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1.
Medicine (Baltimore) ; 98(39): e17130, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574813

RESUMO

Animal studies have demonstrated that autophagy was involved in neuronal damage after intracerebral hemorrhage (ICH). Several studies showed thrombin-antithrombin (TAT) plasma levels were elevated in patients with ICH. In this study, we aimed to evaluate if autophagy occurred in patients with ICH; and the relationship between the severity of brain injury and plasma TAT levels.A novel tissue harvesting device was used during hematoma removal surgery to collect loose fragments of tissue surrounding the affected brain area in 27 ICH patients with hematoma volumes of >30 mL in the basal ganglia. Control tissues were obtained from patients who underwent surgery for arteriovenous malformation (n = 25). Transmission electron microscopy (TEM) and immunohistochemistry for autophagy-related proteins were used to evaluate the ultrastructural and morphologic cellular characteristics; and the extent of autophagy in the recovered tissue specimens. Stroke severity was assessed by using the Glasgow Coma Scale (GCS) and the National Institutes of Health Stroke Scale (NIHSS). An enzyme-linked immunosorbent assay (ELISA) was used to measure plasma TAT levels.Transmission electron microscopy showed autophagosomes and autolysosomes exist in neurons surrounding the hematoma, but not in the control tissues. The number of cells containing autophagic vacuoles correlated with the severity of brain injury. Immunohistochemistry showed strong LC3, beclin 1, and cathepsin D staining in ICH tissue specimens. Plasma TAT levels correlated positively with autophagic cells and ICH severity (P < .01).Autophagy was induced in perihematomal neurons after ICH. Autophagy and plasma TAT levels correlated positively with severity of brain injury. These results suggest that autophagy and increased plasma TAT levels may contribute to the secondary damage in ICH patients.


Assuntos
Autofagia , Hemorragia Cerebral/sangue , Hematoma/sangue , Neurônios/fisiologia , Peptídeo Hidrolases/sangue , Adulto , Idoso , Antitrombina III , Gânglios da Base/metabolismo , Hemorragia Cerebral/fisiopatologia , Hemorragia Cerebral/cirurgia , Feminino , Escala de Coma de Glasgow , Hematoma/fisiopatologia , Hematoma/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade
2.
Artif Cells Nanomed Biotechnol ; 47(1): 250-255, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30663389

RESUMO

Flotillin-2 (FLOT2) was reported as oncogene and involves in the pathogenic process of several cancers, yet the precise mechanism of FLOT2 in glioma is still limited. In this study, we demonstrated that FLOT2 expression levels were greatly upregulated in glioma tissues and cell lines, and the FLOT2 expression in glioma tissue was markedly associated with tumour stage and size. Overexpression of FLOT2 was correlated with poor prognosis of glioma patients. The functional assay revealed that silenced FLOT2 repressed the viability, migration, and invasion of glioma cells. And then, we detected the relationship between miR-449 and FLOT2. Luciferase reporter assay and Western blot results showed that miR-449 directly binding the 3'UTR sequence of FLOT2 and regulated FLOT2 expression in glioma cells. Finally, we detected the expression levels of miR-449 in glioma tissue and cell lines and found that miR-449 was significantly downregulated in glioma tissues and cell lines. In conclusion, we demonstrated that overexpression FLOT2 was associated with poor prognosis of glioma patients and involved in the progression of glioma, identifying a novel prognostic biomarker and therapeutic target for glioma progression.


Assuntos
Biomarcadores Tumorais/genética , Glioma/diagnóstico , Glioma/genética , Proteínas de Membrana/genética , MicroRNAs/genética , Regiões 3' não Traduzidas/genética , Biomarcadores Tumorais/deficiência , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Sobrevivência Celular/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Inativação Gênica , Glioma/patologia , Humanos , Masculino , Proteínas de Membrana/deficiência , Pessoa de Meia-Idade , Invasividade Neoplásica , Regulação para Cima/genética
3.
J Neurosurg ; 129(3): 583-592, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29099300

RESUMO

OBJECTIVE Glioma is the most common form of brain tumor and has high lethality. The authors of this study aimed to elucidate the efficiency of preoperative inflammatory markers, including neutrophil/lymphocyte ratio (NLR), derived NLR (dNLR), platelet/lymphocyte ratio (PLR), lymphocyte/monocyte ratio (LMR), and prognostic nutritional index (PNI), and their paired combinations as tools for the preoperative diagnosis of glioma, with particular interest in its most aggressive form, glioblastoma (GBM). METHODS The medical records of patients newly diagnosed with glioma, acoustic neuroma, meningioma, or nonlesional epilepsy at 3 hospitals between January 2011 and February 2016 were collected and retrospectively analyzed. The values of NLR, dNLR, PLR, LMR, and PNI were compared among patients suffering from glioma, acoustic neuroma, meningioma, and nonlesional epilepsy and healthy controls by using nonparametric tests. Correlations between NLR, dNLR, PLR, LMR, PNI, and tumor grade were analyzed. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic significance of NLR, dNLR, PLR, LMR, PNI, and their paired combinations for glioma, particularly GBM. RESULTS A total of 750 patients with glioma (Grade I, 81 patients; Grade II, 208 patients; Grade III, 169 patients; Grade IV [GBM], 292 patients), 44 with acoustic neuroma, 271 with meningioma, 102 with nonlesional epilepsy, and 682 healthy controls were included in this study. Compared with healthy controls and patients with acoustic neuroma, meningioma, or nonlesional epilepsy, the patients with glioma had higher values of preoperative NLR and dNLR as well as lower values of LMR and PNI, whereas PLR was higher in glioma patients than in healthy controls and patients with nonlesional epilepsy. Subgroup analysis revealed a positive correlation between NLR, dNLR, PLR, and tumor grade but a negative correlation between LMR, PNI, and tumor grade in glioma. For glioma diagnosis, the area under the curve (AUC) obtained from the ROC curve was 0.722 (0.697-0.747) for NLR, 0.696 (0.670-0.722) for dNLR, 0.576 (0.549-0.604) for PLR, 0.760 (0.738-0.783) for LMR, and 0.672 (0.646-0.698) for PNI. The best diagnostic performance was obtained with the combination of NLR+LMR and dNLR+LMR, with AUCs of 0.777 and 0.778, respectively. Additionally, NLR (AUC 0.860, 95% CI 0.832-0.887), dNLR (0.840, 0.810-0.869), PLR (0.678, 0.641-0.715), LMR (0.837, 0.811-0.863), and PNI (0.740, 0.706-0.773) had significant predictive value for GBM compared with healthy controls and other disease groups. As compared with the Grade I-III glioma patients, the GBM patients had an AUC of 0.811 (95% CI 0.778-0.844) for NLR, 0.797 (0.763-0.832) for dNLR, 0.662 (0.622-0.702) for PLR, 0.743 (0.707-0.779) for LMR, and 0.661(0.622-0.701) for PNI. For the paired combinations, NLR+LMR demonstrated the highest accuracy. CONCLUSIONS The NLR+LMR combination was revealed as a noninvasive biomarker with relatively high sensitivity and specificity for glioma diagnosis, the differential diagnosis of glioma from acoustic neuroma and meningioma, GBM diagnosis, and the differential diagnosis of GBM from low-grade glioma.


Assuntos
Neoplasias Encefálicas/cirurgia , Glioma/cirurgia , Mediadores da Inflamação/sangue , Cuidados Pré-Operatórios , Estudos de Coortes , Humanos
4.
J Neurooncol ; 127(2): 355-62, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26725096

RESUMO

Gliosarcoma (GSM) is a rare biphasic neoplasms of the central nervous system composed of a glioblastoma multiforme (GBM) admixed with a sarcomatous component. In clinical practice GSM is generally managed similarly to GBM. However, there are conflicting reports regarding their clinical aggressiveness, cell line of origin and possible prognosis compared with those of GBM. The objective of this study was to compare clinic-pathological features in GSM patients with the GBM patients during the same study period. 518 patients with GBM were treated at our hospital between 2008 and 2013, among them 51 were GSM. In this series the GSMs represented 9.8% of all GBMs and included 58.8% male with a median age of 44.7 years. The locations, all supratentorial, included temporal in 41.2%, frontal in 25.5%, parietal in 19.6%, and occipital in 13.7%. All patients underwent tumor resection followed by post-operative radiation and adjuvant chemotherapy. The O6-methylguanine-DNA methyltransferase promoter methylation studies were significantly more frequent in the GBMs than GSMs (80.1% vs. 44.7%, P < 0.001). The median progression free survival and overall survival for the patients with GSM were 8.0 and 13.0 months, respectively, as compared with 9.0 and 14.0 months in the GBM group (log rank test P = 0.001 and 0.004, respectively). The Cox proportional hazards regression model indicated that the extent of tumor resection (HR = 1.518, P = 0.009) and pathological types (HR = 0.608, P = 0.002) were the significant prognostic factors in our own series. With regard to clinical features and outcomes, GSM and GBM cannot be distinguished clinically. GSM in China may be managed similarly to GBM, with maximal safe surgical resection followed by chemo-radiotherapy. Our study adds further evidence to support GSM as a unique clinical entity with a likely worse prognosis than GBM.


Assuntos
Neoplasias Ósseas/secundário , Neoplasias Encefálicas/patologia , Glioblastoma/patologia , Gliossarcoma/patologia , Adolescente , Adulto , Idoso , Neoplasias Ósseas/genética , Neoplasias Ósseas/cirurgia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/cirurgia , Criança , Pré-Escolar , China , Metilação de DNA , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Feminino , Seguimentos , Glioblastoma/genética , Glioblastoma/cirurgia , Gliossarcoma/genética , Gliossarcoma/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Regiões Promotoras Genéticas/genética , Estudos Retrospectivos , Taxa de Sobrevida , Proteínas Supressoras de Tumor/genética , Adulto Jovem
5.
Springerplus ; 4: 550, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26435896

RESUMO

Fungal sellar abscess is rare. A 42-year-old man was admitted with 2-month headache characterized by right peri-orbital pain. An intrasellar mass was found to be simulated a pituitary neoplasm after magnetic resonance imaging examination, and operated on via an endoscopic trans-sphenoidal approach. Milk-like pus and a mass of ash black mixed and necrotic material were found and removed. Histopathology revealed numerous aspergillus hyphae. Itraconazole was given on a dosage of 200 mg twice a day orally for 6 weeks. No recurrence was observed during follow-up. Complete surgical resection through endoscopic trans-sphenoidal approach combined with systemic anti-fungal therapy, should be considered as the optimal treatment.

6.
Int J Clin Exp Pathol ; 8(6): 7583-7, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26261673

RESUMO

Although previous reports purpored that the unique magnetic resonance imaging (MRI) features of Lhermitte-Duclos disease (LDD) obviates the need for biopsy, we have made a misdiagnosis of LDD which has an indistinguishable imaging appearance. We present a patient who suffered from a normal cerebellum with arachnoid vascular malformation that had imaging characteristics which were indistinguishable from LDD before operation. This atypical imaging appearance, which could potentially be confused with LDD, may lead to misdiagnosis and inappropriate treatment in the absence of tissue sampling. Thus, this finding suggests that in those patients where images are highly suggestive of LDD but lack other manifestations of Cowden syndrome, biopsy is required and advanced imaging with magnetic resonance spectroscopy (MRS) should be strongly considered.


Assuntos
Erros de Diagnóstico , Síndrome do Hamartoma Múltiplo/diagnóstico , Imagem por Ressonância Magnética , Adulto , Biópsia , Diagnóstico Diferencial , Feminino , Síndrome do Hamartoma Múltiplo/patologia , Síndrome do Hamartoma Múltiplo/cirurgia , Humanos , Valor Preditivo dos Testes
7.
Eur Neurol ; 74(1-2): 28-35, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26139100

RESUMO

Our knowledge about pathophysiology of intracerebral hemorrhage (ICH) mainly originates from preclinical models of ICH. In this study, cerebral ultrastructure surrounding hematoma and its correlation with clinical severity were investigated in ICH patients. Thirty patients with basal ganglia hemorrhage and 6 control subjects were enrolled. Surgical evacuation was performed for patients with a blood loss >30 ml. Stroke severity was assessed using the Glasgow Coma Scale (GCS) and the National Institute of Health Stroke Scale (NIHSS). Transmission electron microscopy (TEM) was used to evaluate the ultrastructural characteristics of tissue specimens. Neural cells surrounding the hematomas showed evidence of cell swelling and necrosis. Decreased numbers of organelles and mitochondrial cristae were accompanied by cytoplasmic vacuolization, nuclear membrane invagination and breakdown, and intranuclear chromatic agglutination. These changes resulted in disintegration together with malacia, disappearance of the nucleus and nucleolus, and karyopyknosis. More serious ultrastructural damage was seen in patients with greater NIHSS scores, lower GCS scores, and greater bleeding volumes (p < 0.001). These findings suggest that neural cells undergo unfavorable ultrastructural changes that are responsible for dysfunction after ICH.


Assuntos
Hemorragia dos Gânglios da Base/patologia , Encéfalo/ultraestrutura , Adulto , Idoso , Feminino , Escala de Coma de Glasgow , Hematoma/patologia , Humanos , Masculino , Microscopia Eletrônica de Transmissão , Pessoa de Meia-Idade , Acidente Vascular Cerebral/patologia
8.
Int J Antimicrob Agents ; 43(1): 68-72, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24139880

RESUMO

Cefepime is administered as an intermittent infusion (II); however, continuous infusion (CI) may be advantageous because ß-lactam antibiotics exhibit time-dependent antibacterial activity. This retrospective, non-randomised, comparative study included 68 neurosurgical patients with post-operative intracranial infections treated with 4g/day cefepime over 24h as a CI (n=34) or 2g every 12h as II (n=34). CI controlled the intracranial infection more rapidly and effectively than II (6.6±1.9 days vs. 7.8±2.6 days; P=0.036). By considering the minimum inhibitory concentrations (MICs) to be 4µg/mL and 8µg/mL, the percentage of time when the cefepime plasma or CSF concentrations were higher than the MIC (%T>MIC) was calculated for each patient. For plasma cefepime concentrations, the %T(>MIC) in the CI group was higher than in the II group (for MICs of 8µg/mL, 100% vs. 75%, respectively). The mean calculated area under the curve (AUC) in the CI group was similar to the II group (1197.99±72.15µgh/mL vs. 890.84±140.78µgh/mL; P=0.655). For CSF cefepime concentrations, the %T(>MIC) in the CI group was higher than in the II group (for MICs of 4µg/mL and 8µg/mL, 83.3% and 75% vs. 25% and 0%, respectively). The mean calculated AUC for the CI group was higher than the II group (220.56±13.59µgh/mL vs. 86.34±5.69µgh/mL; P=0.003). Therefore, CI of cefepime significantly enhanced the antibacterial effect and reduced the treatment duration in neurosurgical patients with post-operative intracranial infections.


Assuntos
Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Cefalosporinas/administração & dosagem , Cefalosporinas/farmacocinética , Meningites Bacterianas/tratamento farmacológico , Complicações Pós-Operatórias/tratamento farmacológico , Adulto , Idoso , Cefepima , Feminino , Humanos , Infusões Intravenosas/métodos , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/efeitos adversos , Plasma/química , Estudos Retrospectivos
9.
J Clin Neurosci ; 19(12): 1636-40, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23047061

RESUMO

Combining bevacizumab with irinotecan is a new chemotherapy regimen for patients with recurrent glioblastoma multiforme (GBM). Recent phase II trials suggest that this combined chemotherapy is beneficial to patients, but the subsequent adverse events may lead to treatment discontinuation. No comparison has yet demonstrated conclusively that the combined chemotherapy is more beneficial than single-agent chemotherapy. Thus, a meta-analysis was conducted to assess the efficacy and safety of bevacizumab compared to bevacizumab combined with irinotecan for the treatment of recurrent GBM. A total of 480 patients were included in the study, with 183 patients (38.1%) in the bevacizumab group and 297 patients (61.9%) in the bevacizumab plus irinotecan group. The median overall survival was 8.63 months (95% confidence interval [CI], 8.54-8.72 months) and 8.91 months (95% CI, 8.69-9.13 months), respectively. The mean objective response rate (complete response plus partial response rate) was 33.9% (95% CI, 18.1-52.1%) and 45.8% (95% CI, 28.2-66.7%), respectively. The 6-month progression-free survival rates (PFS-6) were 38.8% (95% CI, 18.8-57.0%) and 48.3% (95% CI, 25.4-54.3%), respectively. The rate of discontinuation was 5.5% and 20.0%, respectively. Compared with patients treated with bevacizumab only, those in the bevacizumab plus irinotecan group had higher PFS-6 (p=0.046), objective response (p=0.013) and rate of discontinuation (p=0.000) but there was no statistically significant difference in overall survival between the groups (p=0.487). Thus, although the combination of bevacizumab and irinotecan may increase the rate of discontinuation, it provided no obvious improvement in overall survival in patients with recurrent GBM. Therefore, the benefits of drug combination are outweighed by the treatment discontinuity and quality of life effects of drug toxicity and should be considered on an individual patient basis only.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Adolescente , Adulto , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Camptotecina/análogos & derivados , Criança , Pré-Escolar , Feminino , Humanos , Irinotecano , Masculino , Pessoa de Meia-Idade , Adulto Jovem
10.
Zhonghua Yi Xue Za Zhi ; 88(3): 174-6, 2008 Jan 15.
Artigo em Chinês | MEDLINE | ID: mdl-18361815

RESUMO

OBJECTIVE: To investigate the matrix metalloproteinase (MMP)-9 played in secondary brain injury following intracerebral hemorrhage (ICH). METHODS: Hematoma fluid and peripheral blood samples were collected from 60 ICH patients, 34 males and 26 females, aged 60 +/- 13 (37 - 81) n the days 1, 4, and 7 after evacuation of hematoma. Peripheral blood samples were collected form. 30 sex, and age-matched healthy adults as normal controls. Cerebrospinal fluid (SCF) samples were collected from 10 sex, and age-matched patients to undergo operation during lumbar anesthesia. ELISA was used to detect the content of MMP-9. Tada formula was used to calculate the perihematomal edema volume. The National Institutes of Health Stroke Scale (NIHHS) and Glasgow Coma Score (GCS) were used to assess the condition of patients. RESULTS: (1) The MMP-9 levels in the plasma and hematoma fluid of the ICH patients at all time points were all significantly higher than those of the normal controls (all P < 0.01). MMP-9 was not found in the normal CSF. (2) The plasma and hematoma fluid MMP-9 levels were increased already in the day 1, peaked in the day 4, and then kept at a high level until the day 7. (3) The MMP-9 levels in hematoma fluid t all time points were all significantly higher than those in the plasma (all P < 0.01). (4) The MMP-9 level was positively correlated with the hematoma volume and NIHSS score, and negatively correlated with the GCS score (both P < 0.01). CONCLUSIONS: MMP-9 may takes part in the secondary injury after ICH, and its change is correlated with the hydrocephalus of patients. The dynamical change of the plasma MMP-9 level is consistent with the hematoma fluid MMP-9 level after ICH. There is a positive correlation among the MMP-9 level, perihematomal edema volume, and severity of ICH.


Assuntos
Hemorragia Cerebral/sangue , Hematoma/sangue , Metaloproteinase 9 da Matriz/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
11.
Zhonghua Yi Xue Za Zhi ; 86(43): 3073-6, 2006 Nov 21.
Artigo em Chinês | MEDLINE | ID: mdl-17288840

RESUMO

OBJECTIVE: To observe the neural apoptosis and expression of apoptosis-related genes in brain in order to elucidate the regulation mechanism in the perihematomal region of intracerebral hemorrhage (ICH) patients. METHODS: Specimens of perihematomal region in human brain were obtained from 29 patients undergoing surgical evacuation of an intracerebral hematoma. Specimens of brain tissue were collected from the corpses of 6 persons within 3 hours after the accidental death. Neural apoptosis was evaluated by terminal deoxynucleotidyl transferase-mediated deoxyuridine 5' triphosphate nick end labeling (TUNEL) method and immunohistochemistry was used to detect the expression of Bcl-2, Bax, P53, and caspase-3 genes. RESULTS: The apoptosis rates of the ICH group was 4.10 +/- 0.28, significantly higher than that of the control group (0.57 +/- 0.43, P < 0.01). The expression rate of Bcl-2 the ICH group was 2.68 +/- 0.52, significantly higher than that of the control group (1.54 +/- 0.56, P < 0.01). The expression rate of Bax of the ICH group was 3.49 +/- 0.18, significantly higher than that of the control group (0.96 +/- 0.27, P < 0.01). The expression of P53 was 4.12 +/- 0.63, significantly higher than that of the control group (0.96 +/- 0.71, P < 0.01). The expression of caspase-3 of the ICH group was 3.50 +/- 0.25, significantly higher than that of the control group (0.74 +/- 0.73, P < 0.01). The expression levels of Bcl-2 and P53 were negatively correlated with the apoptosis rate (both P < 0.01), while the expression levels of Bax and caspase-3, and the Bax/Bcl-2 ratio were positively correlated with the apoptosis rate in perihematomal region of ICH patients (all P < 0.01). CONCLUSION: Apoptosis is involved in the delayed brain injury after ICH in human and is the main factor of delayed neural death. Some of the genes take part in the regulation of neural apoptosis: Bax and caspase-3 hasten the apoptosis while Bcl-2 and P53 restrain it.


Assuntos
Proteínas Reguladoras de Apoptose/biossíntese , Apoptose , Hematoma/metabolismo , Hemorragia Intracraniana Hipertensiva/metabolismo , Neurônios/metabolismo , Adulto , Idoso , Caspase 3/biossíntese , Feminino , Hematoma/patologia , Humanos , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Hemorragia Intracraniana Hipertensiva/patologia , Masculino , Pessoa de Meia-Idade , Neurônios/patologia , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Proteína Supressora de Tumor p53/biossíntese
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