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1.
Pathol Res Pract ; 216(2): 152785, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31889588

RESUMO

The relationship between integrin beta 4 (ITGB4) expression and laryngeal squamous cell carcinoma (LSCC) remains unclarified. The object of the present study was to explore the clinical significance and potential molecular mechanism of ITGB4 in LSCC. The protein level of ITGB4 was significantly higher in 46 LSCC patients than in 26 non-LSCC tissues detected by in-house immunohistochemistry. Consistently, ITGB4 mRNA level was also greatly upregulated based on microarray and RNA-seq data (standard mean difference, SMD = 1.62, 95 % CI: 1.23-2.00). And the area under curves (AUC) of summary receiver operator characteristic (SROC) was 0.87 (95 % CI: 0.84-0.90) based on 172 cases of LSCC and 59 cases of non-cancerous controls. Ninety genes were intersected by the ITGB4 related genes and LSCC differential expressed genes (DEGs) from all available microarray and RNA-seq datasets. Based on Gene Ontology (GO) analysis, the top terms of biological process (BP), cellular component (CC) and molecular function (MF) for the 90 ITGB4 related DEGs were extracellular matrix organization, basement membrane and extracellular matrix structural constituent, respectively. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that ITGB4 related DEGs mainly participated in the pathways of ECM-receptor interaction, Focal adhesion and Small cell lung cancer. Moreover, the Protein-Protein Interaction (PPI) network indicated that ITGA3, ITGA5, ITGB4, MET, LAMA3, and COL4A1 might be the core genes of LSCC development related to ITGB4. In conclusion, high ITGB4 expression may lead to the occurrence and development of LSCC via various signaling pathways.

2.
FASEB J ; 34(3): 4120-4133, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31953889

RESUMO

Hepatic stellate cells (HSCs) are the main effectors for various types of hepatic fibrosis, including Schistosome-induced hepatic fibrosis. Multiple inflammatory cytokines/chemokines, such as transforming growth factor-ß1 (TGF-ß1), activate HSCs, and contribute to the development of hepatic fibrosis. MicroRNAs regulate gene expression at the posttranscriptional level and are involved in regulation of inflammatory cytokine/chemokine synthesis. In this study, we showed that soluble egg antigen (SEA) stimulation and Schistosoma japonicum infection downregulate miR-27b expression and increase KH-type splicing regulatory protein (KSRP) mRNA and protein levels in vitro and in vivo. miR-27b regulates the stabilization of TGF-ß1 mRNA through targeting KSRP by interacting with their AU-rich elements in hepatocytes and non-parenchymal cells, which has an effect on the activation of HSCs. Importantly, our results have shown that either knockdown miR-27b or overexpression of KSRP attenuates S. japonicum-induced hepatic fibrosis in vivo. Therefore, our study highlights the crucial role of miR-27b and KSRP in the negative regulation of immune reactions in hepatocyte and non-parenchymal cells in response to SEA stimulation and S. japonicum infection. It reveals that manipulation of miR-27b or KSRP might be a useful strategy not only for treating Schistosome-induced hepatic fibrosis but also for curing hepatic fibrosis in general.

3.
Appl Microbiol Biotechnol ; 104(5): 2017-2028, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31930453

RESUMO

This paper focuses on the production of a high-affinity monoclonal antibody (mAb) that can efficiently detect and block purinergic ligand-gated ion channel 7 receptor (P2X7R). To achieve this goal, the extracellular domain of human P2X7R, P2X7R-ECD, was used as an immunogen for BALB/c mice, inducing them to produce spleen lymphocytes that were subsequently fused with myeloma cells. Screening of the resultant hybridoma clones resulted in the selection of one stable positive clone that produced a qualified mAb, named 4B3A4. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis demonstrated that the purity of the purified 4B3A4 mAb was above 85%, with prominent bands corresponding to molecular weights of 55 kDa (heavy chain) and 25 kDa (light chain), and the BCA assay showed that the concentration of the purified 4B3A4 mAb was 0.3 mg/mL. Western blot analysis revealed that the 4B3A4 mAb could specifically recognize and bind both P2X7R-ECD and the full-length P2X7R protein. Laser scanning confocal microscopy (LSCM) revealed that the 4B3A4 mAb specifically bound to P2X7R on the membrane of human peripheral blood mononuclear cells (PBMCs). P2X7R expression was significantly different between healthy individuals and people with certain cancers as determined by flow cytometry (FCM). In addition, the 4B3A4 mAb significantly reduced ATP-stimulated Ca2+ entry and YO-PRO-1 uptake, which indicated that the 4B3A4 mAb effectively blocked P2X7R activity. These data indicate that the 4B3A4 mAb can be further used as not only an antibody to detect cell surface P2X7R but also as a therapeutic antibody to target P2X7R-related signaling pathways.


Assuntos
Anticorpos Monoclonais/imunologia , Receptores Purinérgicos P2X7/imunologia , Animais , Anticorpos Monoclonais/química , Especificidade de Anticorpos , Benzoxazóis/metabolismo , Cálcio/metabolismo , Membrana Celular/metabolismo , Células Cultivadas , Feminino , Humanos , Imunoglobulina G/química , Imunoglobulina G/imunologia , Leucócitos Mononucleares/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Peso Molecular , Domínios Proteicos , Compostos de Quinolínio/metabolismo , Receptores Purinérgicos P2X7/química
4.
J Neurosurg ; : 1-9, 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31881545

RESUMO

OBJECTIVE: Chordoma shows poor patient prognosis because of its high recurrence rate. Even though many clinical factors and biomarkers are reported to be associated with prognosis, no prediction model has been applied clinically. Thus, the authors aim to derive and validate a prognostic nomogram to predict progression-free survival (PFS) of chordoma. METHODS: A total of 201 patients were randomly divided into a derivation group (151 cases) and a validation group (50 cases). The expression levels of biomarkers were quantified using tissue microarray analysis. A nomogram was established via univariate and multivariate Cox regression analysis in the derivation group. The predictive performance of the nomogram was then tested in the validation group. RESULTS: The mean follow-up interval was 57 months (range 26-107 months). One clinical factor and 3 biomarkers were confirmed to be associated with PFS, including degree of resection, E-cadherin, Ki-67, and VEGFA. The nomogram with these prognostic factors had areas under the receiver operating characteristic curve of 0.87 and 0.95 in the derivation group at 3 years and 5 years, respectively, compared with 0.87 and 0.84 in the validation group. Calibration and score-stratified survival curve were good in the derivation group and validation group, respectively. CONCLUSIONS: The established nomogram performs well for predicting the PFS of chordoma and for risk stratification, which could facilitate prognostic evaluation and follow-up.

5.
J Immunol ; 203(6): 1548-1559, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31383742

RESUMO

Long noncoding RNAs are important regulators of gene expression in innate immune responses. Antisense IL-7 (IL-7-AS) is a newly discovered long noncoding RNA in human and mouse that has been reported to regulate the expression of IL-6. However, the potential function of IL-7-AS in innate immune system is not fully understood. In this study, we found that the expression of IL-7-AS is primarily dependent on the NF-κB and MAPK signaling pathways in macrophages and intestinal epithelial cells. Functionally, IL-7-AS promotes the expression of several inflammatory genes, including CCL2, CCL5, CCL7, and IL-6, in cells in response to LPS. Specifically, IL-7-AS physically interacts with p300 to regulate histone acetylation levels around the promoter regions of these gene loci. Moreover, IL-7-AS and p300 complex modulate the assembly of SWI/SNF complex to the promoters. IL-7-AS regulates chemotaxis activity of monocytes to intestine epithelial cells with involvement of CCL2. Therefore, our data indicate a new promoting role for NF-κB/MAPK-responsive IL-7-AS in the transcriptional regulation of inflammatory genes in the innate immune system although modulation of histone acetylation around the promoters of related genes.

6.
World Neurosurg ; 129: e199-e206, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31125781

RESUMO

OBJECTIVE: We aimed to characterize the expression of transforming growth factor-α (TGF-α) and Ki-67 and to assess the relationship between TGF-α and Ki-67 expression and prognostic factors in skull base chordoma. METHODS: We retrospectively analyzed the data from 46 patients with skull base chordoma. The follow-up duration ranged from 1 to 168 months (mean, 74.1). The survival data were statistically analyzed using the Kaplan-Meier method and multivariate Cox regression analysis. The expression of TGF-α and Ki-67 were detected by immunohistochemical staining of paraffin-embedded patient tissue specimens. RESULTS: The total resection (TR) group had longer overall survival compared with the non-TR group (P = 0.042). The TR group also had longer progression-free survival (PFS) than did the non-TR group (P = 0.046). The group with a high Ki-67 labeling index (Ki-67LI) had shorter overall survival than did the group with a low Ki-67LI (P = 0.039). Also, the group with a high Ki-67LI had significantly shorter PFS than did the group with a low Ki-67LI (P = 0.016). Moreover, the group with high TGF-α expression had significantly shorter PFS compared with the group with low TGF-α expression (P = 0.005). CONCLUSIONS: Our results have shown that high levels of TGF-α and Ki-67 are associated with shorter PFS in patients with chordoma. We have confirmed the role of Ki-67 as a functional molecular marker of poor prognosis. We also identified TGF-α as a potential novel biomarker for predicting prognosis for patients with skull base chordoma.


Assuntos
Cordoma/mortalidade , Antígeno Ki-67/metabolismo , Neoplasias da Base do Crânio/mortalidade , Fator de Crescimento Transformador alfa/metabolismo , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Cordoma/metabolismo , Cordoma/patologia , Cordoma/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Neoplasias da Base do Crânio/metabolismo , Neoplasias da Base do Crânio/patologia , Neoplasias da Base do Crânio/cirurgia , Taxa de Sobrevida , Adulto Jovem
7.
Oncol Rep ; 41(1): 113-124, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30542712

RESUMO

Clinical non­functioning pituitary adenoma (NFPA) accounts for >30% of all pituitary adenomas, and the recurrence rate is notably high. The ability to predict tumour recurrence during initial surgery will aid in determining if adjunctive therapy is required to reduce recurrence. With the aim of developing a circular RNA (circRNA) signature to improve prognosis prediction in NFPA, the present study examined the circRNA expression profiles in 73 patients with NFPA from Beijing Tiantan Hospital using high­throughput RNA chip technology. The dataset was randomly separated into a training group and a test group using an R program. In the training group (n=37), a Cox proportional hazards regression model was used to analyse the genes associated with the recurrence and progression­free survival (PFS) of patients with NFPA. Meanwhile, a random survival forest algorithm, Kaplan­Meier and receiver operating characteristic curve (ROC) analyses were used to determine the multi­circRNA signature with the largest area under the ROC curve (AUROC) and verify its efficacy in the test group (n=36). In the training and test groups, the signatures of two circRNAs (hsa_circ_0000066 and hsa_circ_0069707) were specifically associated with the PFS of patients with NFPA (log­rank P<0.05). Furthermore, the two­circRNA signature had a high prediction accuracy for tumour recurrence, with an AUROC of 0.87 and 0.67 in the training and test groups, respectively; and the discriminative power of the signature was greater compared with that of age. The present study is the first to suggest a circRNA signature with a clinical application value for predicting recurrence/progression in patients with NFPA.


Assuntos
Adenoma/sangue , Recidiva Local de Neoplasia/diagnóstico , Neoplasias Hipofisárias/sangue , RNA/sangue , Adenoma/mortalidade , Adenoma/patologia , Adulto , Idoso , Progressão da Doença , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Neoplasias Hipofisárias/mortalidade , Neoplasias Hipofisárias/patologia , Valor Preditivo dos Testes , Prognóstico , Intervalo Livre de Progressão , Curva ROC , Análise de Sobrevida
8.
Sensors (Basel) ; 18(11)2018 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-30428617

RESUMO

With the recently explosive growth of deep learning, automatic modulation recognition has undergone rapid development. Most of the newly proposed methods are dependent on large numbers of labeled samples. We are committed to using fewer labeled samples to perform automatic modulation recognition in the cognitive radio domain. Here, a semi-supervised learning method based on adversarial training is proposed which is called signal classifier generative adversarial network. Most of the prior methods based on this technology involve computer vision applications. However, we improve the existing network structure of a generative adversarial network by adding the encoder network and a signal spatial transform module, allowing our framework to address radio signal processing tasks more efficiently. These two technical improvements effectively avoid nonconvergence and mode collapse problems caused by the complexity of the radio signals. The results of simulations show that compared with well-known deep learning methods, our method improves the classification accuracy on a synthetic radio frequency dataset by 0.1% to 12%. In addition, we verify the advantages of our method in a semi-supervised scenario and obtain a significant increase in accuracy compared with traditional semi-supervised learning methods.

9.
Sensors (Basel) ; 18(10)2018 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-30250004

RESUMO

Reliability and energy efficiency are two key considerations when designing a compressive sensing (CS)-based data-gathering scheme. Most researchers assume there is no packets loss, thus, they focus only on reducing the energy consumption in wireless sensor networks (WSNs) while setting reliability concerns aside. To balance the performance⁻energy trade-off in lossy WSNs, a distributed data storage (DDS) and gathering scheme based on CS (CS-DDSG) is introduced, which combines CS and DDS. CS-DDSG utilizes broadcast properties to resist the impact of packet loss rates. Neighboring nodes receive packets with process constraints imposed to decrease the volume of both transmissions and receptions. The mobile sink randomly queries nodes and constructs a measurement matrix based on received data with the purpose of avoiding measuring the lossy nodes. Additionally, we demonstrate how this measurement matrix satisfies the restricted isometry property. To analyze the efficiency of the proposed scheme, an expression that reflects the total number of transmissions and receptions is formulated via random geometric graph theory. Simulation results indicate that our scheme achieves high precision for unreliable links and reduces the number of transmissions, receptions and fusions. Thus, our proposed CS-DDSG approach effectively balances energy consumption and reconstruction accuracy.

10.
Sensors (Basel) ; 18(9)2018 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-30227685

RESUMO

Mobile Edge Computing (MEC) has evolved into a promising technology that can relieve computing pressure on wireless devices (WDs) in the Internet of Things (IoT) by offloading computation tasks to the MEC server. Resource management and allocation are challenging because of the unpredictability of task arrival, wireless channel status and energy consumption. To address such a challenge, in this paper, we provide an energy-efficient joint resource management and allocation (ECM-RMA) policy to reduce time-averaged energy consumption in a multi-user multi-task MEC system with hybrid energy harvested WDs. We first formulate the time-averaged energy consumption minimization problem while the MEC system satisfied both the data queue stability constraint and energy queue stability constraint. To solve the stochastic optimization problem, we turn the problem into two deterministic sub-problems, which can be easily solved by convex optimization technique and linear programming technique. Correspondingly, we propose the ECM-RMA algorithm that does not require priori knowledge of stochastic processes such as channel states, data arrivals and green energy harvesting. Most importantly, the proposed algorithm achieves the energy consumption-delay trade-off as [ O ( 1 / V ) , O ( V ) ] . V, as a non-negative weight, which can effectively control the energy consumption-delay performance. Finally, simulation results verify the correctness of the theoretical analysis and the effectiveness of the proposed algorithm.

11.
World Neurosurg ; 115: e146-e151, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29649649

RESUMO

OBJECTIVE: To explore molecular markers of radiosensitivity and prognostic factors in patients with clival chordomas. METHODS: Retrospective review was performed of 35 patients. Mean follow-up interval was 66.37 months (range, 29-106 months). Kaplan-Meier method was used for survival analysis. Immunohistochemical staining was used to detect expression levels of extracellular signal-regulated kinase (ERK) and 15-hydroxyprostaglandin dehydrogenase (HPGD). RESULTS: Total resection was achieved in 12 cases, subtotal resection was achieved in 12 cases, and partial resection was achieved in 11 cases. Radiation-sensitive group comprised 17 cases, and radiation-resistant (RR) group comprised 18 cases. Five-year progression-free survival (PFS) rates in total resection and nontotal resection groups were 46.3% and 10.1%, respectively (P = 0.005). Mean H-scores of ERK in radiation-resistant and radiation-sensitive groups were 110.38 and 82.98, respectively (P = 0.043). Mean H-scores of HPGD in radiation-resistant and radiation-sensitive groups were 178.62 and 203.47, respectively (P = 0.031). Mean PFS in low ERK expression group (58.61 months) was significantly longer than mean PFS in high ERK expression group (24.94 months) (P = 0.022). Mean PFS in high HPGD expression group (39.54 months) was significantly longer than mean PFS in low HPGD expression group (9.5 months) (P = 0.013). CONCLUSIONS: Radical resection with protection of important structures is the most effective treatment of clival chordomas. High HPGD expression and low ERK expression were associated with radiation sensitivity and better prognosis. HPGD and ERK can be used as biomarkers to predict prognosis and guide treatment.


Assuntos
Cordoma/diagnóstico , Cordoma/radioterapia , MAP Quinases Reguladas por Sinal Extracelular/biossíntese , Hidroxiprostaglandina Desidrogenases/biossíntese , Neoplasias da Base do Crânio/diagnóstico , Neoplasias da Base do Crânio/radioterapia , Adolescente , Adulto , Idoso , Cordoma/enzimologia , Fossa Craniana Posterior , MAP Quinases Reguladas por Sinal Extracelular/genética , Seguimentos , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Hidroxiprostaglandina Desidrogenases/genética , Masculino , Pessoa de Meia-Idade , Prognóstico , Radiocirurgia/métodos , Estudos Retrospectivos , Neoplasias da Base do Crânio/enzimologia , Adulto Jovem
12.
J Neurosurg ; 129(6): 1429-1437, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-29303447

RESUMO

OBJECTIVEIn this study, the authors' aim was to research clinical features and prognostic factors in patients harboring clival chordomas and explore the relationship between platelet-derived growth factor receptor-ß (PDGFR-ß) expression and tumor invasion and prognosis of clival chordoma.METHODSA total of 242 patients were retrospectively analyzed. Clinical information, including extent of resection, Al-Mefty classification, postoperative complications, and postoperative radiotherapy, was reviewed. Kaplan-Meier analysis was used to estimate survival time. Immunohistochemical analysis, quantitative reverse transcription polymerase chain reaction, and Western blotting were used to measure the expression level of proteins or mRNA. Transwell assaying was performed to measure the invasive ability of the tumor cells.RESULTSAccording to the Al-Mefty classification, there were 37, 112, and 93 type I, II, and III tumors, respectively. Gross-total resection (GTR) was achieved in 86 cases (35.5%), subtotal resection (STR) in 63 cases (26.0%), and partial resection (PR) in 93 cases (38.4%). The 5-year progression-free survival (PFS) and overall survival (OS) rates in the GTR group were significantly higher than those in the non-total resection (NTR; i.e., STR and PR) group (p < 0.001). The 5-year PFS and OS rates for patients with type I tumors were significantly higher than those for patients harboring types II and III tumors (p < 0.001). In the NTR group, the median PFS and OS of patients with lower PDGFR-ß expression were significantly longer than those of patients with higher PDGFR-ß expression. Reduction of PDGFR-ß suppressed the invasion ability of cells in vitro. In addition, reduction of PDGFR-ß can obviously downregulate the expression levels of mammalian target of rapamycin (mTOR) or phospho-mTOR.CONCLUSIONSExtent of resection, Al-Mefty classification, primary tumor, postoperative radiotherapy, and PDGFR-ß expression level are valuable prognostic factors in patients with clival chordomas. PDGFR-ß could regulate invasion through the mTOR pathway in clival chordoma cells.


Assuntos
Cordoma/cirurgia , Fossa Craniana Posterior/cirurgia , Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo , Neoplasias da Base do Crânio/cirurgia , Adolescente , Adulto , Idoso , Linhagem Celular Tumoral , Criança , Cordoma/metabolismo , Cordoma/mortalidade , Fossa Craniana Posterior/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Neoplasias da Base do Crânio/metabolismo , Neoplasias da Base do Crânio/mortalidade , Taxa de Sobrevida , Adulto Jovem
13.
J Neurooncol ; 137(1): 139-146, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29222701

RESUMO

The current study aimed to characterize SNF5 expression and investigate the relationship between SNF5 and clinicopathological features in skull base chordoma. 48 patients diagnosed with skull base chordoma were enrolled in this study. Tissue microarray and immunohistochemistry were performed to evaluate the expression of SNF5 in skull base chordoma. Kaplan-Meier survival analysis was used to assess survival. Multivariable Cox regression analysis was used to identify risk factors affecting patient survival. The H-scores for cytoplasmic SNF5 ranged from 124.47 to 254.52. Low expression of SNF5 was correlated with shorter overall survival (OS) (p = 0.021). Patients with age > 55 years old had shorter progression free survival (PFS) and OS times than patients whose age ≤ 55 years old (p = 0.005 and 0.003, respectively). The gross total resection group showed longer PFS than the non-gross total resection group (p = 0.024). Females showed shorter PFS times than males (p = 0.033). Multivariable Cox regression analysis showed that age, extent of resection and sex were independent prognostic factors for PFS (p = 0.010, 0.013 and 0.042, respectively). Age was an independent prognostic factor for OS (p = 0.010). Our study indicate that low expression of SNF5 is associated with poor prognosis in skull base chordoma.


Assuntos
Cordoma/diagnóstico , Cordoma/metabolismo , Proteína SMARCB1/metabolismo , Neoplasias da Base do Crânio/diagnóstico , Neoplasias da Base do Crânio/metabolismo , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Adulto Jovem
14.
J Immunol ; 199(10): 3571-3582, 2017 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-28993514

RESUMO

Long noncoding RNAs, a newly identified class of noncoding RNAs, are important regulators of gene expression in innate immunity. We report in this study that the transcription of FIRRE, a conserved long noncoding RNA between humans and mice, is controlled by NF-κB signaling in macrophages and intestinal epithelial cells. Functionally, FIRRE appears to positively regulate the expression of several inflammatory genes in macrophages or intestinal epithelial cells in response to LPS stimulation via posttranscriptional mechanisms. Specifically, FIRRE physically interacts with heterogeneous nuclear ribonucleoproteins U, regulating the stability of mRNAs of selected inflammatory genes through targeting the AU-rich elements of their mRNAs in cells following LPS stimulation. Therefore, our data indicate a new regulatory role for NF-κB-responsive FIRRE in the posttranscriptional regulation of inflammatory genes in the innate immune system.


Assuntos
Sequência Conservada/genética , Inflamação/genética , Mucosa Intestinal/imunologia , Macrófagos/imunologia , NF-kappa B/metabolismo , RNA Longo não Codificante/genética , Elementos de Resposta/genética , Animais , Regulação da Expressão Gênica , Ribonucleoproteínas Nucleares Heterogêneas/metabolismo , Humanos , Imunidade Inata , Camundongos , RNA Longo não Codificante/metabolismo , RNA Interferente Pequeno/genética , Células U937
17.
World Neurosurg ; 98: 323-328, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27838423

RESUMO

OBJECTIVE: Chordomas in children and adolescents are rare, and minimal published information is available. Our aim was to research clinical features and prognostic factors associated with clival chordomas in younger patients. METHODS: The study included 25 patients (10 males and 15 females). Average follow-up time was 42.95 months (range, 2-108 months). Kaplan-Meier analysis was used to determine overall survival (OS) and progression-free survival. Pearson correlation was used to perform correlation analysis. Immunohistochemistry was used to detect Ki-67, cytokeratin 8 (CK8), platelet-derived growth factor receptor-ß, and brachyury expression levels. RESULTS: Average age (± SD) of patients was 14.44 (3.44) years. Total resection was achieved in 5 cases, and nontotal resection was achieved in 20 cases. Average OS of patients with Karnofsky performance scale score ≥90 and patients in the total resection group was significantly longer compared with OS of patients with Karnofsky performance scale score <90 (P = 0.041) and patients in the nontotal resection group (P = 0.0497). Patients with lower Ki-67 expression levels had longer OS (P = 0.0207). Progression-free survival of patients with lower CK8 expression levels was significantly longer compared with patients with higher CK8 levels (P = 0.008). Expression levels of platelet-derived growth factor receptor-ß were significantly correlated with expression levels of brachyury (P = 0.016). CONCLUSIONS: In children and adolescents with clival chordomas, higher preoperative Karnofsky performance scale score, total resection, and lower levels of Ki-67 and CK8 expression are favorable prognostic factors. Platelet-derived growth factor receptor-ß may play a role in tumorigenesis and epithelial-mesenchymal transition of clival chordomas.


Assuntos
Cordoma/diagnóstico por imagem , Cordoma/cirurgia , Neoplasias da Base do Crânio/diagnóstico por imagem , Neoplasias da Base do Crânio/cirurgia , Adolescente , Criança , Fossa Craniana Posterior/diagnóstico por imagem , Fossa Craniana Posterior/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Prognóstico , Adulto Jovem
18.
World Neurosurg ; 99: 282-287, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27916725

RESUMO

OBJECTIVE: Skull base chordomas are clinically malignant because of the difficulty of total removal and the high recurrence rate. Because the disease-free survival after surgery is currently unpredictable, there is a need for new parameters, obtained from histologic analyses of the resection specimen, that allows a risk stratification of patients with chordoma. METHODS: In recent years, electron microscopic diagnoses were introduced into the clinical practice for the diagnosis of chordoma in our department. Clinical outcomes and electron microscopic features were retrospectively reviewed in the study. The electron micrograph shows that clival chordoma can be divided into cell-dense type (CDT) and matrix-rich type (MRT). Of all the patients with chordoma, complete data from 27 patients were obtained. There were 12 patients in the CDT group and 15 patients in the MRT group. The paraffin-embedded tissue samples were stained with Ki-67 antibody. The prognostic values of electron microscopic classification were compared between the 2 groups. RESULTS: There were no statistical differences in the gender (P = 0.704) and age distribution (P = 0.243) between the 2 groups. There was also no statistical difference concerning the constitution of primitive tumors and recurrent tumors between the 2 groups (P = 0.706). The CDT group had a higher mortality rate than the MRT group (P = 0.037). The tumors in the CDT group were prone to recurrence and the need for reoperation within 1 year after surgery, which is statistically different from that in the MRT group (P < 0.001). Chordoma tumors of 23 patients (85.2%) stained positive for Ki-67. CDT chordomas had a higher Ki-67 proliferation index than the MRT chordomas (P = 0.013). CONCLUSIONS: The present study demonstrates the utility of the ultrastructural features in the prognostic outcome of patients with chordoma. According to the ultrastructures of chordomas, they can be divided into CDT and MRT. CDT chordoma cells have a more aggressive proliferative ability. Patients with CDT have a poor prognostic factor in clival chordoma, which has a higher risk of recurrence and a shorter survival.


Assuntos
Cordoma/mortalidade , Cordoma/patologia , Microscopia Eletrônica/estatística & dados numéricos , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Neoplasias da Base do Crânio/mortalidade , Neoplasias da Base do Crânio/patologia , Adulto , Idoso , China/epidemiologia , Cordoma/ultraestrutura , Fossa Craniana Posterior/patologia , Fossa Craniana Posterior/ultraestrutura , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/ultraestrutura , Prevalência , Prognóstico , Reprodutibilidade dos Testes , Fatores de Risco , Sensibilidade e Especificidade , Neoplasias da Base do Crânio/ultraestrutura , Análise de Sobrevida
19.
J Exp Clin Cancer Res ; 35(1): 152, 2016 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-27669982

RESUMO

BACKGROUND: Transducin-like enhancer of Split3 (TLE3) serves as a transcriptional corepressor during cell differentiation and shows multiple roles in different kinds of cancers. Recently, TLE3 together with many other genes involved in Wnt/ß-catenin pathway were detected hyper-methylated in colorectal cancer (CRC). However, the potential role and the underlying mechanism of TLE3 in CRC progression remain scarce. METHODS: Gene expression profiles were analyzed in The Cancer Genome Atlas (TCGA) microarray dataset of 41 normal colorectal intestine tissues and 465 CRC tissues. Western blot and Real-time Quantitative PCR (RT-qPCR) were respectively performed to detect protein and mRNA expression in 8 pairs of CRC tissue and matched adjacent normal mucosa. Immunohistochemistry (IHC) was conducted to evaluate TLE3 protein expression in 105 paraffin-embedded, archived human CRC tissues from patients, whose survival data were analyzed with Kaplan-Meier method. In vitro experiments including MTT assay, colony formation assay, and soft agar formation assay were used to investigate the effects of TLE3 on CRC cell growth and proliferation. Additionally, subcutaneous tumorigenesis assay was performed in nude mice to confirm the effects of TLE3 in vivo. Furthermore, gene set enrichment analysis (GSEA) was run to explore potential mechanism of TLE3 in CRC, and then we measured the distribution of CRC cell cycle phases and apoptosis by flow cytometry, as well as the impacts of TLE3 on MAPK and AKT signaling pathways by Western blot and RT-qPCR. RESULTS: TLE3 was significantly down-regulated in 465 CRC tissues compared with 41 normal tissues. Both protein and mRNA expressions of TLE3 were down-regulated in CRC compared with matched adjacent normal mucosa. Lower expression of TLE3 was significantly associated with poorer survival of patients with CRC. Besides, knock down of TLE3 promoted CRC cell growth and proliferation, while overexpression of TLE3 showed suppressive effects. Furthermore, overexpression of TLE3 caused G1-S phase transition arrest, inhibition of MAPK and AKT pathways, and up-regulation of p21Cip1/WAF1 and p27Kip1. CONCLUSION: This study indicated that TLE3 repressed CRC proliferation partly through inhibition of MAPK and AKT signaling pathways, suggesting the possibility of TLE3 as a biomarker for CRC prognosis.

20.
J Cancer Res Ther ; 11 Suppl 2: C212-5, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26506879

RESUMO

OBJECTIVE: To identify a specific hypermethylated molecular biomarker for human malignant glioblastoma prognosis. MATERIALS AND METHODS: Genome-wide methylation profiling was performed on 33 tumors and 3 normal glioblastoma samples using the Infinium HumanMethylation450 microarray. Cluster analysis was carried out in these samples according to the differentiated methylated genes. DNA methylation of selected significant candidates was subsequently validated to analyze the association of methylation status of these genes with overall survival as well as gene expression. RESULTS: We found 217 hypermethylated CpG sites located in 210 respective genes with significant differences in short- and long-term survival (STS and LTS) samples (P < 0.01). Cluster analysis revealed fine clustering of genes with LTS and STS. Of these, we selected 10 most hypermethylated genes, including IL11, RRAD, MS4A6A, SNAPC2, ALDH1A3, ADCY1, MMS19L, NDUFB8, POMC, and THSD4, to perform cluster analysis. It came out with the same fine classification and with survival time of these patients. The top ranking genes were further examined to compare their methylation status with the overall survival rate of patients, as well as with gene expression levels. CONCLUSION: We obtained a featured global profiling of DNA methylation in glioblastoma. Our findings strongly indicate that epigenetic silencing of IL11, RRAD, MS4A6A, SNAPC2, and ALDH1A3 are common events in glioblastoma which could be used as novel biomarkers for the prognosis of glioblastoma.


Assuntos
Metilação de DNA , Epigênese Genética , Epigenômica , Estudo de Associação Genômica Ampla , Glioblastoma/genética , Glioblastoma/mortalidade , Análise por Conglomerados , Ilhas de CpG , Epigenômica/métodos , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Estudo de Associação Genômica Ampla/métodos , Humanos , Masculino , Prognóstico , Reprodutibilidade dos Testes
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