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1.
Micromachines (Basel) ; 14(8)2023 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-37630160

RESUMEN

A taste sensor with global selectivity can be used to discriminate taste of foods and provide evaluations. Interfaces that could interact with broad food ingredients are beneficial for data collection. Here, we prepared electrochemically reduced graphene oxide (ERGO)-modified interdigital electrodes. The interfaces of modified electrodes showed good sensitivity towards cooking condiments in mixed multi-ingredients solutions under electrochemical impedance spectroscopy (EIS). A database of EIS of cooking condiments was established. Based on the principal component analysis (PCA), subsets of three taste dimensions were classified, which could distinguish an unknown dish from a standard dish. Further, we demonstrated the effectiveness of the electrodes on a typical dish of scrambled eggs with tomato. Our kind of electronic tongue did not measure the quantitation of each ingredient, instead relying on the database and classification algorithm. This method is facile and offers a universal approach to simultaneously identifying multiple ingredients.

2.
J Colloid Interface Sci ; 650(Pt A): 322-329, 2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-37413866

RESUMEN

Aqueous zinc-ion batteries (AZIB) have several advantages such as low cost, large theoretical capacity and good safety. However, the development of polyaniline (PANI) cathode materials has been limited by slow diffusion kinetics. Herein, proton-self-doped polyaniline@carbon cloth (CC) (PANI@CC) was prepared via in-situ polymerization, where polyaniline was deposited on an activated carbon cloth. The PANI@CC cathode exhibits a high specific capacity of 234.3 mA h g-1 at 0.5 A g-1, and excellent rate performance, delivering a capacity of 143 mA h g-1 at 10 A g-1. Furthermore, the reversible redox conversion during the charge-discharge process was studied using ex-situ X-ray photoelectron spectroscopy (XPS) and ex-situ Raman spectra. The results show that the excellent performance of the PANI@CC battery can be attributed to the formation of a conductive network between the carbon cloth and polyaniline. Also, a mixing mechanism involving insertion/extraction of Zn2+/H+ and a double-ion process is proposed. PANI@CC electrode is a novel idea for developing high-performance batteries.

3.
J Cancer ; 14(8): 1272-1281, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37283795

RESUMEN

Background: A less effective nomogram for patients with intermediate-stage hepatocellular carcinoma (HCC) to predict overall survival (OS) is available. This study aimed to investigate the role of age-male-albumin-bilirubin-platelet (aMAP) scores in the prognosis of patients with intermediate-stage HCC and develop an aMAP score-based nomogram to predict OS. Methods: Data on newly diagnosed intermediate-stage patients with HCC at Sun Yat-sen University Cancer Center between January 2007 and May 2012 were retrospectively collected. Independent risk factors affecting prognosis were selected by multivariate analyses. The optimal cut-off value for the aMAP score was determined using X-tile. The survival prognostic models were presented by the nomogram. Results: For the 875 patients with intermediate-stage HCC included, the median OS was 22.2 months (95% CI 19.6-25.1). Patients were classified into three groups by X-tile plots (aMAP score < 49.42; 49.42 ≤ aMAP score < 56; aMAP score ≥ 56). Alpha-fetoprotein, lactate dehydrogenase, aMAP score, diameter of main tumor, number of intrahepatic lesions, and treatment regimen were independent risk factors for prognosis. A predicted model was constructed with a C-index of 0.70 (95% CI: 0.68-0.72) in the training goup, and its 1-, 3-, and 5-year area under the receiver operating curve were: 0.75, 0.73, and 0.72. The validation group of the C-index is 0.82. Calibration graphs showed good consistency between the actual and predicted survival rates. The decision curve analysis suggested the clinical utility of the model, which may help clinicians guide clinical decision-making. Conclusion: The aMAP score was an independent risk factor for intermediate-stage HCC. The aMAP score-based nomogram has good discrimination, calibration, and clinical utility.

4.
Front Oncol ; 12: 827811, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35646690

RESUMEN

Advanced adenoma (AA) holds a significantly increased risk for progression to colorectal cancer (CRC), and we developed a noninvasive DNA methylation prediction model to monitor the risk of AA progression to CRC. We analyzed the differential methylation markers between 53 normal mucosa and 138 CRC tissues, as well as those in cfDNA (cell-free DNA) between 59 AA and 68 early-stage CRC patients. We screened the overlapping markers between tissue DNA and cfDNA for model variables and optimized the selected variables. Then, we established a cfDNA methylation prediction model (SDMBP model) containing seven methylation markers that can effectively discriminate early-stage CRC and AA in the training and validation cohorts, and the AUC (area under the curve) reached 0.979 and 0.918, respectively. Our model also reached high precision (AUC=0.938) in detecting advanced CRC (stage III/IV) and presented better performance than serum CEA and CA199 in screening CRC. The cd-score of the SDMBP model could also robustly predict the TNM stage of CRC. Overall, our SDMBP model can monitor the malignant progression from AA to CRC, and may provide a noninvasive monitoring method for high-risk populations with AA.

5.
Front Robot AI ; 8: 724138, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34765648

RESUMEN

Dynamic quadrupedal locomotion over rough terrains reveals remarkable progress over the last few decades. Small-scale quadruped robots are adequately flexible and adaptable to traverse uneven terrains along the sagittal direction, such as slopes and stairs. To accomplish autonomous locomotion navigation in complex environments, spinning is a fundamental yet indispensable functionality for legged robots. However, spinning behaviors of quadruped robots on uneven terrain often exhibit position drifts. Motivated by this problem, this study presents an algorithmic method to enable accurate spinning motions over uneven terrain and constrain the spinning radius of the center of mass (CoM) to be bounded within a small range to minimize the drift risks. A modified spherical foot kinematics representation is proposed to improve the foot kinematic model and rolling dynamics of the quadruped during locomotion. A CoM planner is proposed to generate a stable spinning motion based on projected stability margins. Accurate motion tracking is accomplished with linear quadratic regulator (LQR) to bind the position drift during the spinning movement. Experiments are conducted on a small-scale quadruped robot and the effectiveness of the proposed method is verified on versatile terrains including flat ground, stairs, and slopes.

6.
Micromachines (Basel) ; 12(7)2021 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-34357200

RESUMEN

The labyrinth screw pump is a new type of low-flow rotor pump with a simple structure and good sealing performance. It is suitable for the transport of high-viscosity, high-gas-content, and particle-containing media. In this study, a rectangular labyrinth screw pump was used as the research object. The effect of the medium viscosity on the performance of the labyrinth pump was studied through numerical simulations, and the correctness of the simulation method was verified using existing test data. The efficiency and head of the labyrinth screw pump were selected as the optimization objectives, and the pump structural parameters were selected as the optimization parameters. A structural optimization model of the labyrinth screw pump based on response surface theory was established. The structural parameters of the labyrinth pump were reasonably simplified through size correlations, and then parameter sensitivity analysis was performed to determine the important structural parameters that needed to be optimized. The OSFD (optimized space-filling design) was used to combine the optimized parameters and generate the sample space. The response surface theory was combined with a neural network prediction model and a multi-objective genetic algorithm to perform optimization calculations. The results showed that there was an interactive influence between the structural parameters of the stator and rotor of the labyrinth screw pump. Compared with the original model, the optimized model pump had an efficiency increase of 13.55% and a lift increase of 19.53% when conveying a medium with a viscosity of 133 cp.

7.
Surg Endosc ; 34(9): 3827-3832, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-31617089

RESUMEN

BACKGROUND AND AIM: Although successful endoscopic resection of gastric subepithelial tumors (SETs) originating from the muscularis propria (MP) layer has been frequently reported, it requires a relatively complicated technique and has a high perforation rate. In this retrospective study, we evaluated the efficacy and safety of the snare-assisted endoscopic resection (SAER) method which is performed using a snare and insulated-tip (IT) knife via a single-channel endoscope to reduce the perforation rate. METHODS: In this study, fifty-six patients with gastric SETs originating from the MP layer treated by the SAER method at three institutions between July 2017 and December 2017 were reviewed. The procedure involved multiple steps as shown in Fig. 2. Data were obtained on demographics, SET features, histopathological diagnoses, procedure time, en bloc resection rate, R0 resection (negative margins) status, and adverse events. RESULTS: Endoscopic resection was successfully performed in all patients. The median overall procedure time was 43.5 min (range 26-106 min). The mean size of resected specimens was 19.73 mm (range 10-33 mm). The overall rate of en bloc resection was 96.4% (54/56). In addition, the perforation rate was 7.1% (4/56), and defects in the stomach wall were very small and easily closed using metallic clips. No postprocedural bleeding occurred in any case. CONCLUSIONS: The SAER method is an effective, safe, less costly technique for the removal of some gastric SETs originating from the MP layer with an appropriate size.


Asunto(s)
Mucosa Gástrica/cirugía , Gastroscopía/métodos , Estadificación de Neoplasias , Neoplasias Gástricas/cirugía , Adulto , Anciano , Femenino , Mucosa Gástrica/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Neoplasias Gástricas/diagnóstico , Resultado del Tratamiento
8.
Nat Nanotechnol ; 12(5): 434-440, 2017 05.
Artículo en Inglés | MEDLINE | ID: mdl-28369045

RESUMEN

The clean-up of viscous crude-oil spills is a global challenge. Hydrophobic and oleophilic oil sorbents have been demonstrated as promising candidates for oil-spill remediation. However, the sorption speeds of these oil sorbents for viscous crude oil are rather limited. Herein we report a Joule-heated graphene-wrapped sponge (GWS) to clean-up viscous crude oil at a high sorption speed. The Joule heat of the GWS reduced in situ the viscosity of the crude oil, which prominently increased the oil-diffusion coefficient in the pores of the GWS and thus speeded up the oil-sorption rate. The oil-sorption time was reduced by 94.6% compared with that of non-heated GWS. Besides, the oil-recovery speed was increased because of the viscosity decrease of crude oil. This in situ Joule self-heated sorbent design will promote the practical application of hydrophobic and oleophilic oil sorbents in the clean-up of viscous crude-oil spills.

9.
Adv Mater ; 28(47): 10459-10490, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27731513

RESUMEN

Oil sorbents play a very important part in the remediation processes of oil spills. To enhance the oil-sorption properties and simplify the oil-recovery process, various advanced oil sorbents and oil-collecting devices based on them have been proposed recently. Here, we firstly discuss the design considerations for the fabrication of oil sorbents and describe recently developed oil sorbents based on modification strategy. Then, recent advances regarding oil sorbents mainly based on carbon materials and swellable oleophilic polymers are also presented. Subsequently, some additional properties are emphasized, which are required by oil sorbents to cope with oil spills under extreme conditions or to facilitate the oil-collection processes. Furthermore, some oil-collection devices based on oil sorbents that have been developed recently are shown. Finally, an outlook and challenges for the next generation of oil-spill-remediation technology based on oil-sorbents materials are given.

10.
Chem Sci ; 7(7): 4276-4283, 2016 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-30155074

RESUMEN

Two-dimensional inorganic nanomaterials have drawn much attention due to their excellent properties and wide applications associated with unique 2D structures. However, an efficient and versatile chemical synthesis method using ambient conditions for 2D nanomaterials, especially with secondary structures (e.g. mesopores), has still not been reported. Herein, we report a versatile method to synthesize a family of ultrathin and mesoporous nanosheets of metal selenides based on a precursor so-called "red Se remaining Zn" (RSRZ). The principle of our synthesis is based on a template-assisted chemical transformation process via acidification of inorganic-organic hybrid ZnSe(DETA)0.5 nanosheets (DETA: diethylenetriamine). An appropriate amount of acid was added into an aqueous dispersion of ZnSe(DETA)0.5 nanosheets under air for activation. The acidification induced chemical transformation mechanism was studied by tracking the acidification process. This acid controlled reactivity of lamellar hybrids allows it to be possible to capture the highly reactive intermediates, which will provide a new platform for the synthesis of various mesoporous metal selenides.

11.
Adv Mater ; 28(4): 722-8, 2016 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-26618615

RESUMEN

A stretchable and multiple-force-sensitive electronic fabric based on stretchable coaxial sensor electrodes is fabricated for artificial-skin application. This electronic fabric, with only one kind of sensor unit, can simultaneously map and quantify the mechanical stresses induced by normal pressure, lateral strain, and flexion.


Asunto(s)
Piel Artificial , Electrodos , Electrónica , Nanocables/química , Poliuretanos/química , Povidona/química , Presión , Plata/química
12.
Biosens Bioelectron ; 63: 371-378, 2015 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-25127471

RESUMEN

Dielectrophoresis (DEP), the induced motion of polarizable particles in a non-uniform electric field, has been proven as a perfect candidate to transport, accumulate, separate and characterize micro-/nano-scale bioparticles in microfluidic systems. However, conventional fabrication technologies are complex, time-consuming and relatively expensive, leading to low throughput of the DEP-based systems. In this paper, we report a novel microfluidic alternating current DEP (AC-DEP) chip fabricated via inexpensive screen printing method. The innovation of our work consists in the extreme simplicity of the fabrication procedure, i.e., the main components, including electrodes and channels, were constructed by layer-by-layer screen printing process, which is especially suitable for high-throughput mass production. Carbon paste, instead of metals, was used to print interdigitated electrodes with semi-3D structure which not only reduces dramatically the chip cost but also increases particle trapping efficiency. To test the chip performance, yeast cells, as model cells, were trapped and separated from a mixed suspension with PS microspheres. Our results show that high capture rate and separation efficiency can be achieved under optimized conditions.


Asunto(s)
Técnicas Biosensibles/métodos , Separación Celular/métodos , Electroforesis/métodos , Técnicas Analíticas Microfluídicas/métodos , Carbono/química , Electrodos , Nanoestructuras/química , Impresión
13.
PLoS One ; 9(7): e103882, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25078779

RESUMEN

BACKGROUND: Activating transcription factor 4 (ATF4) is a stress response gene that is involved in homeostasis and cellular protection. However, its expression and function in esophageal squamous cell carcinoma (ESCC) remains unknown. In this study, we aimed to determine the clinicopathologic significance of ATF4 in ESCC and its potential role in ESCC invasion and metastasis. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrated that ATF4 overexpression is correlated with multiple malignant characteristics and indicates poor prognosis in ESCC patients. ATF4 expression was an independent factor that affected the overall survival of patients with ESCC after surgical resection. ATF4 promoted cell invasion and metastasis by promoting matrix metalloproteinase (MMP)-2 and MMP-7 expression, while its silencing significantly attenuated these activities both in vitro and in vivo. CONCLUSIONS/SIGNIFICANCE: We report that ATF4 is a potential biomarker for ESCC prognosis and that its dysregulation may play a key role in the regulation of invasion and metastasis in ESCC cells. The targeting of ATF4 may provide a new strategy for blocking ESCC metastasis.


Asunto(s)
Factor de Transcripción Activador 4/fisiología , Carcinoma de Células Escamosas/metabolismo , Neoplasias Esofágicas/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Pulmonares/metabolismo , Anciano , Animales , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/secundario , Línea Celular Tumoral , Movimiento Celular , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/secundario , Masculino , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 7 de la Matriz/metabolismo , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Análisis Multivariante , Invasividad Neoplásica , Trasplante de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales
14.
Cancer Lett ; 354(1): 142-52, 2014 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-25130172

RESUMEN

Multidrug resistance (MDR) is a major challenge to the clinical treatment of esophageal cancer. The stress response gene activating transcription factor 4 (ATF4) is involved in homeostasis and cellular protection. However, relatively little is known about the expression and function of ATF4 in esophageal squamous cell carcinoma (ESCC) MDR. In this study, we investigate the potential role and mechanisms of ATF4 in ESCC MDR. We demonstrated that overexpression of ATF4 promotes the MDR phenotype in ESCC cells, while depletion of ATF4 in the MDR ESCC cell line induces drug re-sensitization. We also demonstrated that ATF4 transactivates STAT3 expression by directly binding to the signal transducers and activators of transcription 3 (STAT3) promoter, resulting in MDR in ESCC cells. Significantly, inhibition of STAT3 by small interfering RNA (siRNA) or a selective inhibitor (JSI-124) reintroduces therapeutic sensitivity. In addition, increased Bcl-2, survivin, and MRP1 expression levels were observed in ATF4-overexpressing cells. In conclusion, ATF4 may promote MDR in ESCC cells through the up-regulation of STAT3 expression, and thus is an attractive therapeutic target to combat therapeutic resistance in ESCC.


Asunto(s)
Factor de Transcripción Activador 4/metabolismo , Carcinoma de Células Escamosas/metabolismo , Resistencia a Múltiples Medicamentos , Resistencia a Antineoplásicos , Neoplasias Esofágicas/metabolismo , Factor de Transcripción STAT3/metabolismo , Apoptosis , Carcinogénesis , Caspasa 3/metabolismo , Línea Celular Tumoral , Humanos , Proteínas Inhibidoras de la Apoptosis/metabolismo , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , Mutagénesis Sitio-Dirigida , Fenotipo , Regiones Promotoras Genéticas , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , ARN Interferente Pequeño/metabolismo , Survivin , Activación Transcripcional
15.
Cancer Sci ; 105(6): 630-8, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24703594

RESUMEN

Calpain small subunit 1 (Capn4) plays a key role in tumor migration or invasion. In this study, expression and function of Capn4 was investigated in human nasopharyngeal carcinoma (NPC). Here we report that both mRNA and protein levels of Capn4 were elevated in NPC tissues when compared to normal NP tissues. Similarly, Capn4 was also highly expressed in multiple NPC cell lines, compared to immortalized human nasopharyngeal epithelial cell line NP69. Moreover, expression of Capn4 was significantly correlated with Epstein-Barr virus infection, advanced stages, and lymph node or distant metastasis (P < 0.001). The patients with NPC displaying higher Capn4 had a significantly shorter overall survival (P = 0.002) and progression-free survival (P = 0.003). Furthermore, siRNA knockdown of Capn4 suppressed cell migration and invasion in vitro and in vivo. These events resulted from Capn4 downregulation were associated with reduced expression of matrix metalloproteinase 2 (MMP2), Snail, and Vimentin. Finally, we demonstrated that Capn4 upregulated MMP2 via nuclear factor-κB (NF-κB) activation, manifested by increased phosphorylation of p65, a subunit of NF-κB. Together, these findings argue a novel function of Capn4 in invasion and metastasis of NPC, and thereby suggest that Capn4 may represent an independent prognostic factor and a potential therapeutic target in NPC.


Asunto(s)
Biomarcadores de Tumor/biosíntesis , Calpaína/biosíntesis , Metaloproteinasa 2 de la Matriz/biosíntesis , Neoplasias Nasofaríngeas/patología , Factor de Transcripción ReIA/metabolismo , Animales , Biomarcadores de Tumor/genética , Cadherinas/biosíntesis , Calpaína/genética , Carcinoma , Línea Celular Tumoral , Movimiento Celular/genética , Supervivencia sin Enfermedad , Activación Enzimática , Infecciones por Virus de Epstein-Barr/metabolismo , Femenino , Adhesiones Focales/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/mortalidad , Invasividad Neoplásica , Metástasis de la Neoplasia , Fosforilación , Interferencia de ARN , ARN Mensajero/biosíntesis , ARN Interferente Pequeño , Factores de Transcripción de la Familia Snail , Factores de Transcripción/biosíntesis , Vimentina/biosíntesis
16.
Int J Clin Oncol ; 19(1): 106-12, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23299276

RESUMEN

BACKGROUND: Deleted in breast cancer 1 (DBC1) was initially cloned from a region homozygously deleted in breast cancers, but its role in colorectal cancer remains unknown. The present study aims to examine the expression level of DBC1 and assess its prognostic value in human colorectal cancer. METHODS: Immunohistochemical staining was performed to detect the expression level of DBC1 in a series of 186 colorectal cancer patients. Immunohistochemical staining results were analyzed and compared statistically with various clinicopathological characters and overall survival. RESULTS: Compared with the corresponding non-tumor tissues, a higher expression level of DBC1 was detected in colorectal cancer (P < 0.01). Tissue microarray analysis revealed that DBC1 expression is significantly associated with tumor histological grade, TNM stage and metastatic status (P < 0.01). Importantly, Kaplan-Meier analysis showed that DBC1 expression is associated with shorter overall survival (P < 0.01). Univariate Cox regression suggested that DBC1 expression, poorly differentiation status and the presence of lymph node metastasis predict shorter overall survival in colorectal cancer (P < 0.05). Multivariate Cox regression analysis indicated that DBC1 acts as an independent prognostic factor in colorectal cancer (P < 0.01). CONCLUSIONS: These results suggest that DBC1 is over-expressed in colorectal cancer and that it might serve as a predictor for selecting patients at high risk of poor prognosis.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/genética , Neoplasias Colorrectales/genética , Metástasis Linfática/genética , Anciano , Neoplasias Colorrectales/patología , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico
17.
Diagn Microbiol Infect Dis ; 75(3): 245-51, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23276768

RESUMEN

Clinical and experimental observations in animal models indicate that intestinal commensal bacteria are involved in the initiation and amplification of inflammatory bowel disease (IBD). As the majority of colonic bacteria cannot be identified by culture techniques, the aim of this study was to use sequence-based methods to investigate and characterize the composition of the dominant fecal microbiota in both patients with inflammatory bowel disease and healthy subjects. Fecal microbiota was isolated and quantified using real-time quantitative polymerase chain reaction. Denaturing gradient gel electrophoresis (DGGE) of 16S rDNA was used to evaluate the diversity of the dominant species. Analysis of individual bacterial groups showed a greater change in the fecal microbiota of patients with IBD, especially in those with active ulcerative colitis and active Crohn's disease. DGGE demonstrated the diversity of microbial flora in ulcerative colitis and Crohn's disease was less than in healthy subjects. Our results provide a better understanding of changes in fecal microbiota among patients with inflammatory bowel disease.


Asunto(s)
Colitis Ulcerosa/microbiología , Enfermedad de Crohn/microbiología , ADN Bacteriano/análisis , Heces/microbiología , Variación Genética , Metagenoma , Adulto , Anciano , Estudios de Casos y Controles , ADN Bacteriano/genética , Electroforesis en Gel de Gradiente Desnaturalizante , Femenino , Dosificación de Gen , Humanos , Masculino , Persona de Mediana Edad , ARN Ribosómico 16S/análisis , ARN Ribosómico 16S/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Adulto Joven
18.
Hepatology ; 57(2): 610-24, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22911555

RESUMEN

UNLABELLED: Recurrence and metastasis remain the most common causes of lethal outcomes in hepatocellular carcinoma (HCC) after curative resection. Thus, it is critical to discover the mechanisms underlying HCC metastasis. Forkhead box C1 (FoxC1), a member of the Fox family of transcription factors, induces epithelial-mesenchymal transition (EMT) and promotes epithelial cell migration. However, the role of FoxC1 in the progression of HCC remains unknown. Here, we report that FoxC1 plays a critical role in HCC metastasis. FoxC1 expression was markedly higher in HCC tissues than in adjacent noncancerous tissues. HCC patients with positive FoxC1 expression had shorter overall survival times and higher recurrence rates than those with negative FoxC1 expression. FoxC1 expression was an independent, significant risk factor for recurrence and survival after curative resection. FoxC1 overexpression induced changes characteristic of EMT and an increase in HCC cell invasion and lung metastasis. However, FoxC1 knockdown inhibited these processes. FoxC1 transactivated Snai1 expression by directly binding to the Snai1 promoter, thereby leading to the inhibition of E-cadherin transcription. Knockdown of Snai1 expression significantly attenuated FoxC1-enhanced invasion and lung metastasis. FoxC1 expression was positively correlated with Snai1 expression, but inversely correlated with E-cadherin expression in human HCC tissues. Additionally, a complementary DNA microarray, serial deletion, site-directed mutagenesis, and a chromatin immunoprecipitation assay confirmed that neural precursor cell expressed, developmentally down-regulated 9 (NEDD9), which promotes the metastasis of HCC cells, is a direct transcriptional target of FoxC1 and is involved in FoxC1-mediated HCC invasion and metastasis. CONCLUSIONS: FoxC1 may promote HCC metastasis through the induction of EMT and the up-regulation of NEDD9 expression. Thus, FoxC1 may be a candidate prognostic biomarker and a target for new therapies.


Asunto(s)
Carcinoma Hepatocelular/genética , Factores de Transcripción Forkhead/biosíntesis , Neoplasias Hepáticas/genética , Proteínas Adaptadoras Transductoras de Señales/biosíntesis , Adulto , Animales , Biomarcadores de Tumor/metabolismo , Cadherinas/biosíntesis , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Transición Epitelial-Mesenquimal , Femenino , Regulación Neoplásica de la Expresión Génica , Hepatitis B Crónica/fisiopatología , Humanos , Hígado/metabolismo , Neoplasias Hepáticas/patología , Neoplasias Pulmonares/secundario , Masculino , Ratones , Persona de Mediana Edad , Invasividad Neoplásica , Metástasis de la Neoplasia/genética , Metástasis de la Neoplasia/fisiopatología , Recurrencia Local de Neoplasia/fisiopatología , Fosfoproteínas/biosíntesis , Pronóstico , Factores de Transcripción de la Familia Snail , Factores de Transcripción/biosíntesis , Activación Transcripcional , beta Catenina/metabolismo
19.
FEBS J ; 279(19): 3652-3664, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22846196

RESUMEN

Gastric cancer is one of the leading causes of malignancy-related mortality in the world, and malignant growth is a crucial characteristic in gastric cancer. In our previous study, we found that growth arrest-specific gene 1 (GAS1) suppression was involved in making gastric cancer cells multidrug-resistant by protecting them from drug-induced apoptosis. In the present study, we investigated the potential role of GAS1 in the growth and proliferation of gastric cancer. We demonstrated that GAS1 expression was decreased in gastric cancer, and patients without GAS1 expression showed shorter survival times than those with GAS1 expression. Both gain-of-function (by overexpression of GAS1) and loss-of-function (by GAS1-specific small interfering RNA knockdown) studies showed that increased GAS1 expression significantly reduced the colony-forming ability of gastric cancer cells in vitro and reduced cell growth in vivo, whereas decreased GAS1 expression had the opposite effects. Moreover, upregulation of GAS1 induced cell apoptosis, and downregulation of GAS1 inhibited apoptosis. Furthermore, we demonstrated that GAS1 could induce gastric cancer cell apoptosis, at least in part through modulating the Bcl-2/Bax ratio and the activity of caspase-3. Taken together, our results strongly indicate that GAS1 expression was decreased in gastric cancer and was predictive of a poor prognosis. Restoration of GAS1 expression inhibited cell growth and promoted apoptosis of gastric cancer cells, at least in part through modulating the Bcl-2/Bax ratio and activating caspase-3, suggesting that GAS1 might be used as a novel therapeutic candidate for gastric cancer.


Asunto(s)
Proteínas de Ciclo Celular/metabolismo , Neoplasias Gástricas/metabolismo , Animales , Apoptosis , Western Blotting , Estudios de Casos y Controles , Caspasa 3/metabolismo , Ciclo Celular , Proteínas de Ciclo Celular/antagonistas & inhibidores , Proteínas de Ciclo Celular/genética , Línea Celular Tumoral , Proliferación Celular , Regulación hacia Abajo , Femenino , Estudios de Seguimiento , Proteínas Ligadas a GPI/antagonistas & inhibidores , Proteínas Ligadas a GPI/genética , Proteínas Ligadas a GPI/metabolismo , Mucosa Gástrica/metabolismo , Humanos , Técnicas para Inmunoenzimas , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , ARN Interferente Pequeño/genética , Estómago/patología , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Tasa de Supervivencia , Análisis de Matrices Tisulares , Proteína X Asociada a bcl-2/metabolismo
20.
Carcinogenesis ; 33(11): 2250-9, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-22831955

RESUMEN

The proliferation-specific transcription factor Forkhead box M1 (FoxM1) acts as a master regulator of cancer cell growth and survival and plays an important role in the development of hepatocellular carcinoma. However, the molecular mechanisms that regulate FoxM1 expression remain largely unknown. In the current study, we demonstrated that tumor necrosis factor (TNF)-αα induced FoxM1 expression and transactivated its promoter activity in hepatoma cells. Serial 5" deletion and site-directed mutagenesis revealed that the induction of FoxM1 expression by TNF-α was dependent upon the hypoxia-inducible factor 1 (HIF1)-1 and HIF1-3/4 binding sites within the FoxM1 promoter. Furthermore, at the transcriptional level, the stabilization of HIF-1α via reactive oxygen species generation led to the binding of HIF-1α to the FoxM1 promoter and resulted in increased FoxM1 expression. The inhibition of both HIF-1α expression and reactive oxygen species generation significantly decreased TNF-α-induced FoxM1 overexpression. Consequently, the upregulation of FoxM1 promoted the proliferation of hepatoma cells and enhanced their resistance to TNF-α-induced apoptosis. Consistently, there was a positive correlation between HIF-1α and FoxM1 expression in 406 human hepatocellular carcinoma tissues, and the combination of these two parameters was a powerful predictor of poor prognosis in hepatocellular carcinoma patients after curative resection. Here, we report a new molecular mechanism by which FoxM1 expression is regulated by the TNF-α/reactive oxygen species/HIF-1 pathway, and this mechanism results in the proliferation of hepatoma cells and their resistance to apoptosis.


Asunto(s)
Apoptosis , Carcinoma Hepatocelular/patología , Proliferación Celular , Factores de Transcripción Forkhead/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Factor de Necrosis Tumoral alfa/farmacología , Secuencia de Bases , Western Blotting , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidad , Hipoxia de la Célula , Línea Celular Tumoral , Inmunoprecipitación de Cromatina , Ensayo de Unidades Formadoras de Colonias , Estudios de Seguimiento , Proteína Forkhead Box M1 , Factores de Transcripción Forkhead/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Técnicas para Inmunoenzimas , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Datos de Secuencia Molecular , Recurrencia Local de Neoplasia/metabolismo , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Pronóstico , Regiones Promotoras Genéticas , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal , Tasa de Supervivencia , Activación Transcripcional , Regulación hacia Arriba
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