens bioquímicas foram observadas entre os hemisférios cerebrais direito e esquerdo do mesmo animal em cada grupo experimental. Foi observada redução nos níveis de ATP após os três períodos de isquemia, em comparação com o grupo sham. Nenhum aumento significativo dos níveis de malondialdeído ou caspase-3 foi observado. Apesar das alterações significativas nos níveis ATP, os resultados indicaram viabilidade celular na região isquêmica como demonstrado pela baixa taxa de peroxidação lipídica e apoptose, achados que provavelmente estão relacionados com a falta de reperfusão

Níveis diferentes de MT-I/II entre pacientes com MTLE com ou sem crise generalizada: os níveis hipocampais de MT-I/II afetam o alastramento das crises, ou o alastramento das crises promove expressão diferencial de MT-I/II?

In the central nervous system, zinc is released along with glutamate during neurotransmission and, in excess, can promote neuronal death. Experimental studies have shown that metallothioneins I/II (MT-I/II), which chelate free zinc, can affect seizures and reduce neuronal death after status epilepticus. Our aim was to evaluate the expression of MT-I/II in the hippocampus of patients with temporal lobe epilepsy (TLE). Hippocampi from patients with pharmacoresistant mesial temporal lobe epilepsy (MTLE) were evaluated for expression of MT-I/II and for neuronal, astroglial, and microglial populations. Compared to control cases, MTLE group displayed widespread increase in MT-I/II expression, astrogliosis and reduced neuronal population. MT-I/II levels did not correlate with any clinical variables, but patients with secondary generalized seizures (SGS) had less MT-I/II than patients without SGS. In conclusion, MT-I/II expression was increased in hippocampi from MTLE patients and our data suggest that it may be associated with different seizure spread patterns

Alterations in gene expression profiles correlated with cisplatin cytotoxicity in the glioma U343 cell line

Gliomas are the most common tumors in the central nervous system, the average survival time of patients with glioblastoma multiforme being about 1 year from diagnosis, in spite of harsh therapy. Aiming to study the transcriptional profiles displayed by glioma cells undergoing cisplatin treatment, gene expression analysis was performed by the cDNA microarray method. Cell survival and apoptosis induction following treatment were also evaluated. Drug concentrations of 12.5 to 300 μM caused a pronounced reduction in cell survival rates five days after treatment, whereas concentrations higher than 25 μM were effective in reducing the survival rates to ~1%. However, the maximum apoptosis frequency was 20.4% for 25 μM cisplatin in cells analyzed at 72 h, indicating that apoptosis is not the only kind of cell death induced by cisplatin. An analysis of gene expression revealed 67 significantly (FDR < 0.05) modulated genes: 29 of which down- and 38 up-regulated. These genes belong to several classes (metabolism, protein localization, cell proliferation, apoptosis, adhesion, stress response, cell cycle and DNA repair) that may represent several affected cell processes under the influence of cisplatin treatment. The expression pattern of three genes (RHOA, LIMK2 and TIMP2) was confirmed by the real time PCR method

Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma

Therapy development for adult diffuse glioma is hindered by incomplete knowledge of somatic glioma driving alterations and suboptimal disease classification. We defined the complete set of genes associated with 1,122 diffuse grade II-III-IV gliomas from The Cancer Genome Atlas and used molecular profiles to improve disease classification, identify molecular correlations, and provide insights into the progression from low- to high-grade disease. Whole-genome sequencing data analysis determined that ATRX but not TERT promoter mutations are associated with increased telomere length. Recent advances in glioma classification based on IDH mutation and 1p/19q co-deletion status were recapitulated through analysis of DNA methylation profiles, which identified clinically relevant molecular subsets. A subtype of IDH mutant glioma was associated with DNA demethylation and poor outcome; a group of IDH-wild-type diffuse glioma showed molecular similarity to pilocytic astrocytoma and relatively favorable survival. Understanding of cohesive disease groups may aid improved clinical outcomes

Molecular characterization and clinical relevance of metabolic expression subtypes in human cancers.

Metabolic reprogramming provides critical information for clinical oncology. Using molecular data of 9,125 patient samples from The Cancer Genome Atlas, we identified tumor subtypes in 33 cancer types based on mRNA expression patterns of seven major metabolic processes and assessed their clinical relevance. Our metabolic expression subtypes correlated extensively with clinical outcome: subtypes with upregulated carbohydrate, nucleotide, and vitamin/cofactor metabolism most consistently correlated with worse prognosis, whereas subtypes with upregulated lipid metabolism showed the opposite. Metabolic subtypes correlated with diverse somatic drivers but exhibited effects convergent on cancer hallmark pathways and were modulated by highly recurrent master regulators across cancer types. As a proof-of-concept example, we demonstrated that knockdown of SNAI1 or RUNX1—master regulators of carbohydrate metabolic subtypes-modulates metabolic activity and drug sensitivity. Our study provides a system-level view of metabolic heterogeneity within and across cancer types and identifies pathway cross-talk, suggesting related prognostic, therapeutic, and predictive utility

Qualidade de vida e sintomas de ansiedade e depressão em pacientes com tumores cerebrais primários

Objetivo: Avaliar a qualidade de vida e sintomas de ansiedade e depress&#227;o em pacientes com diagn&#243;stico de meningioma e glioma de alto grau submetidos &#224; neurocirurgia oncol&#243;gica. M&#233;todos: Para a coleta de dados, foram aplicados dois instrumentos validados no Brasil: Hospital Anxiety and Depression Scale (HAD) e Item Short-Form Health Survey (SF-36). Resultados: Foram identificadas diferen&#231;as estatisticamente significativas quando comparados os dados do SF-36 de ambos os grupos tumorais, no pr&#233; e p&#243;s-operat&#243;rio, nos aspectos: capacidade funcional (p = 0,043), aspecto emocional (p = 0,042) e sa&#250;de mental (p = 0,042) referente ao grupo meningioma. Quando comparados com respectivos grupos controle, houve diferen&#231;as significativas entre os grupos meningioma e controle, nos aspectos f&#237;sico (p = 0,002) e emocional (p = 0,004), e entre os grupos glioma de alto grau e controle, nos aspectos capacidade funcional (p = 0,003) e f&#237;sico (p = 0,003). Conclus&#227;o: A cirurgia oncol&#243;gica gerou altera&#231;&#245;es de humor e na qualidade de vida em ambos os grupos, independente do tipo histol&#243;gico do tumor. Apesar da relev&#226;ncia do tema, ainda s&#227;o poucos os estudos sobre o tema