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CKD is a clinical syndrome with slow development and gradual deterioration of renal function. At present, modern medicine still lacks an ideal treatment method for this disease, while TCM has accumulated rich clinical experience in the treatment of CKD, which can effectively improve renal function and delay renal failure, and has unique advantages. RC is widely used in clinical practice to treat CKD, especially the "Kidney-Yin" deficiency syndrome. However, the compatibility mechanisms responsible for its effects in experimental studies, including preclinical and clinical research studies, are still not fully understood. Adenine-induced CKD rats were used to investigate the preventive effect of RC on CKD rats. Based on the high-throughput 16S rRNA gene sequencing results from Illumina, we discussed the intestinal flora abundance in rats in different treatment groups. According to a PCA and a PCoA based on a distance matrix, there was a clear separation of gut microbiome profiles between normal rats and model rats in terms of beta diversity. The abundance of Firmicutes in CKD rats was relatively increased, while that of Bacteroidetes was decreased. It is clear that the plot for the RC group was closer to that of the normal group, suggesting that the RC group had higher similarities among bacterial members with N rats. Ussing chamber, Western blot, and PCR assays were used to investigate the effects of RC on intestinal barrier function and its molecular mechanism in model animals. The results indicated that the protein expressions of ZO-1, claudin-1, and occludin-1 were decreased significantly in chronic kidney disease rats with the induction of adenine. With the treatment of RG, CO, and RC, the intestinal barrier was repaired due to the upregulated expressions of the aforementioned proteins in CKD rats. Based on our findings, RC appears to strengthen the intestinal barrier and modulate gut microbiota in adenine-induced CKD rats. This project revealed the compatibility mechanism of RC in regulating the intestinal microecology and barrier function to intervene in CKD and provided the basis and ideas for the clinical application of RC and the development of innovative drugs for CKD.
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AIM: To determine the effect of osteopontin (OPN) on autophagy and autophagy-apoptosis interactions after SAH. METHODS: The endovascular perforation model of SAH or sham surgery was performed in a total of 86 Sprague-Dawley male rats. The temporal expressions of endogenous OPN and autophagy-related proteins (Beclin 1, ATG5, LC3 II to I ratio) were measured in sham and SAH rats at different time points (3, 6, 12, 24, and 72 hours). Rats were randomly divided into three groups: Sham, SAH + Vehicle (PBS, phosphate-buffered saline), and SAH + rOPN (5 µg/rat recombinant OPN). Neurobehavioral tests were performed 24 hours after SAH, followed by the collection of brain samples for assessment of autophagy and apoptosis proteins. These tests assessed whether an autophagy-apoptosis relationship existed on the histological level in the brain. RESULTS: Endogenous OPN and autophagy-related proteins all increased after SAH. rOPN administration improved neurological dysfunction, increased the expression of autophagy-related proteins (Beclin 1, ATG5, LC3 II to I ratio) and antiapoptotic protein Bcl-2, while decreasing the expression of proapoptotic proteins (cleaved Caspase-3 and Bax). rOPN also regulated autophagy-apoptosis interactions 24 hours after SAH. CONCLUSION: rOPN attenuates early brain injury and inhibits neuronal apoptosis by activating autophagy and regulating autophagy-apoptosis interactions.
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Apoptosis/fisiología , Autofagia/fisiología , Lesiones Encefálicas/metabolismo , Lesiones Encefálicas/prevención & control , Osteopontina/administración & dosificación , Hemorragia Subaracnoidea/metabolismo , Administración Intranasal , Animales , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Lesiones Encefálicas/patología , Masculino , Osteopontina/biosíntesis , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Hemorragia Subaracnoidea/tratamiento farmacológico , Hemorragia Subaracnoidea/patologíaRESUMEN
Early tumor recurrence after curative surgical resection poses a great challenge to the clinical management of hepatocellular carcinoma (HCC). We conducted whole genome expression microarrays on 64 primary HCC tumors with clinically defined recurrence status and cross-referenced with RNA-seq data from 18 HCC tumors in the Cancer Genome Atlas project. We identified a 77-gene signature, which is significantly associated with early recurrent (ER) HCC tumors. This ER-associated signature shows significant enrichment in genes involved in cell cycle pathway. We performed receiver operating characteristic (ROC) analysis to evaluate the prognostic biomarker potential of these 77 genes and Pearson correlation analysis to identify 11 close clusters. The one gene with the best area under the ROC curve in each of the 11 clusters was selected for validation using reverse-transcription quantitative PCR in an independent cohort of 24 HCC tumors. NUF2 was identified to be the minimal biomarker sufficient to discriminate ER tumors from LR tumors. NUF2 in combination with liver cirrhosis could significantly improve the detection of ER tumors with an AUROC of 0.82 and 0.85 in the test and validation cohort, respectively. In conclusion, NUF2 in combination with liver cirrhosis is a promising prognostic biomarker for early HCC recurrence.
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Carcinoma Hepatocelular/metabolismo , Proteínas de Ciclo Celular/metabolismo , Neoplasias Hepáticas/metabolismo , Recurrencia Local de Neoplasia/metabolismo , Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/cirugía , Estudios de Cohortes , Femenino , Humanos , Cirrosis Hepática/metabolismo , Cirrosis Hepática/patología , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Valor Predictivo de las Pruebas , Tasa de Supervivencia , TranscriptomaRESUMEN
PURPOSE: This study aims to determine the indications and effectiveness of transnasal endoscopic prelacrimal recess approach (PLRA) in patients with maxillary sinus inverted papilloma (IP). METHODS: We retrospectively analyzed 71 patients treated in our institution for maxillary sinus IP between August 2008 and April 2015. 20 patients underwent endoscopic surgery via PLRA. All the patients who had postoperative follow-up for 3 years were enrolled. Demographic data, surgical technique, location of IP attachment, intra- and postoperative complications, follow-up duration and recurrence were recorded. RESULTS: The outpatient follow-up period was 3-10 years after surgery. Recurrence of IP was seen in 6 (8.5%) of 71 patients, including 1 patient in the PLRA group. The recurrence rate was 5% in the PLRA group. Six of 71 patients experienced postoperative complications, but none was observed in the PLRA group. CONCLUSION: Transnasal endoscopic PLRA is a minimally invasive, safe and effective method for maxillary sinus IP. The indication for PLRA is tumor pedicle located on the antero-inferior or infero-lateral wall or at multiple attachment sites of the maxillary sinus.
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Neoplasias del Seno Maxilar/cirugía , Cirugía Endoscópica por Orificios Naturales/métodos , Recurrencia Local de Neoplasia/epidemiología , Papiloma Invertido/cirugía , Complicaciones Posoperatorias/epidemiología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cirugía Endoscópica por Orificios Naturales/efectos adversos , Selección de Paciente , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Sinonasal inverted papilloma (SNIP) is noted for its high rate of recurrence and malignant transformation. Although many clinical studies have demonstrated the effectiveness of the endoscopic approach for SNIP, the surgical strategy has been the subject of much debate. OBJECTIVE: To evaluate the effectiveness of the endoscopic endonasal approach in SNIP. METHODS: A systematic review of patients with a diagnosis of SNIP and who had surgery at our institution from June 2005 to March 2013 was performed. All the patients who had postoperative follow-up for >2 years were enrolled. Each case was categorized into one of four stages as reported by Krouse. Demographic and tumor date, operative approach, complications, and recurrence rates were collected. RESULTS: A total of 125 patients were included in this study. There were 17 patients in stage 1, 40 in stage 2, 57 in stage 3, and 11 in stage 4. The overall recurrence rate was 8.0%. There was no significant difference in recurrence among the stages (all p > 0.05). Recurrence after endoscopic endonasal approach (8.4%) and a combined endoscopic and open exposure procedure (5.6%) were not significantly different (p > 0.05). The recurrence rate was significantly (p < 0.05) higher in patients with revision (15.6%) than in patients in the primary cases (3.8%). A common site of tumor origin was recorded to be from the maxillary sinus (40.2%). Twenty percent of recurrences were observed up to 5 years after surgery. CONCLUSION: Endoscopic surgery may be preferred for treating SNIP. The elevated recurrence rate after revision emphasized the significance of the first surgery. We encourage a follow-up period of at least 5 years.
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Endoscopía , Seno Maxilar/cirugía , Papiloma Invertido/cirugía , Neoplasias de los Senos Paranasales/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Papiloma Invertido/patología , Neoplasias de los Senos Paranasales/patología , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Gliomas are the most common type of primary brain tumour in the central nervous system of adults. The long non-coding RNA (lncRNA) HOXA transcript at the distal tip (HOTTIP) is transcribed from the 5' tip of the HOXA locus. HOTTIP has recently been shown to be dysregulated and play an important role in the progression of several cancers. However, little is known about whether and how HOTTIP regulates glioma development. METHODS: In this study, we assayed the expression of HOTTIP in glioma tissue samples and glioma cell lines using real-time polymerase chain reaction and defined the biological functions of HOTTIP using the CCK-8 assay, flow cytometry, terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL assay) and tumour formation assay in a nude mouse model. Finally, we discovered the underlying mechanism using the Apoptosis PCR 384HT Array, Western blot, RNA immunoprecipitation (RIP) and luciferase reporter assay. RESULTS: HOTTIP was aberrantly down-regulated in glioma tissues and glioma cell lines (U87-MG, U118-MG, U251 and A172), and over-expression of HOTTIP inhibited the growth of glioma cell lines in vitro and in vivo. Furthermore, HOTTIP could directly bind to the brain and reproductive expression (BRE) gene and down-regulate BRE gene expression. In addition, we further verified that over-expression of the BRE gene promoted the growth of glioma cell lines in vitro. Finally, over-expression of HOTTIP significantly suppressed the expression of the cyclin A and CDK2 proteins and increased the expression of the P53 protein. However, we found that the over-expression of BRE significantly increased the expression of the cyclin A and CDK2 proteins and suppressed the expression of the P53 protein. Taken together, these findings suggested that high levels of HOTTIP reduced glioma cell growth. Additionally, the mechanism of HOTTIP-mediated reduction of glioma cell growth may involve the suppression of cyclin A and CDK2 protein expression, which increases P53 protein expression via the down-regulation of BRE. CONCLUSIONS: Our studies demonstrated that over-expression of HOTTIP promotes cell apoptosis and inhibits cell growth in U118-MG and U87-MG human glioma cell lines by down-regulating BRE expression to regulate the expression of P53, CDK2 and Cyclin A proteins. The data described in this study indicate that HOTTIP is an interesting candidate for further functional studies in glioma and demonstrate the potential application of HOTTIP in glioma therapy.
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Neoplasias Encefálicas/patología , Glioma/patología , Proteínas del Tejido Nervioso/genética , ARN Largo no Codificante/genética , Regulación hacia Arriba , Regiones no Traducidas 3' , Animales , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Línea Celular Tumoral , Proliferación Celular , Ciclina A/metabolismo , Quinasa 2 Dependiente de la Ciclina/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Glioma/genética , Glioma/metabolismo , Humanos , Masculino , Ratones , Trasplante de Neoplasias , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
OBJECTIVE: To observe the time course of proliferation and differentiation of neural stem cells (NSCs) in the subventricular zone (SVZ) of rats following traumatic craniocerebral injury (TBI). METHODS: Forty-eight SD rats were randomized into 3 groups, namely the control group without any treatment, the sham-operated group with scalp incision and preparation of a cranial window, and TBI group with craniocerebral injury induced by Feeney's method. With nestin and BrdU as two cell markers, NSE as the neuron-specific marker and GFAP as the glial cell marker, immunofluorescence assay with double labeled antibodies was performed to examine the proliferation and differentiation of endogenous NSCs in the SVZ at different time points after TBI. RESULTS: s The numbers of cells positive for nestin/NSE, nestin/GFAP, BrdU/NSE, and BrdU/GFAP in the SVZ of the rats increased significantly after TBI. The positive cells began to increase at 1 day after TBI, reached the peak level at day 3 and became normal at day 14, showing significant differences between the time points of measurement following TBI and from the cell numbers in the control group measured at the same time points. The cells positive for nestin/ GFAP showed the most distinct increase in the SVZ of the rats with TBI. CONCLUSION: TBI results in mobilization of the NSCs in the SVZ on the injured side to cause the proliferation and differentiation of the endogenous NSCs. The SVZ is one of the most important germinal centers of NSC proliferation and differentiation.
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Diferenciación Celular , Proliferación Celular , Traumatismos Craneocerebrales/patología , Ventrículos Laterales/citología , Células-Madre Neurales/citología , Animales , Bromodesoxiuridina/metabolismo , Proteína Ácida Fibrilar de la Glía/metabolismo , Nestina/metabolismo , Neuroglía/citología , Neuronas/citología , Fosfopiruvato Hidratasa/metabolismo , Distribución Aleatoria , Ratas , Ratas Sprague-DawleyRESUMEN
The poor therapeutic effect of traditional antiangiogenic therapy on glioblastoma multiforme (GBM) may be attributed to vasculogenic mimicry (VM), which was previously reported to be promoted by cancer stem-like cells (SLCs). All-trans retinoic acid (ATRA), a potent reagent which drives differentiation, was reported to be able to eradicate cancer SLCs in certain malignancies. The aim of the present study was to investigate the effects of ATRA on the VM formation ability of U87 glioblastoma SLCs. The expression of cancer SLC markers CD133 and nestin was detected using immunocytochemistry in order to identify U87 SLCs. In addition, the differentiation of these SLCs was observed through detecting the expression of glial fibrillary acidic protein (GFAP), ß-tubulin III and galactosylceramidase (Galc) using immunofluorescent staining. The results showed that the expression levels of GFAP, ß-tubulin III and Galc were upregulated following treatment with ATRA in a dose-dependent manner. Furthermore, ATRA significantly reduced the proliferation, invasiveness, tube formation and vascular endothelial growth factor (VEGF) secretion of U87 SLCs. In conclusion, the VM formation ability of SLCs was found to be negatively correlated with differentiation. These results therefore suggested that ATRA may serve as a promising novel agent for the treatment of GBM due to its role in reducing VM formation.
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Inhibidores de la Angiogénesis/farmacología , Biomarcadores de Tumor/genética , Células Madre Neoplásicas/efectos de los fármacos , Neovascularización Patológica/prevención & control , Neuroglía/efectos de los fármacos , Tretinoina/farmacología , Antígeno AC133 , Antígenos CD/genética , Antígenos CD/metabolismo , Biomarcadores de Tumor/metabolismo , Diferenciación Celular/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Galactosilceramidasa/genética , Galactosilceramidasa/metabolismo , Expresión Génica , Proteína Ácida Fibrilar de la Glía/agonistas , Proteína Ácida Fibrilar de la Glía/genética , Proteína Ácida Fibrilar de la Glía/metabolismo , Glicoproteínas/genética , Glicoproteínas/metabolismo , Humanos , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Neovascularización Patológica/genética , Neovascularización Patológica/metabolismo , Nestina/genética , Nestina/metabolismo , Neuroglía/metabolismo , Neuroglía/patología , Péptidos/genética , Péptidos/metabolismo , Tubulina (Proteína)/agonistas , Tubulina (Proteína)/genética , Tubulina (Proteína)/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Adipocyte-derived stem cells have emerged as a novel source of stem cell therapy for their autologous and readily accessible and pluripotent potential to differentiate into different lineages such as neural stem cells (NSCs) and endothelial progenitor cells (EPCs). Transplantation of NSCs and EPCs has been promising for the repair of brain injury. We explored using co-transplanted hydrogel scaffold to improve the survival of the transplanted cells and recovery of neurological function. Adult Wistar rats were transplanted with EPC-hydrogel, NSC-hydrogel, NSC-EPC-hydrogel, EPC only, or NSC only 7 days after cortical contusion injury. Behavioral tests were performed to evaluate neurological function before, and 1, 2, 3, and 4 weeks after transplantation. Size of injury, extent of vascularization, as well as the survival and differentiation of the transplanted EPCs and NSCs, were evaluated at week 5. All transplantation groups displayed significantly better neurological function compared with the control groups. Improved neurological function correlated with significantly smaller injury volumes than that of the saline group. Using immunostaining, we have shown that while transplanted NSCs differentiated into both neurons and astrocytes, the EPCs were incorporated into vessel epithelia. The extent of reactive gliosis (based on glial fibrillary acidic protein immunostaining) was significantly reduced in all treatment groups (NSC-EPC-hydrogel, NSC-hydrogel, and EPC-hydrogel) when compared with the saline group, with the highest reduction in the NSC-EPC-hydrogel transplantation group. Thus, co-transplantation of hydrogel scaffold provides a more conducive environment for the survival and differentiation of NSCs and EPCs at the site of brain injury, leading to improved vascularization and better recovery of neurological function.
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Adipocitos/trasplante , Lesiones Encefálicas/terapia , Recuperación de la Función/fisiología , Trasplante de Células Madre/métodos , Animales , Conducta Animal/fisiología , Lesiones Encefálicas/fisiopatología , Modelos Animales de Enfermedad , Hidrogel de Polietilenoglicol-Dimetacrilato , Masculino , Actividad Motora/fisiología , Ratas , Ratas Wistar , Andamios del Tejido , Resultado del TratamientoRESUMEN
BACKGROUND: Previous studies have shown beneficial effects of mesenchymal stem cell (MSC) transplantation in central nervous system (CNS) injuries, including traumatic brain injury (TBI). Potential repair mechanisms involve transdifferentiation to replace damaged neural cells and production of growth factors by MSCs. However, few studies have simultaneously focused on the effects of MSCs on immune cells and inflammation-associated cytokines in CNS injury, especially in an experimental TBI model. In this study, we investigated the anti-inflammatory and immunomodulatory properties of MSCs in TBI-induced neuroinflammation by systemic transplantation of MSCs into a rat TBI model. METHODS/RESULTS: MSCs were transplanted intravenously into rats 2 h after TBI. Modified neurologic severity score (mNSS) tests were performed to measure behavioral outcomes. The effect of MSC treatment on neuroinflammation was analyzed by immunohistochemical analysis of astrocytes, microglia/macrophages, neutrophils and T lymphocytes and by measuring cytokine levels [interleukin (IL)-1α, IL-1ß, IL-4, IL-6, IL-10, IL-17, tumor necrosis factor-α, interferon-γ, RANTES, macrophage chemotactic protein-1, macrophage inflammatory protein 2 and transforming growth factor-ß1] in brain homogenates. The immunosuppression-related factors TNF-α stimulated gene/protein 6 (TSG-6) and nuclear factor-κB (NF-κB) were examined by reverse transcription-polymerase chain reaction and Western blotting. Intravenous MSC transplantation after TBI was associated with a lower density of microglia/macrophages and peripheral infiltrating leukocytes at the injury site, reduced levels of proinflammatory cytokines and increased anti-inflammatory cytokines, possibly mediated by enhanced expression of TSG-6, which may suppress activation of the NF-κB signaling pathway. CONCLUSIONS: The results of this study suggest that MSCs have the ability to modulate inflammation-associated immune cells and cytokines in TBI-induced cerebral inflammatory responses. This study thus offers a new insight into the mechanisms responsible for the immunomodulatory effect of MSC transplantation, with implications for functional neurological recovery after TBI.
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Lesiones Encefálicas/inmunología , Lesiones Encefálicas/cirugía , Inmunomodulación/fisiología , Trasplante de Células Madre Mesenquimatosas/métodos , Animales , Lesiones Encefálicas/patología , Modelos Animales de Enfermedad , Inflamación/inmunología , Inflamación/prevención & control , Inflamación/cirugía , Ratas , Ratas Sprague-DawleyRESUMEN
Glioma stem cells (GSCs) are thought to be critical for resistance to radiotherapy and chemotherapy and for tumor recurrence after surgery in glioma patients. Identification of new therapeutic strategies that can target GSCs may thus be critical for improving patient survival. MicroRNAs (miRNAs) are small non-coding RNAs that function as tumor suppressors or oncogenes. In this study, we confirmed that miR-107 was down-regulated in GSCs. To investigate the role of miR-107 in tumorigenesis of GSCs, a lentiviral vector over-expressing miR-107 in U87GSCs was constructed. We found that over-expression of miR-107 suppressed proliferation and down-regulated Notch2 protein and stem cell marker (CD133 and Nestin) expression in U87GSCs. Furthermore, enhanced miR-107 expression significantly inhibited U87GSC invasion and reduced matrix metalloproteinase-12 expression. miR-107 also suppressed U87GSCs xenograft growth in vivo. These findings suggest that miR-107 is involved in U87GSCs growth and invasion and may provide a potential therapeutic target for glioma treatment.
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Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Glioma/genética , Glioma/patología , MicroARNs/metabolismo , Células Madre Neoplásicas/patología , Antígeno AC133 , Animales , Antígenos CD/metabolismo , Secuencia de Bases , Neoplasias Encefálicas/enzimología , Línea Celular Tumoral , Proliferación Celular , Regulación hacia Abajo/genética , Regulación Neoplásica de la Expresión Génica , Glioma/enzimología , Glicoproteínas/metabolismo , Humanos , Lentivirus/metabolismo , Metaloproteinasa 12 de la Matriz/metabolismo , Ratones , Ratones Desnudos , MicroARNs/genética , Datos de Secuencia Molecular , Invasividad Neoplásica , Células Madre Neoplásicas/enzimología , Nestina/genética , Nestina/metabolismo , Péptidos/metabolismo , Receptor Notch2/genética , Receptor Notch2/metabolismo , Transducción Genética , Regulación hacia Arriba/genética , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
A previous report has confirmed the existence and clinical significance of vasculogenic mimicry (VM) in glioma. However, its conclusions about the negative clinical significance of VM in glioblastoma are based on a small group of patients and, thus, might be unconvincing. The aim of the present study was to reevaluate the clinical significance of VM in glioblastoma. Patients were classified as VM-positive or VM-negative according to CD34 and periodic acid-Schiff staining. The association between VM and the clinical characteristics of the patients was analyzed. Univariate and multivariate analyses were carried out to identify the independent prognostic factors for overall survival using the Cox regression hazard model. Survival times were estimated using the Kaplan-Meier method and compared using the log-rank test. Of all 86 glioblastomas, 23 were found to have VM. The presence of VM in glioblastoma was not associated with gender, age, Karnofsky performance status, hydrocephalus, tumor burden, microvessel density, tumor relapse, or the extent of tumor resection. The univariate and multivariate analyses revealed that VM is an independent prognostic factor for overall survival. The median survival time for patients with VM was 11.17 months compared with 16.10 months for those without VM (P = 0.017). In addition to VM, an age of 65 years or older, a KPS of 60 or less, a large tumor burden are significant prognostic factors for patient survival. Our data suggest that VM might be an independent adverse prognostic factor in newly diagnosed GBM, further prospective studies are needed to answer this question.
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Neoplasias Encefálicas/irrigación sanguínea , Neoplasias Encefálicas/patología , Glioblastoma/irrigación sanguínea , Glioblastoma/patología , Adolescente , Adulto , Anciano , Antígenos CD34/análisis , Antígenos CD34/biosíntesis , Neoplasias Encefálicas/mortalidad , Femenino , Glioblastoma/mortalidad , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Adulto JovenRESUMEN
MicroRNAs (miRNAs), small non-protein-coding RNA molecules, modulate target gene expression by binding to 3'untranslated regions (UTR) of target mRNA. These molecules are aberrantly expressed in many human cancers, and can function either as tumor suppressors or oncogenes. In the current study, we show that miR-107 is down-regulated in glioma tissues and cell lines, and its overexpression leads to inhibition of the migratory and invasive ability of glioma cells via direct targeting of Notch2, which is known to transactivate Tenascin-C and Cox-2. Experiments with Notch2 siRNA further suggest that miR-107 may exerts its anti-invasive activity through Notch2 signaling pathways. Our findings collectively indicate that miR-107 is involved in glioma cell migration and invasion, and support its utility as a potential target for glioma treatment.
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Movimiento Celular/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/fisiología , MicroARNs/metabolismo , Invasividad Neoplásica/genética , Receptor Notch2/metabolismo , Análisis de Varianza , Línea Celular Tumoral , Ciclooxigenasa 2/metabolismo , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Glioma/patología , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Humanos , Técnicas In Vitro , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 2 de la Matriz/metabolismo , MicroARNs/genética , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Receptor Notch2/genética , Tenascina/metabolismo , Transfección , Cicatrización de Heridas/efectos de los fármacos , Cicatrización de Heridas/genéticaRESUMEN
OBJECTIVE: The purpose of this study was to evaluate the safety and efficacy of transorbital puncture for the retreatment of previously embolized cavernous sinus dural arteriovenous fistulas (DAVFs) via a superior ophthalmic vein (SOV) approach. MATERIALS AND METHODS: During a 12-year period, 9 consecutive patients with previously embolized cavernous sinus DAVFs underwent retreatment via the transorbital SOV approach. RESULTS: All of the nine cases of previously embolized cavernous sinus DAVFs were successfully embolized. Clinical follow-ups were conducted in all nine cases at the duration of 17-141 months (61.22 ± 39.13 months). No recanalization occurred during the follow-up period. A subtle ptosis appeared in two patients and disappeared in one of the two cases after a 4-year follow-up. One patient suffered from paroxysmal positional vertigo and bruit for nearly 2 years after the treatment, but the follow-up angiography demonstrated no recurrence. One patient had persistent visual impairment caused by the initial venous stasis retinopathy. One patient with a history of a procedure-related transient decrease in visual acuity had it return to the normal level. The remaining four cases had clear improvement in the ocular symptoms and became completely asymptomatic during the follow-up period. No patient worsened or developed new symptoms. CONCLUSION: The approach of surgical cannulation of the SOV for the retreatment of previously embolized cavernous sinus DAVFs was proved feasible and efficient, especially when the transarterial and transfemoral venous approaches were inaccessible. However, if the SOV is not dilated enough or is located deeply in the orbit, transorbital venous puncture access may not be possible.
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Cateterismo/métodos , Seno Cavernoso/anomalías , Malformaciones Vasculares del Sistema Nervioso Central/terapia , Ojo/irrigación sanguínea , Venas/cirugía , Adulto , Anciano , Seno Cavernoso/diagnóstico por imagen , Malformaciones Vasculares del Sistema Nervioso Central/diagnóstico por imagen , Embolización Terapéutica , Procedimientos Endovasculares/métodos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Radiografía , Retratamiento , Estudios Retrospectivos , Trombosis de la Vena/cirugía , Adulto JovenRESUMEN
MicroRNAs (miRNAs) are small noncoding RNAs that function as tumor suppressors or oncogenes. MicroRNA-107 (miR-107), a transcriptional target of p53, is deregulated in many cancer cell lines. Here, we showed that miR-107 is down-regulated in glioma tissues and cell lines, in particular, p53-mutated U251 and A172. Transfection of wild-type p53 into these cells stimulated miR-107 expression. To investigate the role of miR-107 in tumorigenesis, we constructed a lentiviral vector overexpressing miR-107. Notably, miR-107 inhibited proliferation and arrested the cell cycle at the G0-G1 phase in glioma cells. Transduction of Lenti-GFP-miR-107 into glioma cells inhibited CDK6 and Notch-2 protein expression. Our findings collectively demonstrate that p53-induced miR-107 suppresses brain tumor cell growth and down-regulates CDK6 and Notch-2 expression, supporting its tumor suppressor role and utility as a target for glioma therapy.
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Quinasa 6 Dependiente de la Ciclina/biosíntesis , MicroARNs/metabolismo , Receptor Notch2/biosíntesis , Proteína p53 Supresora de Tumor/metabolismo , Línea Celular Tumoral , Proliferación Celular , Regulación hacia Abajo , Glioma , Humanos , Lentivirus/genética , MicroARNs/genética , Transducción Genética , Transfección , Proteína p53 Supresora de Tumor/genéticaRESUMEN
Tenascin-R (TN-R) is a neural specific protein and an important molecule involved in inhibition of axonal regeneration after spinal cord injury (SCI). Here we report on rabbit-derived TN-R polyclonal antibody, which acts as a TN-R antagonist with high titer and high specificity, promoted neurite outgrowth and sprouting of rat cortical neurons cultured on the inhibitory TN-R substrate in vitro. When locally administered into the lesion sites of rats received spinal cord dorsal hemisection, these TN-R antibodies could significantly decrease RhoA activation and improve functional recovery from corticospinal tract (CST) transection. Thus, passive immunotherapy with specific TN-R antagonist may represent a promising repair strategy following acute SCI.
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Anticuerpos/farmacología , Axones/efectos de los fármacos , Traumatismos de la Médula Espinal/terapia , Tenascina/antagonistas & inhibidores , Animales , Animales Recién Nacidos , Anticuerpos/uso terapéutico , Axones/fisiología , Células Cultivadas , Femenino , Miembro Posterior/fisiopatología , Inmunización Pasiva , Actividad Motora , Regeneración Nerviosa , Neuritas/efectos de los fármacos , Neuritas/fisiología , Conejos , Ratas , Ratas Sprague-Dawley , Traumatismos de la Médula Espinal/inmunología , Traumatismos de la Médula Espinal/fisiopatología , Tenascina/inmunología , Proteína de Unión al GTP rhoA/metabolismoRESUMEN
BACKGROUND: Interleukin-l7 (IL-17), which exerts strong pro-inflammatory effects, has emerged as an important mediator in inflammation-associated cancer. The aim of this study was to clarify the relationship between IL-17 and tumor associated macrophages (TAMs), and the correlation of the microvessel density in the development of laryngeal squamous cell carcinoma (LSCC). METHODS: Histopathological observations and immunohistochemistry staining for IL-17, CD68, and CD34 were performed on 72 specimens (32 cases of LSCC, 20 cases of adjacent tissues of carcinoma as controls, and 20 cases of chronic hypertrophic laryngitis). Double immunohistochemical staining was done to determine which cells expressed IL-17. Real-time quantitative PCR determined the mRNA expression of IL-17. ELISA was used to detect the expression of the serum level of IL-17 in the three groups. RESULTS: The inflammation response had increased in LSCC. Overexpression of IL-17 and CD68 protein were seen in LSCC (P < 0.01). The expression of IL-17 was different between well and poorly differentiated LSCC (P < 0.01). The IL-17 expressing cells were mainly located in macrophages (CD68(+)/IL17(+)) as demonstrated by double immunohistochemical staining. IL-17 expression significantly correlated with high microvessel density (CD34(+)) in LSCC (P < 0.05). Relatively higher mRNA expression levels of IL-17 were seen in LSCC compared to the controls (P < 0.05). The serum expression of IL-17 was similar among the three groups (P > 0.05). CONCLUSION: IL-17 was expressed by TAMs, and IL-17 may significantly correlate to the differentiation and angiogenesis in the development of LSCC.
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Carcinoma de Células Escamosas/metabolismo , Interleucina-17/metabolismo , Neoplasias Laríngeas/metabolismo , Macrófagos/metabolismo , Adulto , Anciano , Carcinoma de Células Escamosas/genética , Femenino , Humanos , Inmunohistoquímica , Interleucina-17/genética , Neoplasias Laríngeas/genética , Masculino , Persona de Mediana Edad , Neovascularización Patológica/genética , Neovascularización Patológica/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Adulto JovenRESUMEN
Human placental decidua basalis-derived mesenchymal stem cells (DBMSCs) have been identified as valuable sources for cell transplantation. In this study, we found that DBMSCs could be induced to form neural stem cells in the form of neurospheres. These neurospheres were further differentiated into dopamine neuron-like cells with a cocktail of cytokines. The differentiated DBMSCs were verified through the presence of a neuron-like morphology, the expression of specific dopamine neuron makers, and the production of dopamine. In addition, this differentiation capacity of DBMSCs was not affected by long-term culture, and the cells maintained a normal karyotype in vitro. The dopamine neuronal differentiation and the relative safety transplantation potential of DBMSCs may facilitate stem cell therapeutic approaches to Parkinson's disease.
Asunto(s)
Diferenciación Celular/fisiología , Decidua/citología , Neuronas Dopaminérgicas/fisiología , Células Madre Mesenquimatosas/citología , Antígenos CD/metabolismo , Células Cultivadas , Cromatografía Líquida de Alta Presión , Dopamina/metabolismo , Femenino , Humanos , Recién Nacido , Cariotipificación , Masculino , Proteínas del Tejido Nervioso/metabolismo , EmbarazoRESUMEN
Vasculogenic mimicry (VM), a process involving the formation of a tubular structure by highly invasive and genetically dysregulated tumor cells, can supplement the function of blood vessels to transport nutrients and oxygen to maintain the growth of tumor cells in many malignant tumors. We aimed to explore the existence of VM and its clinical significance in medulloblastoma in this study. VM was identified in 9 out of 41 (22%) medulloblastoma tissues. Immunohistochemical studies revealed that the presence of VM was associated with the expression of MMP-2, MMP-14, EphA2 and laminin 5γ2. Tumor tissues with VM were associated with lower microvessel density (MVD), which was indirect evidence of the blood supply function of VM. Survival analysis and log-rank tests showed that patients with VM had shorter overall survival time than those without VM. Multivariate analysis and the Cox proportional hazards model identified VM as independent prognostic factor for overall survival. Our results confirmed the existence of VM for the first time and revealed that VM is a strong independent prognostic factor for survival in patients with medulloblastoma.