RESUMO
Per- and polyfluoroalkyl substances (PFAS) have been shown to penetrate the blood-brain barrier (BBB) and accumulate in human brain. The BBB transmission and accumulation efficiency of PFAS, as well as the potential health risks from human co-exposure to legacy and emerging PFAS due to differences in transport efficiency, need to be further elucidated. In the present pilot study, 23 plasma samples from glioma patients were analyzed for 17 PFAS. The concentrations of PFAS in six paired brain tissue and plasma samples were used to calculate the BBB transmission efficiency of PFAS (RPFAS). This RPFAS analysis was conducted with utmost care and consideration amid the limited availability of valuable paired samples. The results indicated that low molecular weight PFAS, including short-chain and emerging PFAS, may have a greater potential for accumulation in brain tissue than long-chain PFAS. As an alternative to perfluorooctane sulfonic acid (PFOS), 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) exhibited brain accumulation potential similar to that of PFOS, suggesting it may not be a suitable substitute concerning health risk in brain. The BBB transmission efficiencies of perfluorooctanoic acid, PFOS, and 6:2 Cl-PFESA showed similar trends with age, which may be an important factor influencing the entry of exogenous compounds into the brain. A favorable link between perfluorooctane sulfonamide (FOSA) and the development and/or progression of glioma may be implicated by a strong positive correlation (r2 = 0.94; p < 0.01) between RFOSA and Ki-67 (a molecular marker of glioma). However, a causal relationship between RFOSA and glioma incidence were not established in the present study. The present pilot study conducted the first examination of BBB transmission efficiency of PFAS from plasma to brain tissue and highlighted the importance of reducing and/or controlling exposure to PFAS.
Assuntos
Barreira Hematoencefálica , Fluorocarbonos , Humanos , Barreira Hematoencefálica/metabolismo , Projetos Piloto , Fluorocarbonos/sangue , Pessoa de Meia-Idade , Feminino , Adulto , Masculino , Glioma , Idoso , Poluentes Ambientais/sangue , Exposição Ambiental , Ácidos Alcanossulfônicos/sangue , Encéfalo/metabolismoRESUMO
Objective: Glioblastoma is the most common and aggressive type of the central nervous system cancers. Although radiotherapy and chemotherapy are used in the treatment of glioblastoma, survival rates remain unsatisfactory. This study aimed to explore differentially expressed genes (DEGs) based on the survival prognosis of patients with glioblastoma and to establish a model for classifying patients into different risk groups for overall survival. Methods: DEGs from 160 tumor samples from patients with glioblastoma and 5 nontumor samples from other patients in The Cancer Genome Atlas database were identified. Functional enrichment analysis and a protein-protein interaction network were used to analyze the DEGs. The prognostic DEGs were identified by univariate Cox regression analysis. We split patient data from The Cancer Genome Atlas database into a high-risk group and a low-risk group as the training data set. Least absolute shrinkage and selection operator and multiple Cox regression were used to construct a prognostic risk model, which was validated in a test data set from The Cancer Genome Atlas database and was analyzed using external data sets from the Chinese Glioma Genome Atlas database and the GSE74187 and GSE83300 data sets. Furthermore, we constructed and validated a nomogram to predict survival of patients with glioblastoma. Results: A total of 3572 prognostic DEGs were identified. Functional analysis indicated that these DEGs were mainly involved in the cell cycle and focal adhesion. Least absolute shrinkage and selection operator regression identified 3 prognostic DEGs (EFEMP2, PTPRN, and POM121L9P), and we constructed a prognostic risk model. The receiver operating characteristic curve analysis showed that the areas under the curve were 0.83 for the training data set and 0.756 for the test data set. The predictive performance of the prognostic risk model was validated in the 3 external data sets. The nomogram showed that the prognostic risk model was reliable and that the accuracy of predicting survival in each patient was high. Conclusion: The prognostic risk model can effectively classify patients with glioblastoma into high-risk and low-risk groups in terms of overall survival rate, which may help select high-risk patients with glioblastoma for more intensive treatment.
RESUMO
High-rise buildings often use mechanical systems to assist ventilation to maintain the stability of their internal environments, and the energy consumption of mechanical ventilation poses a great challenge to urban environments and energy systems. The ventilation system of termite mounds with a combination of internal main and attached chambers is one of the classic examples of nature's bionic approach to maintaining a stable internal ventilation environment for large-volume structures. In this study, based on the inspiration of the internal ventilation chamber structure of bionic termite mounds, we constructed seven high-rise building chamber ventilation models based on the chamber structure of termite mounds with main chambers, main chambers plus single-attached chambers (three types), and main chambers plus double-attached chambers (three types) under natural ventilation conditions, aiming at obtaining the optimal low-energy and high-efficiency chamber ventilation model for bionic termite mounds in high-rise buildings. (1) The wind speed and wind pressure of the high-rise building with the addition of the bionic termite mound chamber structure is higher than that of the traditional chamber-free high-rise building in the sample floors, the maximal difference of the wind speed between the two models is 0.05 m/s, and the maximal difference of the wind speed of the single building is 0.14 m/s, with the maximal difference of the wind speed of the single building being 0.14 m/s; and the natural ventilation environment can be satisfied by a high-rise building with a chamber. (2) After increasing the single-attached chamber structure of the bionic termite mound, the difference in wind speed of different floors is 0.15 m/s, which is 0.10 m/s higher than that of the high-rise building model with the main chamber only. (3) Under the bionic termite mound chamber high-rise building double-attached chamber model, the maximum difference in wind speed of each floor sampling point can reach 0.19 m/s, while the wind pressure cloud map shows a stable wind environment system. (4) Two attached chambers are added at A and B of the high-rise building to form the a4 model of the chamber of the high-rise building with a double-chamber bionic termite mound. According to the results, it can be seen that the model of the nine floor sampling points of the maximum wind speed difference has six places for the highest value, and the single building wind speed difference for the minimum value of 0.10 m/s. The study aims to optimize the connectivity and ventilation performance of high-rise buildings under natural ventilation conditions and to promote the green and sustainable design of high-rise buildings.
RESUMO
Aphis glycines Matsumura (Hemiptera: Aphididae) is a major soybean pest that often poses a serious threat to soybean production. Imidacloprid is one of the commonly used insecticides to control the soybean aphid. To investigate the effect of termination of imidacloprid stress on the adaptive strategies of soybean aphid populations, we studied the growth, development, and related metabolism changes when the stress was terminated after 24 generations of imidacloprid stress on A. glycines. The results show that the A. glycines population accelerated its recovery and expanded its population size across generations. The longevity of the adults of the recovering population in the F12, F18, and F24 generations, respectively, was 1.11, 1.15, and 1.11 times longer than the control, while the fecundity was 10.38%, 11.74%, and 11.61% higher than that of the control. The net reproductive rate (R 0) of the recovering population was always significantly higher than that of the control in the F1 to F24 generations. In addition, metabolisms related to the regulation of cell proliferation and oocyte meiosis were significantly upregulated in the recovering population. Even when the imidacloprid pressure disappeared, intergenerational stimuli still affected the adaptive strategies of soybean aphid populations. This effect was manifested as inhibiting the growth and development of the soybean aphid in the early generations and improving the fecundity of the soybean aphid in the later generations. Adaptive soybean aphid populations would surge in the absence of imidacloprid pressure. This study provides an important reference for exploring the adaptability of the A. glycines population under termination of stress from low lethal concentrations of imidacloprid across generations. It also provides important data for monitoring the population dynamics of A. glycines in the field and analyzing the degree of pharmacodynamic stress.
RESUMO
Commercially-supplied potato galactan (PG) is widely used as a model polysaccharide in various bioactivity studies. However, results using this galactan are not always consistent with the stated composition. Here, we assessed its composition by fractionating this commercial PG and purified its primary components: PG-A, PG-B and PG-Cp with weight-averaged molecular weights of 430, 93, and 11.3 kDa, respectively. PG-Cp consists of free ß-1,4-galactan chains, whereas PG-A and PG-B are type I rhamnogalacturonans with long ß-1,4-galactan side chains of up to 80 Gal residues and short ß-1,4-galactan side chains of 0 to 3 Gal residues that display a "trees in lawn" pattern. Structures of these polysaccharides correlate well with their activities in terms of galectin-3 binding and gut bacterial growth assays. Our study clarifies the confusion related to commercial PG, with purified fractions serving as better model polysaccharides in bioactivity investigations.
Assuntos
Galactanos , Solanum tuberosum , Galactanos/química , Solanum tuberosum/química , Pectinas/química , Polissacarídeos/química , Galectina 3/metabolismoRESUMO
Information on molecular mechanisms has implicated potential association between the concentrations of heavy metals and incidences of glioma, but experimental data on human brain tissue remain sparse. To address this data gap, 13 heavy metals were measured in 137 glioma and 35 non-glioma samples collected from 161 alive patients in Guangdong Province, China in 2019 - 2020. All target heavy metals were detected, suggesting they could cross the blood-brain barrier. Concentrations of Mn, Cu, and Zn were higher in glioma than in non-glioma samples, while those of Ni and Se were higher in non-glioma samples, probably suggesting that these five heavy metals are more prone to be altered by changing pathological conditions. In addition, Cu/Zn, Cr/Mn, Cr/Se, Ni/Se, Pb/Mn, and Pb/Se were statistically different between glioma and non-glioma samples by a difference test and a multiple logistic regression model. These concentration ratios may serve as chemical markers to assist pathological analysis for differentiating between tumor and healthy tissues. However, no direct link between heavy metal concentrations or concentration ratios and biomarkers of glioma (i.e., tumor grade, P53, and Ki-67) was observed. No sufficient evidence was obtained to implicate the role of heavy metals in inducing glioma, largely caused by the limited number of samples. Different concentrations and concentration ratios of heavy metals may be the consequence rather than the cause of pathological changes in brain tumors.
Assuntos
Metais Pesados , Neoplasias , Humanos , Lacunas de Evidências , Chumbo/análise , Monitoramento Ambiental , Metais Pesados/toxicidade , Metais Pesados/análise , China , Biomarcadores , Medição de RiscoRESUMO
Data on the occurrences of legacy and alternative per- and polyfluoroalkyl substances (PFASs) in glioma are scarce. It remains unclear if PFASs exposure is related to the prevalence of glioma. A total of 137 glioma and 40 non-glioma brain tissue samples from patients recruited from the Nanfang Hospital, South China were analyzed for 17 PFAS compounds. Perfluorohexanoic acid, perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorooctane sulfonamide (FOSA), and 6:2 chlorinated polyfluorinated ether sulfonate were frequently detected (> 60 %) in glioma. The total concentrations (range; median) of 17 PFASs in glioma (0.20-140; 3.1 ng g-1) were slightly higher than those in non-glioma (0.35-32; 2.2 ng g-1), but without statistical significance. The PFAS concentrations in males were statistically higher (p < 0.05) than those in females. Elevated glioma grades were associated with higher concentrations of PFOA, PFOS, and FOSA. Positive correlations were observed between PFAS concentrations (especially for PFOA) and Ki-67 or P53 expression, pathological molecular markers of glioma. Our findings suggested that exposure to PFASs might increase the probability to develop glioma. This is the first case study demonstrating associations between PFASs exposure and brain cancer. More evidences and potential pathogenic mechanisms warranted further investigations.
Assuntos
Ácidos Alcanossulfônicos , Poluentes Ambientais , Fluorocarbonos , Ácidos Alcanossulfônicos/análise , Caprilatos , China , Éteres , Feminino , Fluorocarbonos/análise , Humanos , Antígeno Ki-67 , Masculino , Sulfonamidas , Proteína Supressora de Tumor p53RESUMO
Background: Gastric cancer (GC) is a digestive system tumor with high morbidity and mortality. It is urgently required to identify genes to elucidate the underlying molecular mechanisms. The aim of this study is to identify the key genes which may affect the prognosis of GC patients and be a therapeutic strategy for GC patients by bioinformatic analysis. Methods: The significant prognostic differentially expressed genes (DEGs) were screened out from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) datasets. The protein-protein interaction (PPI) network was established by STRING and screening key genes by MCODE and CytoNCA plug-ins in Cytoscape. Functional enrichment analysis, construction of a prognostic risk model, and nomograms verify key genes as potential therapeutic targets. Results: In total, 997 genes and 805 genes were related to the prognosis of GC in the GSE84437 and TCGA datasets, respectively. We define the 128 genes shared by the two datasets as prognostic DEGs (P-DEGs). Then, the first four genes (MYLK, MYL9, LUM, and CAV1) with great node importance in the PPI network of P-DEGs were identified as key genes. Independent prognostic risk analysis found that patients with high key gene expression had a poor prognosis, excluding their age, gender, and TNM stage. GO and KEGG enrichment analyses showed that key genes may exert influence through the PI3K-Akt pathway, in which extracellular matrix organization and focal adhesion may play important roles in key genes influencing the prognosis of GC patients. Conclusion: We found that MYLK, MYL9, LUM, and CAV1 are potential and reliable prognostic key genes that affect the invasion and migration of gastric cancer.
RESUMO
BACKGROUND: Pleomorphic xanthoastrocytoma (PXA), anaplastic pleomorphic xanthoastrocytoma (A-PXA), and epithelioid glioblastoma (E-GBM) show overlapping features. However, little is known about their clinical characteristics, molecular features and relationship with progression. METHODS: Fourteen patients diagnosed at Nanfang Hospital from 2016 to 2019 were enroled, including eleven PXA patients, two A-PXA patients, and one E-GBM patient. All tumour tissue samples of the fourteen patients were examined by immunohistochemical staining (MGMT, VEGF, BRAF-V600E, etc.). RESULTS: The mean age of 13 patients with PXA or A-PXA was 25.4 years; twelve of these patients had tumours at supratentorial regions. VEGF positivity was detected in the tumour samples of 13 patients, MGMT positivity in 10 patients, and BRAF-V600E positivity in 7 patients. The recurrent tumour tissue of the patient with E-GBM arising from A-PXA was screened to detect 11 glioma markers (MGMT, BRAF-V600E, etc.) and chromosome 1p/19q by next-generation sequencing (NGS). For the tumour sample of the E-GBM patient who survived for up to 11 years after the fourth resection, BRAF V600E was wild type in the sample obtained from the first surgery, while it was mutant in the second, third, and fourth surgeries. In contrast, the promoter status of MGMT in the four surgeries was unmethylated. The NGS results showed that the mutation frequencies of BRAF V600E in the second, third and fourth surgeries were 14.06%, 9.13% and 48.29%, respectively. CONCLUSIONS: Collectively, the results suggest that patients with A-PXA may relapse multiple times and eventually progress to E-GBM with the BRAF-V600E mutation.
Assuntos
Astrocitoma , Neoplasias Encefálicas , Glioblastoma , Adolescente , Astrocitoma/genética , Astrocitoma/patologia , Astrocitoma/cirurgia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Glioblastoma/genética , Glioblastoma/patologia , Glioblastoma/cirurgia , Humanos , Mutação , Recidiva Local de Neoplasia/genética , Proteínas Proto-Oncogênicas B-raf/genética , Fator A de Crescimento do Endotélio VascularRESUMO
Electroacupuncture (EA) is considered to have a therapeutic effect in the relief of irritable bowel syndrome (IBS)-associated visceral hypersensitivity via the reduction of the level of 5-hydroxytryptamine (5-HT) and 5-HT3 receptors (5-HT3R). However, whether Epac1/Piezo2, as the upstream of 5-HT, is involved in this process remains unclear. We investigated whether EA at the ST36 and ST37 acupoints alleviated visceral and somatic hypersensitivity in a post-inflammatory IBS (PI-IBS) model mice via the Epac1-Piezo2 axis. In this study, we used 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced PI-IBS as a mouse model. Visceral sensitivity was assessed by the abdominal withdrawal reflex test. Somatic sensitivity was evaluated by the hind paw withdrawal threshold. Quantitative real-time PCR, immunofluorescence staining, ELISA, and Western blotting were performed to examine the expressions of Epac1, Piezo2, 5-HT, and 5-HT3R from the mouse distal colon/L5-S2 dorsal root ganglia (DRG). Our results showed that EA improved the increased visceral sensation and peripheral mechanical hyperalgesia in PI-IBS model mice, and the effects of EA were superior to the sham EA. EA significantly decreased the protein and mRNA levels of Epac1 and Piezo2, and reduced 5-HT and 5-HT3R expressions in the distal colon. Knockdown of colonic Piezo2 eliminated the effect of EA on somatic hypersensitivity. Combined knockdown of colonic Epac1 and Piezo2 synergized with EA in relieving visceral hypersensitivity and blocked the effect of EA on somatic hypersensitivity. Additionally, protein levels of Epac1 and Piezo2 were also found to be decreased in the L5-S2 DRGs after EA treatment. Taken together, our study suggested that EA at ST36 and ST37 can alleviate visceral and somatic hypersensitivity in PI-IBS model mice, which is closely related to the regulation of the Epac1-Piezo2 axis.
Assuntos
Eletroacupuntura , Fatores de Troca do Nucleotídeo Guanina , Canais Iônicos , Síndrome do Intestino Irritável , Animais , Fatores de Troca do Nucleotídeo Guanina/genética , Hiperalgesia/etiologia , Hiperalgesia/metabolismo , Hiperalgesia/terapia , Canais Iônicos/genética , Síndrome do Intestino Irritável/terapia , Camundongos , Serotonina/metabolismoRESUMO
Background: Glioblastoma (GBM) is the most common and malignant type of brain tumor. A large number of studies have shown that the immunotherapy of tumors is effective, but the immunotherapy effect of GBM is not poor. Thus, further research on the immune-related hub genes of GBM is extremely important. Methods: The GBM highly correlated gene clusters were screened out by differential expression, mutation analysis, and weighted gene co-expression network analysis (WGCNA). Least absolute shrinkage and selection operator (LASSO) and proportional hazards model (COX) regressions were implemented to construct prognostic risk models. Survival, receiver operating characteristic (ROC) curve, and compound difference analyses of tumor mutation burden were used to further verify the prognostic risk model. Then, we predicted GBM patient responses to immunotherapy using the ESTIMATE algorithm, GSEA, and Tumor Immune Dysfunction and Exclusion (TIDE) algorithm. Results: A total of 834 immune-related differentially expressed genes (DEGs) were identified. The five hub genes (STAT3, SEMA4F, GREM2, MDK, and SREBF1) were identified as the prognostic risk model (PRM) screened out by WGCNA and LASSO analysis of DEGs. In addition, the PRM has a significant positive correlation with immune cell infiltration of the tumor microenvironment (TME) and expression of critical immune checkpoints, indicating that the poor prognosis of patients is due to TIDE. Conclusion: We constructed the PRM composed of five hub genes, which provided a new strategy for developing tumor immunotherapy.
RESUMO
Objective: To investigate the correlation between Chinese medicine syndrome and cognitive dysfunction in patients with mild cognitive impairment (MCI). Methods: 121 MCI patients were included for syndrome differentiation and syndrome scoring according to the Chinese medicine syndrome classification standard of senile dementia. The cognitive function and cognitive subitems (including visual space and executive function, naming, attention, language, abstraction, delayed recall, and orientation) of patients with different Chinese medicine syndromes were scored with the Montreal Cognitive Assessment (MoCA). Correlation analysis was made on Chinese medicine syndromes and cognitive domain damage. Results: Chinese medicine syndromes from most to least were kidney deficiency and marrow reduction syndrome, turbid phlegm obstructing orifices syndrome, deficiency of heart and spleen syndrome, qi stagnation and blood stasis syndrome, and yin deficiency of heart and liver syndrome. There were no significant differences in MoCA scores among different Chinese medicine syndromes (P > 0.05).In the kidney deficiency and marrow reduction syndrome, the delayed recall score was 1.74 ± 1.23 and the difference was statistically significant when compared with deficiency of heart and spleen syndrome or the yin deficiency of heart and liver syndrome (P < 0.05). In the turbid phlegm obstructing orifices syndrome, the delayed recall score was 1.81 ± 1.33 and the difference was statistically significant when compared with the yin deficiency of heart and liver syndrome (P < 0.05). There was a significant negative correlation between the kidney deficiency and marrow reduction syndrome's Chinese medicine syndrome scores and MoCA scores (P < 0.01), and there was a negative correlation between the turbid phlegm obstructing orifices syndrome's Chinese medicine syndrome scores and MoCA scores (P < 0.05). Correlation analysis showed that the kidney deficiency and marrow reduction syndrome was significantly negatively correlated with delayed recall scores (P < 0.01), and it was also negatively correlated with visual space and executive function scores (P < 0.05). The turbid phlegm obstructing orifices syndrome was significantly negatively correlated with delayed recall scores (P < 0.01). Conclusion: The kidney deficiency and marrow reduction syndrome and the turbid phlegm obstructing orifices syndrome were the most common syndromes in MCI. Patients with kidney deficiency and marrow reduction syndrome might have obvious damage in delayed recall function and have damage in visual space and executive function. Patients with turbid phlegm obstructing orifices syndrome might have obvious damage in delayed recall function.
RESUMO
Polysaccharides from fungi have many bioactivities. Previous studies showed that galactomannans from Penicillium oxalicum antagonize galectin-8-mediated activity. Here, two intracellular and two extracellular galactomannans were purified and their structures were comparatively characterized by NMR, partial acid hydrolysis and methylation. All four of them were identified to be galactomannans with similar mannan backbones having 1,2-/1,6-linkages (~3:1) and various amounts of galactofuranan side chains. The interaction of those polysaccharides with galectin-8 was assessed by hemagglutination and biolayer interferometry. These results show that side chains are important for the interaction, and the more the side chains, the stronger the interaction. But the side chains alone did not show act on galectin-8, which indicated that the cooperation between backbone and side chains is another necessary factor for this interaction. Our findings provide important information about structure-activity relationships and the galactofuranose-containing galactomannans might be as potential therapeutic of galectin-8 related diseases.
Assuntos
Mananas , Penicillium , Galactose/análogos & derivados , Galectinas , Mananas/química , Mananas/farmacologia , Polissacarídeos/químicaRESUMO
BACKGROUND: Compared with the proneural (PN) subtype of glioblastoma (GBM), the mesenchymal (MES) subtype is more invasive and immune evasive and is closely related to poor prognosis. Here, we used transcriptome data and experimental evidence to indicate that CUB domain-containing protein 1 (CDCP1) is a novel regulator that facilitates the transformation of PN-GBM to MES-GBM. METHODS: The mRNA expression data of CDCP1 in glioma were collected from the TCGA, CGGA and GEO databases, and in vitro experiments verified CDCP1 expression in glioma tissue samples. Independent prognostic analysis revealed the correlation of the CDCP1 expression level and patient survival. Bioinformatics analysis and experiments verified the biological function of CDCP1. Multivariate proportional hazards models and a PPI network were used to select key genes. A prognostic risk model for predicting the survival of glioma patients was constructed based on the selected genes. RESULTS: The results showed that the expression of CDCP1 increased with increasing tumor grade and that the overexpression of CDCP1 correlated with a poor prognosis. CDCP1 was highly expressed in MES-GBM but weakly expressed in PN-GBM. The risk model (considering CDCP1 combined with CD44 and ITGAM expression) could represent a tool for predicting survival and prognosis in glioma patients. CONCLUSIONS: Our study indicates that CDCP1 plays an important role in facilitating the transformation of PN-GBM to MES-GBM.
RESUMO
Epithelioid glioblastoma (E-GBM) is a recently described variant of glioblastoma (GBM) which is associated with short survival and now added as a provisional entity to WHO 2016 classification of central nervous system tumors. About half of these tumors show the BRAF mutant. Therefore, this is a target of special interest for this group of patients. Meanwhile, unlike conventional glioblastoma, E-GBM lacks specific prognostic markers. We described a case of a long-term surviving 37-years-old men patient diagnosed with a BRAF V600E and TERT mutated E-GBM with wild-type in the isocitrate dehydrogenase gene (IDH wild-type). The tumor displayed atypical exophytic growth, an obvious proliferation of vascular endothelial cells, especially tumor tissue can be seen under subarachnoid space. Notably, tumor tissue was found under subarachnoid space. After postoperative conventional treatment options were exhausted, vemurafenib treatment was initiated. The patient remained clinically stable, and follow-up magnetic resonance images were consistent with stable disease for the following fifteen months up to now. Whole-exome sequencing analysis and RNA-seq results of formalin-fixed and paraffin-embedded tissue revealed nine mutant genes (AHNAK2, BFSP1, BRAF, CNTNAP3, DNHD1, MTOR, NFATC3, NOM1). For E-GBM patients, the use of BRAF inhibitors combined with inhibitors of these seven genes may be a useful remedial treatment option.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Vemurafenib/uso terapêutico , Adulto , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Glioblastoma/genética , Glioblastoma/patologia , Humanos , Masculino , Proteínas Proto-Oncogênicas B-raf/genética , Telomerase/genética , Sequenciamento do ExomaRESUMO
Human brain has a complex structure and is able to perform powerful functions. Blood-brain barrier blocks the entry of foreign substances and maintains the homeostasis of the brain. However, some exogenous substances are still able to pass through the blood-brain barrier, with distribution patterns yet to be clarified. Perfluoroalkyl and polyfluoroalkyl substances (PFASs), including perfluoroalkyl carboxylic acids (PFCAs), perfluoroalkyl sulfonic acids (PFSAs), a precursor (perfluorooctane sulfonamide that can be degraded to other substances), and emerging PFASs, were analyzed for the first time in living human brain glioma. The target compounds were detected and quantified in 25 out of 26 glioma samples. The concentration range of ∑PFAS was < RL-51 ng g-1 wet weight (applied to all reported concentrations), with a median of 2.9 ng g-1. The most abundant compound was PFCAs (40%), followed by PFSAs (28%), emerging PFASs (22%), and perfluorooctane sulfonamide (10%). Abundant alternatives PFASs, including short-chain PFCAs, short-chain PFSAs, and emerging PFASs (52% of ∑PFAS), were found in the glioma samples, supporting the notion that low molecular weight exogenous compounds have high permeability to cross the blood-brain barrier and accumulate in brain tissue. Gender difference was not significant (p > 0.05) in the concentrations of PFASs in the glioma samples. Concentrations of PFASs increased with increasing age, from 0.61 ng g-1 (0-14 years old) to 1.6 ng g-1 (>48 years old), with no significant linear correlation with age. The present study suggested that glioma is an effective indicator for monitoring exogenous contaminants in brain tissues.
Assuntos
Ácidos Alcanossulfônicos , Fluorocarbonos , Glioma , Poluentes Químicos da Água , Adolescente , Ácidos Alcanossulfônicos/análise , Encéfalo , Criança , Pré-Escolar , Monitoramento Ambiental , Fluorocarbonos/análise , Humanos , Lactente , Recém-Nascido , Pessoa de Meia-Idade , Poluentes Químicos da Água/análiseRESUMO
BACKGROUND: Frontal glioma frequently invaded the subventricular zone (SVZ), which existed glioma stem cells and might be involved in the development of primary and recurrent gliomas. We attempted to identify whether ventricle wall resection contributed to the maximal extent of resection (EOR) and increased the patient's survival during frontal glioma resection. METHODS: A total of 151 adult patients with primary SVZ-involved frontal gliomas were obtained between January 2012 and December 2018. We analyzed clinical data, EOR, complications and survival profiles between the ventricle wall group and the ventricle intact/opening group. RESULTS: Applying ventricle wall removal had similar effect on the improvement of neurological function compared to applying ventricle intact/opening and did not increase the incidence of new neurological deficits, hydrocephalus, and ependymal dissemination in SVZ-involved frontal gliomas. A positive correlation was identified between EOR and the ventricle wall handling (r = 0.487, P < 0.001), which indicated that ventricle wall resection could contribute to achieve supramaximal resection. Applying supramaximal resection and ventricle wall resection could significantly prolong overall survival and progression free survival. Ventricle wall resection could be regarded as an independent prognostic indicator for both overall survival and progression free survival in patients with SVZ-involved frontal gliomas. CONCLUSIONS: Ventricle wall resection in SVZ-involved frontal gliomas could contribute to achieve supramaximal resection and could significantly prolong overall survival and progression free survival.
Assuntos
Neoplasias Encefálicas/cirurgia , Glioma/cirurgia , Ventrículos Laterais/cirurgia , Adolescente , Adulto , Idoso , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/mortalidade , Feminino , Glioma/diagnóstico , Glioma/mortalidade , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Adulto JovemRESUMO
BACKGROUND: Intraventricular penetration is rare in glioblastoma (GBM). Whether the ependymal region including the ependyma and subventricular zone (SVZ) can prevent GBM invasion remains unclear. METHODS: Magnetic resonance imaging (MRI) and haematoxylin-eosin (HE) staining were performed to evaluate the size and anatomical locations of GBM. Binary logistic regression analysis was used to assess the correlation between tumor-ependyma contact, ventricle penetration and clinical characteristics. Cell migration and invasion were assessed via Transwell assays and an orthotopic transplantation model. RESULTS: Among 357 patients with GBM, the majority (66%) showed ependymal region contact, and 34 patients (10%) showed ventricle penetration of GBM. GBM cells were spread along the ependyma in the orthotopic transplantation model. The longest tumor diameter was an independent risk factor for GBM-ependymal region contact, as demonstrated by univariate (OR = 1.706, p < 0.0001) and multivariate logistic regression analyses (OR = 1.767, p < 0.0001), but was not associated with ventricle penetration. Cerebrospinal fluid (CSF) could significantly induce tumor cell migration (p < 0.0001), and GBM could grow in CSF. Compared with those from the cortex, cells from the ependymal region attenuated the invasion of C6 whether cocultured with C6 or mixed with Matrigel (p = 0.0054 and p = 0.0488). Immunofluorescence analysis shows a thin gap with GFAP expression delimiting the tumor and ependymal region. CONCLUSION: The ependymal region might restrict GBM cells from entering the ventricle via a non-mechanical force. Further studies in this area may reveal mechanisms that occur in GBM patients and may enable the design of new therapeutic strategies.