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BACKGROUND: Current modalities for diagnosing carotid cavernous fistula (CCF) are inaccurate in analysing retinal microcirculations and nerve fibre changes. Retinal microvascular and neural alterations occur in CCF patients and can be quantitatively measured using optical coherence tomography angiography (OCTA). We measured the neurovascular changes in the eyes of CCF patients and used OCTA as a supplementary method. METHODS: This cross-sectional study studied 54 eyes of 27 unilateral CCF subjects and 54 eyes of 27 healthy age- and sex-matched controls. OCTA parameters in the macula and optic nerve head (ONH) were analysed using a one-way analysis of variance with further Bonferroni corrections. Parameters with statistical significance were included in a multivariable binary logistic regression analysis and receiver operating characteristic (ROC) curves were generated. RESULTS: There was significantly less deep-vessel density (DVD) and ONH-associated capillary density in both eyes of CCF patients than in controls, while the differences between the affected and contralateral eyes were insignificant. The retinal nerve fibre layer and ganglion cell complex thickness were lower in the affected eyes than in the contralateral or controlled eyes. ROC curves identified DVD and ONH-associated capillary density as significant parameters in both eyes of CCF patients. CONCLUSION: The retinal microvascular circulation was affected in both eyes of unilateral CCF patients. Microvascular alterations occurred before retinal neural damage. This quantitative study suggests a supplementary measurement for diagnosing CCF and detecting early neurovascular impairments.
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Fístula del Seno Cavernoso de la Carótida , Disco Óptico , Humanos , Tomografía de Coherencia Óptica/métodos , Fístula del Seno Cavernoso de la Carótida/diagnóstico , Estudios Transversales , Angiografía , Disco Óptico/irrigación sanguínea , Angiografía con Fluoresceína/métodos , Vasos RetinianosRESUMEN
Glioma is one of the most common primary malignancies of the central nervous system, which has aggressive clinical behavior and a poorer prognosis. MicroRNAs (miRs) are a class of small noncoding RNAs that function as mediators of gene expression, which can be sponged by circRNA provided with a closed circular structure. Dysregulations of circular RNAs (circRNAs) and miRs have been implicated in the development and progression of glioma. In the current study, we investigated the role of circular RNA hsa_circ_0076248 in mediating the oncogenesis of glioma by sponging miR-181a to modulate silent information regulator 1 (SIRT1) expression in vitro and in vivo. The quantitative real-time polymerase chain reaction results showed that the expression of miR-181a was significantly decreased in glioma tissues and cell lines compared with normal brain tissues and normal gliocyte, respectively, and the expression of hsa_circ_0076248 and SIRT1 demonstrated the opposite. Bioinformatics analysis identified hsa_circ_0076248 could sponge miR-181a, and miR-181a could target the mRNA of SIRT1. Our results verified that downregulating hsa_circ_0076248 or upregulating miR-181a could depress the proliferation and invasion of glioma in vitro and in vivo. The experiment also showed that downregulating hsa_circ_0076248 or upregulating miR-181a could remarkably promote the temozolomide chemotherapy sensitivity. Furthermore, Western blot analysis testified that downregulating hsa_circ_0076248 or upregulating miR-181a could promote the expression of p53 and SIRT1. In summary, our study sheds light on the regulatory mechanism of hsa_circ_0076248 in glioma growth and invasion via sponging miR-181a, which downregulates the SIRT1 expression and also suggests that hsa_circ_0076248, miR-181a, and SIRT1 may serve as potential therapeutic targets for glioma.
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Biomarcadores de Tumor/metabolismo , Neoplasias Encefálicas/patología , Regulación Neoplásica de la Expresión Génica , Glioblastoma/patología , MicroARNs/genética , ARN Circular/genética , Sirtuina 1/metabolismo , Animales , Apoptosis , Biomarcadores de Tumor/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Carcinogénesis , Estudios de Casos y Controles , Movimiento Celular , Proliferación Celular , Femenino , Glioblastoma/genética , Glioblastoma/metabolismo , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Invasividad Neoplásica , Pronóstico , Sirtuina 1/genética , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
OBJECTIVE: To explore the expressions of miR-26b and cyclooxygenase (COX)-2 in different grades of gliomas and the effect of miR-26b on glioma cell proliferation, invasion and migration.â© Methods: Western blot and Real-time quantitative PCR (qRT-PCR) were used to detect the expression levels of miR-26b and COX-2 in different grades of gliomas. Human glioma cells were transfected with miR-26b mimics. qRT-PCR was employed to detect the mRNA expressions of miR-26b and COX-2 after miR-26b mimics transfection, while dual-luciferase reporter assay was used to investigate the regulatory effect of miR-26b on COX-2. Cell counting kit-8 (CCK8), trans-well invasion assay and scratch assay were used to detect the proliferation, invasion and migration of human U87 glioma cells after miR-26b mimic transfection, respectively. The antitumor effect of miR-26b was verified by evaluating the volume and weight of tumor in nude mice.â© Results: With the increase in tumor grades, the expression of miR-26b was significantly decreased (P<0.05), while COX-2 expression was increased (P<0.001). Dual luciferase assay confirmed that miR-26b could directly regulate the protein expression of COX-2. MiR-26b mimics could significantly reduce the expression of COX-2 (P<0.05) and suppress the proliferation, invasion and migration of glioma cell (P<0.05). The volume and weight of tumor in MiR-26b mimics transfection group were smaller than those in the control group.â© Conclusion: Overexpression of miR-26b may inhibit proliferation, invasion, and migration of glioma by suppressing the expression of COX-2. Therefore, the miR-26b/COX-2 pathway might be a therapeutic target in glioma.
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Ciclooxigenasa 2/química , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/fisiología , Glioma/química , Glioma/fisiopatología , MicroARNs/química , MicroARNs/genética , MicroARNs/fisiología , Animales , Línea Celular Tumoral , Movimiento Celular/genética , Movimiento Celular/fisiología , Proliferación Celular/genética , Proliferación Celular/fisiología , Humanos , Ratones Desnudos , Clasificación del Tumor , Invasividad Neoplásica/genética , Invasividad Neoplásica/fisiopatología , Reacción en Cadena en Tiempo Real de la Polimerasa , TransfecciónRESUMEN
BACKGROUND: Neurite outgrowth is one of the important therapeutic strategies for neuronal plasticity and regeneration in neural disorders. Fasudil is a clinical medication that is used to treat subarachnoid haemorrhage (SAH) and that is beneficial for many animal models of central nervous system (CNS) diseases. In this study, we hypothesised that fasudil administration would promote neurite outgrowth in neural stem cells (NSCs). METHODS: Changes in cell morphology were imaged under a light microscope, and neurite-bearing cells were counted. Cell viability and the necrosis rate were determined by MTT and LDH assays, respectively. Additionally, western blot and immunofluorescence analyses were performed to detect protein expression levels. RESULTS: We found that fasudil promoted neurite outgrowth in C17.2 cells in a time- and dose-dependent manner. The neurite-bearing C17.2 cells were differentiated by detecting the changes in neural and astrocytic markers after fasudil treatment through down-regulating Notch signalling. Previously, fasudil was reported to induce autophagy, which plays an important role in neural differentiation. However, both rapamycin, an autophagy inducer, and 3-methyl-adenine (3-MA), an autophagy inhibitor, had no effects on the fasudil-induced neurite outgrowth, suggesting that autophagy may be not involved in this process. CONCLUSION: In summary, fasudil could stimulate neurite outgrowth and differentiation in C17.2 cells by modulating Notch signalling but not autophagy.
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1-(5-Isoquinolinesulfonil)-2-Metilpiperazina/análogos & derivados , Células-Madre Neurales/efectos de los fármacos , Neuritas/efectos de los fármacos , Neurogénesis/efectos de los fármacos , Receptores Notch/metabolismo , Vasodilatadores/farmacología , 1-(5-Isoquinolinesulfonil)-2-Metilpiperazina/farmacología , Animales , Autofagia/efectos de los fármacos , Bloqueadores de los Canales de Calcio/farmacología , Línea Celular , Ratones , Células-Madre Neurales/citología , Células-Madre Neurales/metabolismo , Neuritas/metabolismo , Neuritas/ultraestructura , Inhibidores de Proteínas Quinasas/farmacología , Transducción de Señal/efectos de los fármacosRESUMEN
Ischemic stroke is a significant burden on human health worldwide. Carotid Atherosclerosis stenosis plays an important role in the comprehensive assessment and prevention of ischemic stroke patients. High-resolution vessel wall magnetic resonance imaging has emerged as a successful technique for assessing carotid atherosclerosis stenosis. This advanced imaging modality has shown promise in effectively displaying a wide range of characteristics associated with the condition, leading to a comprehensive evaluation. High-resolution vessel wall magnetic resonance imaging not only enables a comprehensive evaluation of the instability of carotid atherosclerosis stenosis plaques but also provides valuable information for understanding the pathogenesis and predicting the prognosis of ischemic stroke patients. The purpose of this article is to review the application of high-resolution magnetic resonance imaging in ischemic stroke and carotid atherosclerotic stenosis.
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BACKGROUND AND PURPOSE: Intracranial atherosclerotic stenosis (ICAS) is a major cause of ischemic stroke, and high-resolution vessel wall imaging (HR-VWI) can be used to assess the plaque characteristics of ICAS. This study combined HR-VWI, hemodynamics, and peripheral blood inflammatory indicators to investigate the role of these factors in symptomatic intracranial atherosclerotic stenosis (sICAS) and their inter-relationships. METHODS: Patients diagnosed with atherosclerotic middle cerebral artery stenosis were recruited retrospectively from June 2018 to July 2022. Plaque enhancement was qualitatively and quantitatively analyzed, and the degree of plaque enhancement was graded according to the plaque-to-pituitary stalk contrast ratio (CR). Computational fluid dynamics models were constructed, and then hemodynamic parameters, including wall shear stress (WSS) and pressure ratio (PR), were measured and recorded. Univariate and multivariable analyses were performed to identify factors that can predict sICAS. In addition, the correlation analysis between the plaque characteristics on HR-VWI, hemodynamic parameters, and peripheral blood inflammatory indicators was performed to investigate the interrelationships between these factors. RESULTS: Thirty-two patients were included. A higher proportion of plaque enhancement, maximum WSS, and WSS ratio (WSSR) were significantly associated with sICAS. The multiple logistic regression analysis showed that only the WSSR was an independent risk factor for sICAS. The correlation analysis revealed that both the CR and plaque burden showed linear positive correlation with the WSSR (R = 0.411, P = 0.022; R = 0.474, P = 0.007, respectively), and showed linear negative correlation with the lymphocyte to monocyte ratio (R = 0.382, P = 0.031; R = 0.716, P < 0.001, respectively). CONCLUSIONS: The plaque enhancement and WSSR were significantly associated with sICAS, WSSR was an independent risk factor for sICAS. Plaque enhancement and plaque burden showed linear correlation with the WSSR and lymphocyte-to-monocyte ratio (LMR). Hemodynamics and inflammation combined to promote plaque progression.
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Trastornos Cerebrovasculares , Arteriosclerosis Intracraneal , Accidente Cerebrovascular Isquémico , Placa Aterosclerótica , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular Isquémico/complicaciones , Arteria Cerebral Media/diagnóstico por imagen , Estudios Retrospectivos , Constricción Patológica , Hemodinámica , Placa Aterosclerótica/complicaciones , Placa Aterosclerótica/diagnóstico por imagen , Arteriosclerosis Intracraneal/complicaciones , Arteriosclerosis Intracraneal/diagnóstico por imagen , Imagen por Resonancia Magnética/métodosRESUMEN
BACKGROUND AND PURPOSE: Intracranial atherosclerotic stenosis (ICAS) is a major cause of ischemic stroke (IS), and high-resolution vessel wall imaging (HR-VWI) can be used to assess the plaque characteristics of ICAS. This study aimed to qualitatively and quantitatively assess plaque enhancement of ICAS and to investigate the relationship between plaque enhancement, plaque morphological features, and IS. METHODS: Data from adult patients with ICAS from April 2018 to July 2022 were retrospectively collected, and all patients underwent HR-VWI examination. Plaque enhancement was qualitatively and quantitatively assessed, and the plaque-to-pituitary stalk contrast ratio (CR) indicated the degree of plaque enhancement. Plaque characteristics, such as plaque burden and area, were quantitatively measured using HR-VWI. Furthermore, receiver-operating characteristic (ROC) analysis was performed to assess the ability of CR to discriminate plaque enhancement. The patients were divided into a symptomatic ICAS group and an asymptomatic ICAS group according to the clinical and imaging characteristics. Univariate and multivariate analyses were performed to investigate which factors were significantly associated with plaque enhancement and symptomatic ICAS. The plaque burden and CR were compared using linear regression. RESULTS: A total of 91 patients with ICAS were enrolled in this study. ICAS plaque burden was significantly associated with plaque enhancement (p = .037), and plaque burden was linearly positively correlated with CR (R = 0.357, p = .001). ROC analysis showed that the cutoff value of CR for plaque enhancement was 0.56 (specificity of 81.8%). Both plaque enhancement and plaque burden were significantly associated with symptomatic ICAS, and only plaque enhancement was an independent risk factor after multivariate analysis. CONCLUSION: Plaque burden was an independent risk factor for plaque enhancement and showed a linear positive correlation with CR. The cutoff value of CR for plaque enhancement was 0.56, and CR ≥ 0.56 was significantly associated with symptomatic ICAS, which was independently associated with plaque enhancement.
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Arteriosclerosis Intracraneal , Placa Aterosclerótica , Accidente Cerebrovascular , Adulto , Humanos , Accidente Cerebrovascular/complicaciones , Constricción Patológica/complicaciones , Estudios Retrospectivos , Factores de Riesgo , Placa Aterosclerótica/diagnóstico por imagen , Arteriosclerosis Intracraneal/diagnóstico por imagen , Imagen por Resonancia Magnética/métodosRESUMEN
Background and purpose: Gadolinium enhancement on high-resolution vessel wall imaging (HR-VWI) is an imaging marker of intracranial atherosclerotic stenosis (ICAS) plaque instability. This study aimed to evaluate the relationships between hematological inflammatory indicators and the enhancement of ICAS plaques and to search for hematological indicators that can predict ICAS plaque instability. Methods: Consecutive adult patients diagnosed with ICAS from April 2018 to December 2021 were recruited retrospectively, and every patient underwent HR-VWI. Plaque enhancement was measured qualitatively and quantitatively. The plaque-to-pituitary stalk contrast ratio (CR) indicated the degree of plaque enhancement. Clinical and laboratory data, including the lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), and systemic immune inflammation index (SII), were recorded. The hematological inflammatory indicators were compared between ICAS patients with and without plaque enhancement and between patients with and without symptomatic plaque. The hematological inflammatory indicators and the CR were compared using linear regression. Furthermore, receiver operating characteristic curve analysis was performed to assess the discriminative abilities of the inflammatory indicators to predict plaque instability. Results: Fifty-nine patients were included. The NLR, SII and LMR were significantly correlated with plaque enhancement. The LMR was independently associated with plaque enhancement, and a linear negative correlation was observed between the LMR and CR (R = 0.716, P < 0.001). The NLR, LMR, plaque enhancement and CR were significantly associated with symptomatic ICAS, and the LMR and plaque enhancement were independent risk factors for symptomatic ICAS. The optimal cutoff value of the admission LMR to distinguish symptomatic plaque from asymptomatic plaque was 4.0 (80.0% sensitivity and 70.6% specificity). Conclusion: The LMR was independently associated with ICAS plaque enhancement and showed a linear negative correlation with CR. The LMR and plaque enhancement were independent risk factors for symptomatic ICAS. An LMR ≤ 4.0 may predict ICAS plaque instability.
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Arteriosclerosis Intracraneal , Placa Aterosclerótica , Adulto , Constricción Patológica , Medios de Contraste , Gadolinio , Humanos , Arteriosclerosis Intracraneal/complicaciones , Linfocitos , Monocitos , Estudios RetrospectivosRESUMEN
Background and Purpose: Neutrophil-lymphocyte ratio (NLR) predicts clinical outcomes in patients with stroke. Aneurysm wall enhancement (AWE) on high-resolution vessel wall magnetic resonance imaging (HR-VWI) is an inflammation marker for intracranial aneurysm (IA). This study aims to evaluate the association of NLR as a peripheral blood inflammatory marker with circumferential AWE in patients with IA. Methods: We analyzed data of consecutive patients harboring IAs between September 2017 and December 2021 at our institution. The peripheral blood inflammatory indicators were compared between patients with ruptured and unruptured IAs. The presence of circumferential AWE in unruptured IA was identified and quantitatively measured using the aneurysm-to-pituitary stalk contrast ratio (CRstalk) on HR-VWI. We used the optimal cutoff value of 0.5 for CRstalk to differentiate circumferential AWE in unruptured IAs. We assessed the relationship of clinical, laboratory, and radiological characteristics with circumferential AWE and CRstalk ≥0.5 in unruptured IAs. Results: The study group was composed of one hundred and twenty-five patients with 142 IAs. NLR level at admission was significantly higher in patients with ruptured IAs than those with unruptured IAs (7.55 vs. 1.81; P < 0.001). AWE on HR-VWI was present in 30 patients with unruptured IAs (38.5%), including 12 with focal AWE and 18 with circumferential AWE. NLR (odds ratio (OR), 2.168; 95% CI, 1.149-4.088) and size (odds ratio, 1.370; 95% CI, 1.126-1.667) were independently associated with circumferential AWE in unruptured IA. NLR was also independently associated with circumferential AWE in small unruptured IA (<7 mm). Furthermore, NLR level at admission was associated with CRstalk ≥.5 in patients with unruptured IA. The optimal cutoff value of NLR for circumferential AWE was 1.86. Conclusion: NLR is a valuable peripheral blood inflammatory marker is more often in the rupture status of IA and was associated with circumferential AWE on HR-VWI in unruptured IA.
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BACKGROUND: Aneurysm wall enhancement on high-resolution vessel wall imaging (HR-VWI) may represent vessel wall inflammation for unruptured intracranial aneurysms (UIAs). Further evidence for the role of circumferential aneurysm wall enhancement (CAWE) in evaluating the instability of UIAs is required, especially in small aneurysms (<7 mm). METHODS: We analyzed patients with saccular UIAs who prospectively underwent HR-VWI on a 3.0 T MRI scanner in our center from September 2017 to August 2021. The presence of AWE was identified and quantitatively measured using the aneurysm-to-pituitary stalk contrast ratio (CRstalk) with maximal signal intensity value. The PHASES and ELAPSS scores were used to assess the risk of aneurysm rupture and growth. We evaluated the association of CAWE and CRstalk value with intracranial aneurysm instability. RESULTS: One hundred patients with 109 saccular UIAs were included in this study. Eighty-three UIAs (76.1%) had a size smaller than 7 mm. PHASES and ELAPSS scores were significantly higher in UIAs with CAWE than in UIAs without CAWE (p < .01). The association of CAWE with PHASES and ELAPSS scores remained in small UIAs (<7 mm). The optimal cutoff value of CRstalk for CAWE was 0.5. PHASES and ELAPSS scores were significantly higher in UIAs with CRstalk ≥0.5 than in UIAs with CRstalk <0.5 (p < .01). CONCLUSIONS: CAWE on HR-VWI is a valuable imaging marker for aneurysm instability in UIAs. CRstalk value ≥0.5 may be associated with a higher risk of intracranial aneurysm rupture and growth.
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Aneurisma Roto , Aneurisma Intracraneal , Aneurisma Roto/diagnóstico por imagen , Humanos , Inflamación , Aneurisma Intracraneal/diagnóstico por imagen , Imagen por Resonancia Magnética/métodosRESUMEN
Glioma is the most common malignant tumor of the nervous system. Studies have shown the microRNA-26b (miR-26b)/cyclooxygenase-2 (COX-2) axis in the development and progression in many tumor cells. Our study aims to investigate the effect and mechanism of the miR-26b/COX-2 axis in glioma. Decreased expression of miR-26b with increased levels of COX-2 was found in glioma tissues compared with matched normal tissues. A strong negative correlation was observed between the level of miR-26b and COX-2 in 30 glioma tissues. The miR-26b was then overexpressed by transfecting a miR-26b mimic into U-373 cells. The invasive cell number and wound closing rate were reduced in U-373 cells transfected with miR-26b mimic. In addition, COX-2 siRNA enhanced the effect of miR-26b mimic in suppressing the expression of p-ERK1 and p-JNK. Finally, the in vivo experiment revealed that miR-26b mimic transfection strongly reduced the tumor growth, tumor volume, and expression of matrix metalloproteinase-2 (MMP-2) and MMP-9. Taken together, our research indicated a miR-26b/COX-2/ERK/JNK axis in regulating the motility of glioma in vitro and in vivo, providing a new sight for the treatment of glioma.
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Neoplasias Encefálicas/patología , Ciclooxigenasa 2/genética , Glioma/patología , MicroARNs/fisiología , Animales , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Ciclooxigenasa 2/análisis , Quinasas MAP Reguladas por Señal Extracelular/fisiología , Humanos , Proteínas Quinasas JNK Activadas por Mitógenos/fisiología , Sistema de Señalización de MAP Quinasas , Ratones , MicroARNs/análisis , Invasividad NeoplásicaRESUMEN
BACKGROUND: The development of heart failure after acute myocardial infarction (MI) was related to left ventricular (LV) pathological remodeling and dysfunction. Cardiac stem cells (CSCs) provided a new option to treat acute MI. This study was to investigate the effects of CSCs on structural and functional alteration in acute MI. METHODS: Acute MI was induced in 20 Sprague-Dawley rats by ligation of the left anterior descending coronary artery. Two weeks after MI, animals were randomized into CSCs or control group. LV geometry and function were echocardiographically measured at baseline, 2, 4, and 6 weeks after MI. After measuring hemodynamics at 6 weeks after MI, hearts were harvested for tracing CSCs stained by PKH26 and testing expression of VEGF-α/TGF-ß1 by RT-PCR and ELISA. RESULTS: Two weeks after MI, there were significant decreases in interventricular septal systolic and diastolic thickness (IVSTs/d), while increases in LV systolic and diastolic dimension (LVDs/d). Consequently, this contributed to decreases in ejection fraction (EF) and fractional shorting (FS). With the treatment of CSCs for 4 weeks, significant better ejection fraction (EF) and fractional shorting (FS) were achieved in CSCs group accompanied by the reduction in LV systole and diastole dimension (LVDs/d). Besides, a significant improvement in the maximal rate of LV pressure development and decline (peak +dP/dt and -dP/dt, respectively) was observed. Moreover, significantly higher VEGF-α was expressed in CSCs group rather than TGF-ß1. CONCLUSION: CSCs significantly prevented structural and functional deterioration after MI with increasing expression of VEGF-α.
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Infarto del Miocardio/cirugía , Miocardio , Trasplante de Células Madre , Células Madre , Disfunción Ventricular Izquierda/prevención & control , Función Ventricular Izquierda , Remodelación Ventricular , Animales , Células Cultivadas , Modelos Animales de Enfermedad , Masculino , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Infarto del Miocardio/fisiopatología , Miocardio/metabolismo , Miocardio/patología , Fenotipo , Ratas Sprague-Dawley , Regeneración , Células Madre/metabolismo , Volumen Sistólico , Factores de Tiempo , Factor de Crecimiento Transformador beta1/metabolismo , Trasplante Homólogo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Disfunción Ventricular Izquierda/metabolismo , Disfunción Ventricular Izquierda/patología , Disfunción Ventricular Izquierda/fisiopatología , Presión VentricularRESUMEN
BACKGROUND: The tumor microenvironment is partially characterized by a state of chronic inflammation, and radiologic features are related to the tumor's biological behavior. This study was conducted to explore whether peripheral blood inflammatory markers combined with radiologic features could predict proliferation potency. METHODS: This study retrospectively reviewed 183 patients with a primary diagnosis of glioma. Clinical characteristics, preoperative peripheral full blood count data, and brain magnetic resonance imaging findings were reviewed to analyze the expression of inflammatory markers neutrophil lymphocyte ratio (NLR), monocyte lymphocyte ratio, and platelet lymphocyte ratio (PLR), as well as radiologic features such as location, peritumor edema, and contrast enhancement. Immunohistochemical staining was performed to determine the proliferation index (i.e., expression of Ki-67). Receiver operating characteristic curves for cutoff value, various bivariate tests, and binary logistic regression analyses were applied. RESULTS: Proliferation index was highly associated with tumor grade, showing a gradually increasing tendency. A Ki-67 cutoff value >9% predicted high-grade glioma (HGG). Mean NLR and PLR were significantly higher in the HGG group compared with the low-grade glioma group (NLR: 3.11 ± 0.59 vs. 4.27 ± 1.13; PLR: 133.07 ± 13.17 vs. 161.51 ± 38.99; P < 0.01 for both). Contrast enhancement was more likely in the HGG group, but there was no significant between-group difference in peritumor edema. Logistic regression analysis identified the following risk factors for prediction of proliferation potency: age, Karnofsky Performance Score, NLR, PLR, and contrast enhancement. However, age >43 years, NLR >3.68, and positive contrast enhancement independently predicted a higher proliferation rate. CONCLUSIONS: NLR and contrast enhancement were positively correlated with the proliferation potency of gliomas.
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Biomarcadores de Tumor/sangre , Neoplasias Encefálicas/diagnóstico por imagen , Proliferación Celular/fisiología , Glioma/sangre , Glioma/diagnóstico por imagen , Mediadores de Inflamación/sangre , Adulto , Estudios de Cohortes , Femenino , Humanos , Linfocitos/metabolismo , Masculino , Persona de Mediana Edad , Neutrófilos/metabolismo , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Microambiente Tumoral/fisiología , Adulto JovenRESUMEN
PURPOSE: Numerous studies have reported that glioma patients with isocitrate dehydrogenase 1(IDH1) R132H mutation are sensitive to temozolomide treatment. However, the mechanism of IDH1 mutations on the chemosensitivity of glioma remains unclear. In this study, we investigated the role and the potential mechanism of Nrf2 in IDH1 R132H-mediated drug resistance. METHODS: Wild type IDH1 (R132H-WT) and mutant IDH1 (R132H) plasmids were constructed. Stable U87 cells and U251 cells overexpressing IDH1 were generated. Phenotypic differences between IDH1-WT and IDH1 R132H overexpressing cells were evaluated using MTT, cell colony formation assay, scratch test assay and flow cytometry. Expression of IDH1 and its associated targets, nuclear factor-erythroid 2-related factor 2 (Nrf2), NAD(P)H quinine oxidoreductase 1 (NQO1), multidrug resistant protein 1 (MRP1) and p53 were analyzed. RESULTS: The IDH1 R132H overexpressing cells were more sensitive to temozolomide than WT and the control, and Nrf2 was significantly decreased in IDH1 R132H overexpressing cells. We found that knocking down Nrf2 could decrease resistance to temozolomide. The nuclear translocation of Nrf2 in IDH1 R132H overexpressing cells was lower than the WT and the control groups after temozolomide treatment. When compared with WT cells, NQO1 expression was reduced in IDH1 R132H cells, especially after temozolomide treatment. P53 was involved in the resistance mechanism of temozolomide mediated by Nrf2 and NQO1. CONCLUSIONS: Nrf2 played an important role in IDH1 R132H-mediated drug resistance. The present study provides new insight for glioma chemotherapy with temozolomide.
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Antineoplásicos Alquilantes/farmacología , Neoplasias Encefálicas/tratamiento farmacológico , Dacarbazina/análogos & derivados , Glioma/tratamiento farmacológico , Isocitrato Deshidrogenasa/genética , Mutación/genética , Factor 2 Relacionado con NF-E2/metabolismo , Neoplasias Encefálicas/genética , Línea Celular Tumoral , Dacarbazina/farmacología , Resistencia a Antineoplásicos , Regulación Neoplásica de la Expresión Génica , Glioma/genética , Humanos , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , NAD(P)H Deshidrogenasa (Quinona)/genética , NAD(P)H Deshidrogenasa (Quinona)/metabolismo , Factor 2 Relacionado con NF-E2/genética , Transducción de Señal , Temozolomida , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
OBJECTIVE: There is currently no consensus on a standardized treatment strategy for olfactory neuroblastoma (ONB), especially for intracranial invasion. This purpose of this study is to explore the appropriate treatment modality and prognostic factors of intracranial invasive ONB. STUDY DESIGN: Case series with chart review. SETTING: The study was conducted at the Sun Yat-sen Memorial Hospital and the Cancer Center of Sun Yat-sen University, China. SUBJECTS AND METHODS: Twenty-five cases of intracranial invasive ONB were collected and investigated using a retrospective review analysis from patients diagnosed between 1980 and 2005. RESULTS: The 1-, 3-, and 5-year overall survival rates for the group were 55%, 46%, and 31%, respectively. The subgroups who did not receive surgical treatment had worse survival rates than those who did receive treatment. In particular, patients who did not receive any therapy did not live past 1 year. In contrast, the group of patients treated by intranasal resection in combination with radiotherapy and/or chemotherapy showed a slightly better survival rate. It is important to note that the group of patients treated by craniofacial surgery combined with radiotherapy and/or chemotherapy had a markedly favorable prognosis, with 1-, 3-, and 5-year overall survival rates of up to 100%, 88%, and 66%, respectively. CONCLUSIONS: Craniofacial surgery in combination with radiotherapy and/or chemotherapy was an effective treatment for intracranial invasive ONB. In addition, it was found that age may not be an important prognostic factor for intracranial invasive ONB; however, the rate of intracalvarial invasion was found to be a potent marker for predicting the prognosis of patients.
Asunto(s)
Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/terapia , Estesioneuroblastoma Olfatorio/terapia , Cavidad Nasal , Neoplasias Nasales/terapia , Adolescente , Adulto , Neoplasias Encefálicas/mortalidad , Quimioterapia Adyuvante , Niño , China , Estudios de Cohortes , Terapia Combinada , Supervivencia sin Enfermedad , Estesioneuroblastoma Olfatorio/mortalidad , Estesioneuroblastoma Olfatorio/secundario , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica/patología , Estadificación de Neoplasias , Procedimientos Neuroquirúrgicos/métodos , Neoplasias Nasales/mortalidad , Neoplasias Nasales/patología , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Análisis de Supervivencia , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND & OBJECTIVE: Brain gliomas seldom undergo extracranial metastasis. Local recurrence is the main reason of tumor patient's death. Therefore, it is important to detect tumor biological features through determination of gene expression. This study was designed to investigate the expression of nm23 (non-metastasis gene, nm23)and PCNA (proliferating cell nuclear antigen) and evaluate the malignancy, recurrence, and prognosis of the tumor. METHODS: In 50 specimens of different malignant gliomas,the expression of nm23 and PCNA were examined using SP immunohistochemical staining. RESULTS: (1)The label indexes of nm23 and PCNA in low-grade gliomas were 3.40+/-0.27 and 3.60+/-0.05, respectively; while the label indexes of nm23 and PCNA in high-grade gliomas were 1.72+/-0.18 and 6.20+/-0.23, respectively.There was significant difference between the two groups(P< 0.05). (2)The positive rates of nm23 and PCNA were 56% (14 cases) and 64% (16 cases) in 25 cases of low-grade gliomas, while the positive rates of nm23 and PCNA were 12% (3 cases) and 88% (22 cases) in 25 cases of high-grade gliomas. There was significant difference between the two groups (P< 0.05). (3)The positive rates of nm23 and PCNA were 0% (0 cases) and 100% (9 cases) in 9 cases of recurrent gliomas, while the positive rates of nm23 and PCNA were 50%(34 cases) and 50%(4 cases) in 8 cases of non-recurrent gliomas. There was significant difference between the two groups (P< 0.05). (4)The label indexes of nm23 and PCNA in gliomas were inversely correlated (r=-0.5335,P< 0.001). CONCLUSION: (1)The expression of nm23 is inversely correlated with the malignancy of gliomas,i.e.the lower expression indicates the higher malignancy. (2)The expression of PCNA is associated with the increased malignancy. (3)Both nm23 and PCNA may be useful biological markers to evaluate the malignancy and prognosis of patients with gliomas.