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Objective: The measurement of the right and left axillary arteries and aortic arch and their vessels by multi-row spiral CT angiography provides the basis for clinical catheter selection and depth for axillary artery placement. This study reported the clinical experience of 7 patients who successfully underwent ultrasound-guided percutaneous axillary artery cannulation for veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Methods: Patients who had CT angiography of the thoracic aorta at our institution between January 2020 and March 2022 were assessed for eligibility and included. The diameters of the cephalic trunk (D1), right common carotid artery (D2), right axillary artery (D3), left common carotid artery (D4), left axillary artery opening (D5), right axillary artery cannulation length (L1), and left axillary artery cannulation length (L2) were measured. The tangential angles α, ß, and γ of the cephalic trunk, left common carotid artery and left subclavian and aorta was measured using an automatic angle-forming tool. The decision to use a 15F cannula for ultrasound-guided percutaneous axillary artery cannulation in veno-arterial extracorporeal membrane oxygenation (VA-ECMO) aims to achieve optimal vascular access. This cannula size strikes a balance, providing sufficient blood flow rates for ECMO support while minimizing the risk of complications associated with larger cannulas. Precise measurements of arterial dimensions, including the cephalic trunk, common carotid arteries, and axillary arteries, play a crucial role in guiding catheter selection and determining the depth of axillary artery placement. These measurements allow for tailored approaches based on individual patient characteristics, enhancing the safety and efficacy of the intervention. Additionally, measuring tangential angles (α, ß, and γ) provides insights into arterial alignment, optimizing the cannula trajectory for efficient blood flow. The use of an automatic angle-forming tool enhances measurement precision, contributing to procedural accuracy, minimizing complications, and ensuring the success of ultrasound-guided percutaneous axillary artery cannulation. In summary, the choice of a 15F cannula and precise measurements are essential components of the methodology, emphasizing safety, efficacy, and personalized approaches in VA-ECMO. From March to June 2022, 7 patients (6 males and 1 female) in our intensive care medicine department underwent successful ultrasound-guided percutaneous axillary artery cannulation for VA-ECMO with 15F cannula, including 3 cases with extracorporeal cardiopulmonary resuscitation (ECPR) and 4 cases with circulatory collapse. Results: 292 patients met the study criteria, 215 males and 77 females, with a mean age of 67.2±14.2 years. The measurements showed that D1 was (13.1±2.0) mm, D2 was (8.8±2.5) mm, D3 was (6.1±1.2) mm, D4 was (8.3±3.5) mm, D5 was (6.1±1.1) mm, L1 was (114.1±17.8) mm, and L2 was (128.4±20.2) mm. The tangential angles α of the cephalic trunk left common carotid artery and left subclavian artery to the aorta were (43.8°±17.1°), ß was (50.7°±14.8°), and γ was (62.4°±19.1°). Males had significantly wider D3 and D5, longer L1 and L2, and smaller gamma angles than females (P < .05). Three ECPR cases showed no recovery of the spontaneous heartbeat with femoral artery cannulation for VA-ECMO but recovered spontaneous heartbeat after axillary artery cannulation for VA-ECMO was adopted. The measurements in this study have important implications for veno-arterial extracorporeal membrane oxygenation (VA-ECMO) procedures. They provide crucial information about arterial dimensions, including the cephalic trunk, common carotid arteries, and axillary arteries. This information guides clinicians in selecting catheters and determining the ideal depth for percutaneous axillary artery cannulation during ECMO interventions. Notable gender differences in arterial dimensions highlight the need for personalized approaches in ECMO procedures. Customizing catheter choices and cannulation depth based on individual patient characteristics, informed by these measurements, improves the safety and effectiveness of the intervention. The measured tangential angles (α, ß, and γ) offer insights into arterial alignment, crucial for optimizing cannula trajectory and ensuring proper alignment for efficient blood flow. The use of an automatic angle-forming tool enhances measurement precision, contributing to procedural accuracy and minimizing the risk of complications during ECMO procedures. In summary, these measurements directly enhance the precision and safety of VA-ECMO procedures, underscoring the importance of personalized approaches based on individual anatomical variations and improving overall intervention success and outcomes. Conclusion: Ultrasound-guided percutaneous axillary artery cannulation for VA-ECMO with a 15F cannula is clinically feasible. Axillary artery cannulation for VA-ECMO contributes to the restoration of spontaneous heartbeat in ECPR patients more than femoral artery cannulation, and the possible mechanism is a better improvement of coronary blood flow. However, the study has limitations, including a modest sample size and a single-center, retrospective design, impacting its generalizability. To validate and extend these findings, further research with larger and diverse cohorts, including prospective investigations, is necessary to ensure their applicability across various clinical settings and patient demographics in VA-ECMO.
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OBJECTIVE: To observe the protective effects of safflor Injection (SI) and extract of Ginkgo biloba (EGB) on lung ischemia-reperfusion injury (LIRI) and investigate its mechanism. METHODS: In vivo rabbit model of LIRI was reconstructed. Forty rabbits were randomly and equally divided into four groups: sham-operation group (sham group), ischemia-reperfusion group (model group), ischemia-reperfusion plus SI group (safflor group) and ischemia-reperfusion plus EGB injection group (EGB group). Malondialdehyde (MDA) content, superoxide dismutase (SOD) and xanthine oxidase (XO) activity in serum were measured. The wet/dry weight ratio (W/D) of the lung tissue and activity of myeloperoxidase (MPO) were also tested. Ultrastructure change of the lung tissue was observed by the electron microscope. The expression of intercellular adhesion molecule-1 (ICAM-1) was measured by immunohistochemistry (IHC). RESULTS: In the model group, MDA and XO increased and SOD decreased in serum compared with the sham group (P<0.01). The values of W/D, MPO and ICAM-1 of the model group were higher than those of the sham group (P<0.01), but those of the safflor group and EGB group were significantly lower than those of the model group (P<0.01). The IHC demonstrated that ICAM-1 expression in lung tissue of the model group was significantly higher than those of the safflor group (P<0.01). Compared with safflor group, in the EGB group MDA, XO, MPO decreased, SOD and ICAM-1 expression increased (P<0.05), but the change of W/D was not statistically significant (P>0.05). CONCLUSIONS: SI and EGB may attenuate LIRI through antioxidation, inhibition of neutrophil aggregation and down-regulation of ICAM-1 expression. But EGB had more effect on the antioxidation, while SI did better on regulating ICAM-1 expression.
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Ginkgo biloba/química , Pulmón/irrigación sanguínea , Extractos Vegetales/uso terapéutico , Sustancias Protectoras/uso terapéutico , Daño por Reperfusión/tratamiento farmacológico , Aceite de Cártamo/uso terapéutico , Animales , Femenino , Inmunohistoquímica , Inyecciones , Molécula 1 de Adhesión Intercelular/metabolismo , Pulmón/patología , Masculino , Malondialdehído/metabolismo , Extractos Vegetales/administración & dosificación , Extractos Vegetales/farmacología , Sustancias Protectoras/administración & dosificación , Sustancias Protectoras/farmacología , Conejos , Daño por Reperfusión/sangre , Aceite de Cártamo/administración & dosificación , Aceite de Cártamo/farmacología , Superóxido Dismutasa/sangre , Xantina Oxidasa/sangreRESUMEN
To investigate the effect of serum leptin level and leptin receptor (Lepr) genetic mutation on chronic bronchitis, we measured the serum leptin levels of 236 patients with chronic bronchitis and 107 healthy controls by ELISA, the genotype distribution of Lepr gene containing Gln223Arg polymorphic sites by the polymerase chain reaction-restriction fragment length polymorphism (RFLP) method, the levels of inflammatory markers in serum, and the concentration of neutrophils. We found that the GG genotype distribution and G gene frequency of Lepr gene Gln223Arg site of the patient group were higher than that in the control group. The serum high-sensitivity C-reactive protein and neutrophil granulocyte levels of the patient group were higher than those of the control group. But the leptin concentrations of those with GG genotype were lower than those with AA+AG genotype (P < .05). The mutation of Lepr gene Gln223Arg site may not directly influence the leptin level but could possibly advance the disease through inhibiting the biological effect of leptin.
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Bronquitis Crónica/genética , Polimorfismo Genético/genética , Receptores de Leptina/genética , Anciano , Bronquitis Crónica/sangre , Estudios de Casos y Controles , Femenino , Humanos , Leptina/sangre , Masculino , Persona de Mediana EdadRESUMEN
Deficiency of the programmed cell death-1 (PD-1) gene enhances T-cell activation and increases inflammation levels. It has been reported that atrial fibrillation (AF) is closely related to inflammation. The aim of the present study was to investigate the role of PD-1 deficiency in the pathogenesis of AF. Two groups of mice were used in our experiment: the C57BL/6 and the C57BL/6-PD-(1-/-) group. The expression of the inflammatory cytokines interleukin (IL)-2, -4, -6, -10, -17, interferon-γ and tumor necrosis factor were detected. Furthermore, the levels of atrial myocyte oxidative stress, the atrial effective refractory period (AERP) and the atrial myocardial fibrosis levels were determined. Compared with the C57BL/6 group, we found that the inflammatory cytokines were significantly increased in the PD-1(-/-) group and the levels of atrial myocyte oxidative stress in the PD-1(-/-) group were also higher. The AERP became shorter and the dispersion of AERP was increased in the PD-1(-/-) group. Moreover, the PD-1(-/-) group presented significant atrial myocardial fibrosis but the C57BL/6 group did not. Our findings strongly suggest that the higher levels of inflammatory cytokines and atrial myocyte oxidative stress were present in the PD-1(-/-) mice and resulted in atrial electricity and structural remodeling. Due to the atrial remodeling, the PD-1(-/-) mice were more likely to develop AF.
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Fibrilación Atrial/genética , Fibrilación Atrial/patología , Atrios Cardíacos/patología , Receptor de Muerte Celular Programada 1/genética , Animales , Fibrilación Atrial/inmunología , Fibrilación Atrial/fisiopatología , Muerte Celular , Eliminación de Gen , Atrios Cardíacos/inmunología , Atrios Cardíacos/metabolismo , Atrios Cardíacos/fisiopatología , Interferón gamma/inmunología , Interleucinas/inmunología , Masculino , Ratones , Ratones Endogámicos C57BL , Estrés Oxidativo , Periodo Refractario Electrofisiológico , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
SOX9 belongs to the SOX (Sry-related high-mobility group box) family and acts as a transcription factor that plays a central role in the development and differentiation of multiple cell lineages. Recent studies have demonstrated that SOX9 is required for the carcinogenesis in several cancer types. The aim of this study was to investigate the clinicopathological significance of SOX9 expression in human malignant glioma. SOX9 mRNA expression was detected by real-time quantitative RT-PCR assay in glioma and nonneoplastic brain tissues. Then, the association of SOX9 mRNA expression with clinicopathological factors or prognosis of glioma patients was statistically analyzed. In addition, the small interfering RNA was used to knockdown SOX9 expression in a glioma cell line and to analyze the effects of SOX9 inhibition on cell growth, cell cycle and apoptosis of glioma cell line. The expression level of SOX9 mRNA in glioma tissues was significantly higher than that in corresponding nonneoplastic brain tissues (P < 0.001). In addition, a high level of SOX9 mRNA expression was significantly more common in glioma tissues with advanced WHO grade than those with low grade (P = 0.02). The increased expression of SOX9 mRNA was also significantly correlated with low Karnofsky performance score (P = 0.008). Meanwhile, the disease-free and overall survival rates of patients with high SOX9 mRNA expression were obviously lower than those of patients with low SOX9 mRNA expression (both P = 0.01). Multivariate analysis showed that high SOX9 mRNA expression was an independent prognostic factor for glioma patients (P = 0.02). Moreover, the down-regulation of SOX9 could inhibit the cell growth, induce the cell arrest in G2/M phase of cell cycle and enhance the apoptosis in glioma cells. Our data suggest for the first time that the over-expression of SOX9 mRNA is closely associated with poor clinical outcome of patients with malignant gliomas, and targeting SOX9 may be a novel therapeutic strategy for this tumor.
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Biomarcadores de Tumor/análisis , Neoplasias Encefálicas/metabolismo , Glioma/metabolismo , Factor de Transcripción SOX9/biosíntesis , Adulto , Apoptosis/fisiología , Western Blotting , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Proliferación Celular , Supervivencia sin Enfermedad , Femenino , Glioma/mortalidad , Glioma/patología , Humanos , Estimación de Kaplan-Meier , Masculino , Clasificación del Tumor , Pronóstico , Interferencia de ARN , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor de Transcripción SOX9/análisis , TransfecciónRESUMEN
PURPOSE: The activation of hedgehog (Hh) pathways has been studied extensively in many malignant tumors to elucidate their clinical diagnostic and prognostic utilities. However, their roles in primary gallbladder carcinoma (GBC) remain poorly understood. This study was conducted to clarify the immunoreactivity and prognostic value of Hh pathway components in GBC. METHODS: Levels of sonic hedgehog (Shh), its receptor, Patched (Ptch1), and its downstream transcription factor, Gli1 protein, were measured by immunohistochemistry in 93 specimens from patients with GBC. We analyzed the correlations between the expression of these factors and clinicopathological features, including prognosis. RESULTS: Among the 93 GBC specimens, 76 (81.7%), 70 (75.3%) and 66 (70.0%) were positive for Shh, Ptch1 and Gli1 expression, respectively. Expressions were significantly correlated with stage, lymph node metastasis, venous invasion, hepatic infiltration and lymphatic invasion (all P < 0.05). Patients with positive staining for Shh, Ptch1 and Gli1 had significantly lower survival rates than patients with negative staining. The expression patterns of Shh, Ptch1 and Gli1 were all associated with a malignant behavior risk category in GBC. CONCLUSIONS: To our knowledge, this is the first report to define the role of the Hh pathway in GBC. Shh, Ptch1 and Gli1 are frequently expressed in GBC and associated with poorer survival. Thus, high expressions of Shh, Ptch1 and Gli1 proteins could serve as auxiliary parameters for predicting the malignant behavior of GBC.
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Biomarcadores de Tumor/metabolismo , Neoplasias de la Vesícula Biliar/metabolismo , Proteínas Hedgehog/metabolismo , Receptores de Superficie Celular/metabolismo , Factores de Transcripción/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Neoplasias de la Vesícula Biliar/mortalidad , Neoplasias de la Vesícula Biliar/patología , Neoplasias de la Vesícula Biliar/cirugía , Humanos , Inmunohistoquímica , Metástasis Linfática , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Receptores Patched , Receptor Patched-1 , Pronóstico , Análisis de Supervivencia , Proteína con Dedos de Zinc GLI1RESUMEN
OBJECTIVE: Human neural precursor cell-expressed developmentally down-regulated 4 like (Nedd4L), a ubiquitin protein ligase, is expressed by various cancer cells and might have an oncogenic property. Its expression pattern in glioma tissues is unknown. Therefore, the aim of this study was to investigate whether Nedd4L is present in glioma and to evaluate the correlation of Nedd4L expression with the progression and prognosis of the disease. METHODS: Immunohistochemistry and western blot were used to investigate the expression of Nedd4L protein in 128 patients with gliomas. RESULTS: Immunohistochemistry showed a strong-to-weak range of Nedd4L staining with increasing pathologic grade of glioma (P < 0.001), which was in line with the results from western blot analysis. In addition, a non-parametric analysis revealed that the attenuated Nedd4L expression was significantly correlated with a large tumor diameter (P = 0.02), low Karnofsky performance score (P = 0.008), frequent intra-tumor necrosis (P = 0.01) and worse overall survival (P = 0.009). Furthermore, multivariate analysis showed that Nedd4L expression (P = 0.02) and intra-tumor necrosis (P = 0.03) were two important independent prognostic factors identified by the Cox proportional hazards model. CONCLUSIONS: Our results provide convincing evidence for the first time that the expression of Nedd4L is down-regulated in human gliomas. The glioma patients with lower Nedd4L expression have a worse prognosis.
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Biomarcadores de Tumor/análisis , Neoplasias Encefálicas/metabolismo , Complejos de Clasificación Endosomal Requeridos para el Transporte/biosíntesis , Glioma/metabolismo , Ubiquitina-Proteína Ligasas/biosíntesis , Adolescente , Adulto , Anciano , Western Blotting , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/patología , Niño , Regulación hacia Abajo , Femenino , Glioma/mortalidad , Glioma/patología , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Ubiquitina-Proteína Ligasas Nedd4 , Clasificación del Tumor , Pronóstico , Modelos de Riesgos Proporcionales , Adulto JovenRESUMEN
AIM: Excessive production of inflammatory mediators during invasive infection plays a key role in the pathogenesis of sepsis. In an attempt to improve survival of patients with this lethal syndrome, agents were developed to selectively inhibit mediators in this inflammatory response. Ulinastatin (UTI), a human protease inhibitor, inhibits the enhanced production of pro-inflammatory molecules. However, it is unknown if Ulinastatin treatment could result in protective effects for sepsis. The aim of this study was to investigate the role of Ulinastatin on septic rats. METHODS: Sixty male Wistar rats were divided into six groups, 10 of each: sham-operation plus PBS (5 ml), cecal ligation and puncture (CLP) plus PBS (5 ml), CLP plus UTI (5000 U/kg), CLP plus UTI (10,000 U/kg), CLP plus UTI (20,000 U/kg) and sham-operation plus UTI (10,000 U/kg). Rats in the UTI groups after CLP operation were treated with Ulinastatin by intraperitoneal injection at different doses and then compared with untreated sepsis control animals. RESULTS: The intestinal concentrations of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), and interleukin-13 (IL-13) were significantly higher in septic rats than those in normal rats. Ulinastatin administration effectively suppressed the levels of TNF-α and IL-6, whereas it markedly enhanced the levels of IL-10 and IL-13. CONCLUSION: Ulinastatin may possess a protective role in the septic process by inhibiting TNF-α and IL-6, and augmenting IL-10 and IL-13 concentrations in intestine of septic rats.
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Antiinflamatorios/farmacología , Glicoproteínas/farmacología , Sepsis/prevención & control , Inhibidores de Tripsina/farmacología , Animales , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Interleucina-1/biosíntesis , Interleucina-10/biosíntesis , Interleucina-6/biosíntesis , Masculino , Ratas , Ratas Wistar , Sepsis/inmunología , Factor de Necrosis Tumoral alfa/biosíntesisRESUMEN
A disintegrin and metalloprotease 8 (ADAM8) has been shown to be expressed in various cancer types, and its expression was associated with advanced progression of several tumors. However, little is known about ADAM8 in human gliomas. Therefore, we here evaluated the correlation of ADAM8 expression with the clinicopathological features and prognosis in the patients with gliomas. Immunohistochemistry and western blot were used to investigate the expression of ADAM8 protein, respectively, in 128 patients with gliomas. The expression levels of ADAM8 in glioma tissues were significantly higher (P = 0.002) than those in non-neoplastic brain tissues according to the immunohistochemistry analysis. In addition, a high level of ADAM8 expression was significantly more common in glioma tissues with advanced grade than those with low grade (P = 0.01), which were in line with the results of western blot analysis (P = 0.01). Moreover, the increased expression of ADAM8 was significantly correlated with low Karnofsky performance score (KPS) (P = 0.008), frequent intra-tumor necrosis (P = 0.01), and poor overall survival (P = 0.008). Furthermore, multivariate analysis identified the expression levels of ADAM8 (P = 0.01) and intra-tumor necrosis (P = 0.03) to be independent prognostic factors. These findings suggest for the first time that ADAM8 is frequently overexpressed in human gliomas and is closely associated with poor clinical outcome.
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Proteínas ADAM/biosíntesis , Biomarcadores de Tumor/análisis , Neoplasias Encefálicas/metabolismo , Glioma/metabolismo , Proteínas de la Membrana/biosíntesis , Proteínas ADAM/análisis , Adulto , Western Blotting , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/patología , Progresión de la Enfermedad , Femenino , Glioma/mortalidad , Glioma/patología , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Masculino , Proteínas de la Membrana/análisis , Clasificación del Tumor , Pronóstico , Modelos de Riesgos Proporcionales , Regulación hacia ArribaRESUMEN
OBJECTIVE: Matrix metalloprotease-1 and protease-activated receptor-1 axis plays an important role in many cancers, with activation often associated with poor survival. The aim of the present study was to determine whether the immunohistochemical detection of matrix metalloprotease-1 and protease-activated receptor-1 could provide useful information as novel therapeutic or prognostic factors in primary gallbladder carcinoma. METHODS: Eighty-six gallbladder carcinoma tissues were evaluated by immunohistochemistry for matrix metalloprotease-1 and protease-activated receptor-1 expressions. The association of matrix metalloprotease-1 and protease-activated receptor-1 expressions with clinicopathological characteristics and the univariate survival analysis for the influence of matrix metalloprotease-1 and protease-activated receptor-1 expressions on the overall survival were analyzed. RESULTS: Matrix metalloprotease-1 and protease-activated receptor-1 immunoreactivities were observed in 62 (72.1%) and 59 (68.6%) of the 86 gallbladder carcinoma cases, respectively. The tumors with the positive expressions of matrix metalloprotease-1 (P= 0.007) and protease-activated receptor-1 (P= 0.01) more frequently showed lymph node metastasis, respectively. In addition, the tumors with the positive expressions of matrix metalloprotease-1 and protease-activated receptor-1 tended to show a deeper invasion depth (P= 0.006 and 0.008, respectively) and more frequent lymphovascular invasion (both P= 0.01). The Kaplan-Meier survival curves demonstrated that patients with the positive expressions of matrix metalloprotease-1 and protease-activated receptor-1 had a significantly shorter survival time than those patients with their negative expression (both P= 0.02). CONCLUSIONS: A subset of gallbladder carcinoma cases revealed the overexpression of matrix metalloprotease-1 and protease-activated receptor-1, which was associated with a progressive pathological feature and an aggressive clinical course. Therefore, matrix metalloprotease-1 and protease-activated receptor-1 expressions may be predictors for a poor prognosis in patients with gallbladder carcinoma. This is the first report describing about the involvement of matrix metalloprotease-1 and protease-activated receptor-1 axis in gallbladder carcinoma.
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Biomarcadores de Tumor/metabolismo , Carcinoma/metabolismo , Carcinoma/patología , Neoplasias de la Vesícula Biliar/metabolismo , Neoplasias de la Vesícula Biliar/patología , Metaloproteinasa 1 de la Matriz/metabolismo , Receptor PAR-1/metabolismo , Análisis de Varianza , Carcinoma/enzimología , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Neoplasias de la Vesícula Biliar/enzimología , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Invasividad Neoplásica , PronósticoRESUMEN
JAK/STAT pathway transmits signals from the cell membrane to the nucleus in response to extracellular growth factors and cytokines. Activation of this pathway has been found in certain types of human tumors. The goal of this study was to investigate the correlation between the JAK/STAT pathway in human gliomas and patients' prognosis, which currently is unknown. Western blotting analysis and immunohistochemical staining were performed to detect JAK-1, phosphorylated JAK-1, and STAT-3 expression patterns in the biopsies from 96 patients with primary gliomas. Kaplan-Meier survival and Cox regression analyses were performed to evaluate the prognosis of patients. Western blotting analysis and immunohistochemical staining both indicated that the expression levels of JAK-1, phosphorylated JAK-1, and STAT-3 in primary glioma tissues were significantly higher than those in normal brain tissues (P < 0.001). Especially, the positive expression rates of JAK-1, phosphorylated JAK-1, and STAT-3 were significantly higher in patients with higher grade (P = 0.001, 0.001, and 0.002, respectively) and lower KPS score (P = 0.01, 0.008, and 0.01, respectively). Statistical analysis showed that patients with gliomas expressing JAK-1 and STAT-3 have lower overall survival rates relative to those not expressing these proteins. Cox multi-factor analysis showed that KPS (P = 0.03), WHO grade (P = 0.008), JAK-1 (P = 0.005), and STAT-3 (P = 0.006) were independent prognosis factors for human gliomas. These results provide convincing evidence for the first time that the JAK/STAT pathway may play a role in the progression of human gliomas. Its activated state might be a potent tool for predicting the clinical prognosis of patients with glioma.
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Neoplasias Encefálicas/metabolismo , Glioma/metabolismo , Janus Quinasa 1/metabolismo , Factor de Transcripción STAT1/metabolismo , Transducción de Señal , Western Blotting , Neoplasias Encefálicas/cirugía , Femenino , Estudios de Seguimiento , Glioma/cirugía , Humanos , Técnicas para Inmunoenzimas , Masculino , Persona de Mediana Edad , Pronóstico , Tasa de SupervivenciaRESUMEN
OBJECTIVE: Neuroepithelial-transforming protein 1 is a member of the guanine nucleotide exchange factor family, a group of proteins which are known to activate and thereby regulate Rho family members. Deregulation of neuroepithelial-transforming protein 1 expression has been found in certain types of human tumors. To investigate its prognostic value in human gliomas, which is currently unknown, we examined the correlation between neuroepithelial-transforming protein 1 expression and prognosis in patients with gliomas. METHODS: Immunohistochemical staining was performed to detect neuroepithelial-transforming protein 1 expression patterns in the biopsies from 96 patients with primary gliomas. Kaplan-Meier survival and Cox's regression analyses were performed to evaluate the prognosis of patients. RESULTS: Immunohistochemical analysis with anti-neuroepithelial-transforming protein 1 antibody revealed that neuroepithelial-transforming protein 1 was significantly associated with the Karnofsky performance scale score and World Health Organization grades of patients with gliomas. Especially, the positive expression rates of neuroepithelial-transforming protein 1 were significantly higher in patients with higher grade (P = 0.001) and lower Karnofsky's performance scale score (P = 0.005). The median survival of patients with high neuroepithelial-transforming protein 1 expression was significantly shorter than that with low expression and without expression (316, 892 and 1180 days, respectively). Cox's multifactor analysis showed that the Karnofsky performance scale (P = 0.01), World Health Organization grade (P = 0.008) and neuroepithelial-transforming protein 1 (P = 0.006) were independent prognosis factors for human glioma. CONCLUSIONS: Taken together, our study indicates for the first time that neuroepithelial-transforming protein 1 status may be a highly sensitive marker for glioma prognosis and suggest that the expression patterns of neuroepithelial-transforming protein 1 might be a potent tool for predicting the clinical prognosis of glioma patients.
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Biomarcadores de Tumor/metabolismo , Neoplasias Encefálicas/patología , Glioma/patología , Proteínas Oncogénicas/metabolismo , Estudios de Casos y Controles , China , Femenino , Humanos , Inmunohistoquímica , Estado de Ejecución de Karnofsky , Masculino , Persona de Mediana Edad , Análisis Multivariante , Valor Predictivo de las Pruebas , Pronóstico , Análisis de SupervivenciaRESUMEN
OBJECTIVE: To construct three recombinant shuttle plasmids of adenovirus expression vector which can express hepatitis C virus(HCV) different structure genes(C, C+E1, C+E1+E2) in order to pack adenovirus expression vectors which can express HCV different structure gene effectively. METHODS: The different HCV structure genes derived from the plasmid pBRTM/HCV1-3011 by using polymerase chain reaction (PCR) were inserted into the backward position of cytomegalovirus(CMV) immediate early promotor element of shuttle plasmid(pAd.CMV-Link.1) of adenovirus expression vector respectively, then the three recombinant plasmids (pAd.HCV-C, pAd.HCV-CE1, pAd.HCV-S) were obtained. The recombinant plasmids were identified by endonuclease, PCR and sequencing. HCV structure genes were expressed transiently with Lipofectamine 2000 coated in HepG2 cells which were confirmed by immunofluorescence and Western-Blot. RESULTS: Insert DNAs of the three recombinant plasmids' were confirmed to be HCV different structure genes by endonuclease, PCR and sequencing. The three recombinant plasmids can express HCV structure gene (C, C+E1, C+E1+E2) transiently in HepG2 cells which were confirmed by immunofluorescence and Western-Blot. CONCLUSION: The three recombinant shuttle plasmids of adenovirus expression vector can express HCV structure gene(C, C+E1, C+E1+E2) transiently. This should be useful to pack adenovirus expression vector which can express HCV structure genes.
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Adenoviridae/genética , Vectores Genéticos , Hepacivirus/genética , Proteínas Estructurales Virales/genética , Expresión Génica , Estructura Molecular , PlásmidosRESUMEN
AIM: To set up a new method to detect tissue inhibitors of metalloproteinase-1 and -2(TIMP-1 and TIMP-2) in sera of patients with hepatic cirrhosis, and to investigate the expression and location of TIMP-1 and TIMP-2 in liver tissue of patients with hepatic cirrhosis, and the correlation between TIMPs in liver and those in sera so as to discuss whether TIMPs can be used as a diagnosis index of hepatic fibrosis. METHODS: The monoclonal antibodies (McAbs) of TIMP-1 and TIMP-2 were used to sensitize erythrocytes, and solid-phase absorption to sensitized erythrocytes (SPASE) was used to detect TIMP-1 and TIMP-2 in the sera of patients with hepatic cirrhosis. Meanwhile, with the method of in situ hybridization and immunohistochemistry, we studied the mRNA expression and antigen location of TIMP-1 and TIMP-2 in the livers of 40 hepatic cirrhosis patients with pathologic diagnosis. RESULTS: With SPASE, they were 16.4% higher in the acute hepatitis group, 33.3% higher in the chronic hepatitis group, and the positive rates were 73.6% and 61.2% respectively in sera of hepatic cirrhosis patients, which were remarkably higher than those in chronic hepatitis and acute hepatitis group (P<0.001). In 40 samples of hepatic cirrhosis tissues, all of them showed positive expression of TIMP-1 and TIMP-2 mRNA detected with immunohistochemistry or in situ hybridization (positive rate was 100%). Expression of TIMPs in different degrees could be found in liver tissue with cirrhosis. TIMPs were located in cytoplasm of liver cells of patients with hepatic cirrhosis. There was a significant correlation between serum TIMPs level and liver TIMPs level. CONCLUSION: SPASE is a useful method to detect the TIMP-1 and TIMP-2 in sera of patients with hepatic cirrhosis, and TIMP-1 and TIMP-2 can be considered as a useful diagnostic index of hepatic fibrosis, especially TIMP-1.
Asunto(s)
Inmunoensayo/métodos , Cirrosis Hepática/diagnóstico , Inhibidor Tisular de Metaloproteinasa-1/metabolismo , Inhibidor Tisular de Metaloproteinasa-2/metabolismo , Anticuerpos Monoclonales/metabolismo , Eritrocitos/metabolismo , Humanos , Hibridación in Situ , Hígado/metabolismo , Cirrosis Hepática/metabolismo , Inhibidores de Proteasas/metabolismo , Inhibidor Tisular de Metaloproteinasa-1/genética , Inhibidor Tisular de Metaloproteinasa-2/genéticaRESUMEN
Objective. To investigate the rule of intensity and duration of HSP70 expression in rat brain and its relationship with brain injury after repeated +Gz exposures. Method. SD male rats were arranged into control group, +2 Gz, +4 Gz, +6 Gz, and +10 Gz exposure groups. Rat brains were taken 6 h, 10 h, 1 d, 2 d, 4 d or 6 d after +Gz exposure for histopathologic and immunohistochemic or in situ hybridization studies. The expression of HSP70 and HSP70 mRNA or morphology of neurons were observed. Result. The intensity and duration of HSP70 expression were weak and brief at +2 Gz exposure, but was relatively extensive. There was a middling reaction of HSP70 only in hippocampal area after +10 Gz exposure. The duration, extension and intensity of HSP70 expression were wide, long and strong after +4 Gz and +6 Gz exposures. After 1 or 3-5 times exposures, the HSP70 expression reached its peak on the first day after +4 Gz exposures, and dropped obviously on the second day. However the expression of HSP70 maintained a high level after 2 d and was still higher than normal on the 6 d after 3-5 times repeated +4 Gz exposures. The distribution of HSP70 mRNA expression was as same as that of the HSP70 expression but the peak appeared much earlier (10 h) and its duration was shorter. After +10 Gz/5 min exposure, degenerated neurons were found in cortex, hippocampus and thalamus regions while the number of degenerated neurons were obviously decreased in such areas in pre-exposure groups with repeated +4 Gz/3 min for 3-5 times. Conclusion. The intensity and duration of HSP70 and HSP70 mRNA expression after +4 Gz and +6 Gz exposure were stronger and longer than +2 Gz and +10 Gz exposure. The degree of neuron damage after +10 Gz/5 min exposure in pre-exposure groups with repeated +4 Gz/3 min 3-5 times was obviously slight comparing with that of single +10 Gz exposure group.