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1.
RSC Adv ; 14(21): 15155-15166, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38725563

RESUMEN

Monolithic adsorbent removal of fluoride from water is considered an effective and non-secondary pollution method. Here, a portable hydroxyl-functionalized coal gangue-based cordierite porous ceramic sheet (ACGC-Fe) is prepared by using coal gangue solid waste with a specific silicon-aluminum-rich composition ratio and a small amount of magnesium oxide as a raw material through powder compression molding and mild chemical modification. The prepared ACGC-Fe can be used to treat fluorine-containing wastewater and the maximum adsorption of fluorine can reach 18.69 mg g-1. The Langmuir (Freundlich) adsorption isotherm model and pseudo-second-order kinetic model here provided a satisfactory description of the fluoride removal operating mechanism, and it is confirmed that the adsorption mechanism of ACGC-Fe is mainly attributed to the chemisorption of hydrogen bonds (with hydroxyl group) and ionic bonds (with metal), and physical adsorption based on cordierite porous ceramic pores. This research will provide a new idea for designing high-performance materials by mining and analyzing the composition and structure characteristics of coal gangue solid waste itself and broaden the application range of high-value-added coal gangue solid waste.

2.
Adv Sci (Weinh) ; 10(26): e2302361, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37431193

RESUMEN

Lightweight and flexible electronic materials with high energy attenuation hold an unassailable position in electromagnetic stealth and intelligent devices. Among them, emerging heterodimensional structure draws intensive attention in the frontiers of materials, chemistry, and electronics, owing to the unique electronic, magnetic, thermal, and optical properties. Herein, an intrinsic heterodimensional structure consisting of alternating assembly of 0D magnetic clusters and 2D conductive layers is developed, and its macroscopic electromagnetic properties are flexibly designed by customizing the number of oxidative molecular layer deposition (oMLD) cycles. This unique heterodimensional structure features highly ordered spatial distribution, with an achievement of electron-dipole and magnetic-dielectric double synergies, which exhibits the high attenuation of electromagnetic energy (160) and substantial improvement of dielectric loss tangent (≈200%). It can respond to electromagnetic waves of different bands to achieve multispectral stealth, covering visible light, infrared radiation, and gigahertz wave. Importantly, two kinds of ingenious information interaction devices are constructed with heterodimensional structure. The hierarchical antennas allow precise targeting of operating bands (S- to Ku- bands) by oMLD cycles. The strain imaging device with high sensitivity opens a new horizon for visual interaction. This work provides a creative insight for developing advanced micro-nano materials and intelligent devices.

3.
J Pharm Biomed Anal ; 233: 115496, 2023 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-37285658

RESUMEN

A study on the polysorbate 80 stability in various formulation buffers commonly used in biopharmaceuticals was performed, to investigate the excipients influence on polysorbate 80 degradation. Polysorbate 80 is a common excipient in biopharmaceutical products. However, its degradation will potentially impact the drug product quality, and may trigger protein aggregation and particles formation. Due to the heterogeneity of the polysorbates and the mutual effects with other formulation compositions, the study of polysorbate degradation is challenging. Herein, a real-time stability study was designed and performed. The polysorbate 80 degradation trend was monitored by fluorescence micelle-based assay (FMA), reversed-phase-ultra-performance liquid chromatography-evaporative light scattering detector (RP-UPLC-ELSD) assay, and LC-MS assay. These assays provide orthogonal results to reveal both the micelle-forming capability and the compositional changes of polysorbate 80 in different buffer systems. The degradation occurred after a period of storage under 25 °C in different trend, which indicates the excipients could impact the degradation kinetics. Upon comparison, the degradation is prone to happen in histidine buffer than in acetate, phosphate or citrate buffers. LC-MS confirms oxidation as an independent degradation pathway with detection of the oxidative aldehyde. Thus, it is necessary to pay more attention to the excipients selection and their potential impact on polysorbate 80 stability to achieve longer shelf life for the biopharmaceuticals. Besides, the protective roles of several additives were figured out, which could be applied as potential industrial solutions to the polysorbate 80 degradation issues.


Asunto(s)
Productos Biológicos , Polisorbatos , Excipientes , Micelas , Cromatografía Líquida de Alta Presión/métodos , Tampones (Química)
4.
Nanomicro Lett ; 15(1): 142, 2023 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-37258997

RESUMEN

Advanced electromagnetic devices, as the pillars of the intelligent age, are setting off a grand transformation, redefining the structure of society to present pluralism and diversity. However, the bombardment of electromagnetic radiation on society is also increasingly serious along with the growing popularity of "Big Data". Herein, drawing wisdom and inspiration from nature, an eco-mimetic nanoarchitecture is constructed for the first time, highly integrating the advantages of multiple components and structures to exhibit excellent electromagnetic response. Its electromagnetic properties and internal energy conversion can be flexibly regulated by tailoring microstructure with oxidative molecular layer deposition (oMLD), providing a new cognition to frequency-selective microwave absorption. The optimal reflection loss reaches ≈ - 58 dB, and the absorption frequency can be shifted from high frequency to low frequency by increasing the number of oMLD cycles. Meanwhile, a novel electromagnetic absorption surface is designed to enable ultra-wideband absorption, covering almost the entire K and Ka bands. More importantly, an ingenious self-powered device is constructed using the eco-mimetic nanoarchitecture, which can convert electromagnetic radiation into electric energy for recycling. This work offers a new insight into electromagnetic protection and waste energy recycling, presenting a broad application prospect in radar stealth, information communication, aerospace engineering, etc.

5.
BMC Pediatr ; 21(1): 65, 2021 02 05.
Artículo en Inglés | MEDLINE | ID: mdl-33546645

RESUMEN

BACKGROUND: The incidence of pertussis shows an increasing trend in recent years, but some clinicians often lack sufficient understanding of the clinical characteristics and risk factors for severe pertussis, and more effective measures should be taken to reduce the incidence and mortality of pertussis in young infants METHODS: A retrospective study was conducted, and 184 infants and children with pertussis who had been hospitalized in the Department of Pediatrics of Beijing Ditan Hospital affiliated with Capital Medical University from January 2016 to December 2017 were included. Clinical data of the patients were collected and the clinical characteristics were statistically analyzed RESULTS: Among the 184 patients, 41.85% were infants < 3 months of age, and 65.22% of the total patients were not vaccinated against pertussis. There were 22 critically ill children, among whom 4 died, and compared with mild cases, they had a higher proportion of children younger than 3 months of age and infants not vaccinated against pertussis (63.64% vs. 38.89% and 100% vs. 60.49%, respectively); a higher proportion of children with severe pneumonia (100% vs. 0%); higher leukocyte count(× 109/L , 35.80 ± 20.53 vs 19.41 ± 8.59); and a higher proportion of children with severe hyperleukocytosis (18.18% vs. 0%, respectively) (P<0.05) CONCLUSIONS: 1. Infants aged <3 months not vaccinated for pertussis appear more likely to become infected and have more severe disease. 2. Severe pneumonia and hyperleukocytosis are the main mechanisms underlying severe pertussis.


Asunto(s)
Neumonía , Tos Ferina , Anciano , Niño , Humanos , Incidencia , Lactante , Estudios Retrospectivos , Factores de Riesgo , Tos Ferina/diagnóstico , Tos Ferina/epidemiología , Tos Ferina/prevención & control
6.
Pediatr Investig ; 4(4): 230-235, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33376949

RESUMEN

IMPORTANCE: Within the coronavirus disease 2019 (COVID-19) global pandemic, more attention is warranted for whether this new infectious disease has unique manifestations in children. OBJECTIVE: To retrospectively determine the epidemiological and clinical characteristics of 35 children with COVID-19 in Beijing, China. METHODS: We collected data for 35 children diagnosed with COVID-19 who were admitted to Beijing Ditan Hospital from January 2020 to June 2020, and analyzed their epidemiological characteristics, clinical manifestations, laboratory examinations, chest imaging findings, treatments, and outcomes. RESULTS: The children comprised 18 boys (51.4%) and 17 girls (48.6%) aged 6 months to 15 years. All patients had clear epidemiological history, with family clusters accounting for 28 cases (80.0%) and clear tracing of exposure to high epidemic areas in the remaining 7 cases (20.0%). Four (11.4%) patients were classified as asymptomatic, 17 (48.6%) as acute upper respiratory infection, and 14 (40.0%) as mild pneumonia, with no severe or critical cases. Clinical manifestations were mild, including fever in 18 (51.4%), cough in 14 (40.0%), and nausea and diarrhea in 7 (20.0%) patients. White blood cell count was mostly normal (26 cases, 74.3%) or decreased (7 cases, 20.0%); lymphocyte percentage was increased in 24 (68.7%); neutrophil percentage was decreased in 25 (71.4%); alanine aminotransferase was increased in 3 (8.6%); and serum potassium was decreased in 4 (11.4%). Time to negative viral nucleic acid testing was 2-42 days (mean: 14.0 ± 9.4 days). Chest imaging examination revealed that 20 patients (57.1%) had different forms of lung inflammation. Treatment was mainly isolation and nutritional support. Eleven patients were treated with interferon atomization inhalation. No patients required oxygen therapy. All 35 children were cured and discharged. Length of hospital stay was 9-54 days (mean: 25.4 ± 13.8 days). During regular follow-up after discharge, 5 children showed positivity again in the viral nucleic acid test and were re-hospitalized for observation and treatment. The mean length of re-hospitalization stay was 10.8 days. INTERPRETATION: Children with COVID-19 mainly become infected within their family, and children of all ages are generally susceptible. The disease in children is mostly mild and the prognosis is good. Nucleic acid tests in some patients become positive again after discharge, suggesting that it is of great significance to carry out centralized isolation medical observations and active nucleic acid tests in close contacts for early detection of patients and routine epidemic prevention and control.

7.
Zhonghua Yi Xue Za Zhi ; 94(12): 938-43, 2014 Apr 01.
Artículo en Chino | MEDLINE | ID: mdl-24854917

RESUMEN

OBJECTIVE: To explore the changes of expression and biological activity of nuclear factor-kappa B (NF-κB) and matrix metalloproteinase-9 (MMP-9) after using intravenous immunoglobulin (IVIG) in a murine model of Kawasaki disease (KD) and elucidate the therapeutic mechanism of IVIG for the treatment of KD. METHODS: A total of 72 mice were categorized randomly into IVIG, KD and control groups.Lactobacillus casei cell wall extract (LCWE) was prepared and injected intraperitoneally into C57BL/6 mice to induce KD (0.5 mg single injection).IVIG group received an intraperitoneal injection of IVIG (2 mg/g) while KD model group had an intraperitoneal injection of normal saline. At Days 14, 28 and 56, the diameter of coronary artery was by echocardiography in 8 mice of each group. At the same time, the stains of hematoxylin & eosin and elastic fiber were used to observe the pathological damage of coronary artery. Western blot was used to evaluate the expressions of NF-κB and MMP-9, electrophoretic mobility shift assay (EMSA) was used to measure the activity of NF-κB and Gelatin zymography was used to evaluate the activity of MMP-9 in heart samples of murine model of KD. RESULTS: The local inflammatory infiltrate, composed predominantly of mononuclear lymphocytes, of coronary artery trunk and branches was observed at Days 14 and 28 while broken elastin was observed at Day 56. And the inflammatory cell infiltrate was less severe and no apparent broken elastin was observed in IVIG and control groups. On echocardiography, the average value of diameter of left coronary artery in KD model group was higher than that in IVIG and control groups (28 d:(0.48 ± 0.07) vs (0.41 ± 0.03) and (0.35 ± 0.02) mm, all P < 0.01). Compared with the other two groups, the result of Western blot showed that the expressions of NF-κB and MMP-9 in KD model group were markedly higher than those in IVIG treatment group and that in control group at each time point (28 d: (58 ± 14) vs (25 ± 14) & (19 ± 11) µg/L, (100 ± 41) vs (39 ± 19) & (35 ± 19) µg/L, all P < 0.01). The activity of NF-κB by EMSA and the result from KD model group were much higher than those from the control and IVIG groups (28 d: (84 788 ± 2 081) vs (27 220 ± 4 990) & (50 192 ± 1 586) µg/L, all P < 0.01]. And it was in accord with the expression of NF-κB. The outcome of gelatin zymography demonstrated that the activity of MMP-9 had similar change with the expression of MMP-9(18 560 ± 7 963) vs (9 112 ± 3 398) & (11 834 ± 4 996) µg/L, all P < 0.05). CONCLUSIONS: NF-κB/MMP-9 is overexpressed and over-activated in the heart of KD mouse models. IVIG may inhibit the inflammatory cell infiltration and alleviate coronary artery. And such a therapeutic effect is possibly achieved by a suppression of the overexpression and over-activation of NF-κB/MMP-9 pathway.


Asunto(s)
Inmunoglobulinas Intravenosas/farmacología , Metaloproteinasa 9 de la Matriz/metabolismo , Síndrome Mucocutáneo Linfonodular/metabolismo , FN-kappa B/metabolismo , Animales , Modelos Animales de Enfermedad , Masculino , Ratones , Ratones Endogámicos C57BL , Síndrome Mucocutáneo Linfonodular/tratamiento farmacológico , Miocardio/metabolismo
8.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 20(6): 1346-51, 2012 Dec.
Artículo en Chino | MEDLINE | ID: mdl-23257430

RESUMEN

This study was aimed to explore the clinical significance of monitoring level of minimal residual disease (MRD) at different time point in B-lineage childhood acute lymphoblastic leukemia (B-ALL). Two hundred and six children with B-ALL were enrolled in this study from Augest 2008 to September 2011 in our hospital. MRD levels were detected by flow cytometry at day 15, 33 and week 12 after initial chemotherapy. The event-free survival (EFS) for patients based on MRD levels measured at different stages of chemotherapy were compared by Kaplan Meier analyses. The results showed that out of 206 cases 196 cases achieved complete remission (CR) after induction therapy (CR rate 95.1%), the 1- and 3-year EFS rate were (92.7 ± 1.8)% and (78.7 ± 3.7)%, respectively, and the 3-year EFS rate was (85.6 ± 4.9)% in standard risk group, (82.1 ± 5.8)% in intermediate risk group and (58.1 ± 9.2)% in high risk group, there was significant statistical difference between above mentioned 3 groups (P < 0.001). The MRD analysis at different time points showed that the higher the MRD level, the lower the 3-year EFS rate of children with ALL, in which the 3-year EFS rate of MRD ≥ 10(-2) at day 15, MRD ≥ 10(-3) at day 33 and MRD ≥ 10(-3) at week 12 were significantly lower. The MRD ≥ 10(-3) at week 12 was proven to be an independent predictor by multivariate Cox proportional-hazards regression model. The 3-year EFS rate for patients with MRD < 10(-3) and MRD ≥ 10(-3) at week 12 were (86.3 ± 4.1)% vs (55.8 ± 9.1)% (P < 0.05); 8 relapsed among 98 cases with negative MRD (MRD < 10(-4)) at day 33, 19 relapsed among 108 cases with positive MRD at day 33 between the two groups for recurrence rate has significant difference (P < 0.05). It is concluded that dynamically monitoring MRD by multi-parameter flow cytometry can precisely evaluate treatment response, judge treatment outcome and predict relapse in childhood B-ALL. The MRD 10(-2) at day 15, MRD 10(-3) at day 33 and MRD 10(-3) at week 12 should be considered as the best cut-off. MRD ≥ 10(-3) at week 12 was proven to be an independent factor of poor prognosis.


Asunto(s)
Citometría de Flujo/métodos , Neoplasia Residual/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Neoplasia Residual/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Pronóstico , Estudios Retrospectivos
9.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 20(3): 536-40, 2012 Jun.
Artículo en Chino | MEDLINE | ID: mdl-22739150

RESUMEN

This study was to explore the expression of two subtype molecules of CD133 and its relationship with clinical prognostic factors in childhood with B linage acute lymphoblastic leukemia (B-ALL) at initial diagnosis and the 33rd day of induction chemotherapy. Expression of CD133-1 and CD133-2 in 48 cases of B-ALL and 25 cases at initial diagnosis and the 33rd day of treatment was detected by flow cytometry. Minimal residual disease (MRD) of B-ALL at 33rd day was evaluated by flow cytometry. The results indicated that the expression of CD133-1 was positive in 18 cases (37.5%), and expression of CD133-2 in 30 cases (62.5%) was positive from 48 cases with newly diagnosed ALL (P < 0.05). At 33rd day of treatment, expression of CD133-1 in 2 cases (8.0%) from 25 cases was positive, and expression of CD133-2 in 23 cases (92.0%) was positive (P < 0.05). After induction chemotherapy in B-ALL, the expression of CD133-1 decreased significantly, but still higher than that in the normal control group. Compared to expression of CD133-1, expression of CD133-2 decreased slowly. It is concluded that there is no relations among expression of CD133 and sex, age, white blood cell count, percentage of bone marrow blast cells, FAB subtype, cytogenetics, leukemia fusion gene, risk stratification and complete remission rate in childhood B-ALL. The positive expression rates and levels of CD133-2 are higher than those of CD133-1 in B-ALL. There is no statistical correlation between expression of CD133 and CD34 in B-ALL. The expression of CD133-2 is significantly related to the level of MRD.


Asunto(s)
Antígenos CD/metabolismo , Glicoproteínas/metabolismo , Leucemia de Células B/metabolismo , Neoplasia Residual , Péptidos/metabolismo , Antígeno AC133 , Enfermedad Aguda , Adolescente , Antígenos CD/inmunología , Niño , Preescolar , Femenino , Regulación Leucémica de la Expresión Génica , Glicoproteínas/inmunología , Humanos , Lactante , Leucemia de Células B/inmunología , Masculino , Péptidos/inmunología
10.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 19(6): 1496-500, 2011 Dec.
Artículo en Chino | MEDLINE | ID: mdl-22169311

RESUMEN

This study was aimed to explore the clinical features and prognosis outcome of childhood T-cell acute lymphoblastic leukemia (T-ALL). The clinical data of 38 cases of newly diagnosed T-ALL from Jan 2005 to Aug 2010 were analyzed retrospectively, and 78 cases of B-ALL with intermediate and high risk were collected as control group, then the sensitive rate of patients to prednisone pretreatment, complete remission (CR) rate at day 33 after induction chemotherapy, relapse rate and 3-year event-free survival (EFS) were compared between T-ALL and B-ALL children. The results showed that no significant statistic difference were found in distribution of age, infiltration of liver, spleen and lymph nodes as well as central nervous system disease, chromosome abnormality, expression level of fusion gene and so on between T-ALL and B-ALL groups (p > 0.05), but there were significant differences in sex and number of cases with WBC count ≥ 50 × 10(9)/L between them (p < 0.05). The sensitive rate of T-ALL and B-ALL patients to prednisone pretreatment was 51.9% and 89.3% respectively (p < 0.05). The ratio failed to achieve CR at day 33 after induction chemotherapy was 15.4% and 8.1% in the two groups (p > 0.05). The relapse rate of T-ALL and B-ALL cases was 30.8% (8/26) and 14.9% (11/74) respectively (p > 0.05). The time from CR to relapse was (9.78 ± 3.48) month and (21.28 ± 14.32) month (p < 0.05). The 3 year EFS of T-ALL cases with intermediate and high risk was (37.5 ± 17.1)% and (22.2 ± 9.8)%, while 3 year EFS of B-ALL cases was (66.7 ± 7)% and (51.7 ± 9.3)% respectively (p < 0.05) according to Kaplan-Meier survival curve. It is concluded that as compared with B-ALL cases, the male ratio and initial WBC count are higher, moreover the early response to prednisone pretreatment and 3 year EFS are poor in T-ALL cases, the prognosis outcome is poor also.


Asunto(s)
Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Adolescente , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunofenotipificación , Lactante , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras B/mortalidad , Leucemia-Linfoma Linfoblástico de Células Precursoras/inmunología , Leucemia-Linfoma Linfoblástico de Células T Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/inmunología , Leucemia-Linfoma Linfoblástico de Células T Precursoras/mortalidad , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia
11.
J Transl Med ; 9: 211, 2011 Dec 08.
Artículo en Inglés | MEDLINE | ID: mdl-22152132

RESUMEN

BACKGROUND: Treatment failure for breast cancer is frequently due to lymph node metastasis and invasion to neighboring organs. The aim of the present study was to investigate invasion- and metastasis-related genes in breast cancer cells in vitro and in vivo. Identification of new targets will facilitate the developmental pace of new techniques in screening and early diagnosis. Improved abilities to predict progression and metastasis, therapeutic response and toxicity will help to increase survival of breast cancer patients. METHODS: Differential protein expression in two breast cancer cell lines, one with high and the other with low metastatic potential, was analyzed using two-dimensional liquid phase chromatographic fractionation (Proteome Lab PF 2D system) followed by matrix-assisted laser desorption/time-of-flight mass spectrometry (MALDI-TOF/MS). RESULTS: Up regulation of α-subunit of ATP synthase was identified in high metastatic cells compared with low metastatic cells. Immunohistochemical analysis of 168 human breast cancer specimens on tissue microarrays revealed a high frequency of ATP synthase α-subunit expression in breast cancer (94.6%) compared to normal (21.2%) and atypical hyperplasia (23%) breast tissues. Levels of ATP synthase expression levels strongly correlated with large tumor size, poor tumor differentiation and advanced tumor stages (P < 0.05). ATP synthase α-subunit over-expression was detected on the surface of a highly invasive breast cancer cell line. An antibody against the ATP synthase α-subunit inhibited proliferation, migration and invasion in these breast cancer cells but not that of a non-tumor derived breast cell line. CONCLUSIONS: Over-expression of ATP synthase α-subunit may be involved in the progression and metastasis of breast cancer, perhaps representing a potential biomarker for diagnosis, prognosis and a therapeutic target for breast cancer. This finding of this study will help us to better understand the molecular mechanism of tumor metastasis and to improve the screening, diagnosis, as well as prognosis and/or prediction of responses to therapy for breast cancer.


Asunto(s)
Neoplasias de la Mama/enzimología , Neoplasias de la Mama/terapia , ATPasas de Translocación de Protón Mitocondriales/antagonistas & inhibidores , Terapia Molecular Dirigida , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos/farmacología , Apoptosis/efectos de los fármacos , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Línea Celular Tumoral , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Cromatografía Liquida , Femenino , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Hiperplasia , Inmunohistoquímica , Persona de Mediana Edad , ATPasas de Translocación de Protón Mitocondriales/química , ATPasas de Translocación de Protón Mitocondriales/metabolismo , Invasividad Neoplásica , Subunidades de Proteína/antagonistas & inhibidores , Subunidades de Proteína/química , Subunidades de Proteína/metabolismo , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Análisis de Matrices Tisulares
12.
J Transl Med ; 9: 157, 2011 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-21936950

RESUMEN

BACKGROUND: Treatment failure for esophageal carcinoma is frequently due to lymph node metastasis and invasion to neighboring organs. The aim of the present study was to investigate invasion- and metastasis-related genes in esophageal carcinoma cells in vitro and in vivo. METHODS: A metastasis model using a Matrigel invasion clonal selection approach was employed to establish a highly invasive subline EC9706-P4 from the esophageal carcinoma cell (ESCC) line EC9706. The differentially expressed genes of the subline and the parental cells determined by gene microarrays were further analyzed by RT-PCR and Western blotting. RESULTS: We identified sphingosine kinase 1 (SPHK1) as an invasion and metastasis-related gene of esophageal cancer. SPHK1 was overexpressed in the EC9706-P4 subline with high invasive capacity. Among six ESCC lines tested, KYSE2 and KYSE30 cells showed the highest SPHK1 mRNA and protein expressions as well as the most invasive phenotype. By Western blotting, in 7/12 cases (58%), SPHK1 expression was higher in esophageal carcinomas than in the companion normal tissue. In 23/30 cases (76%), SPHK1 protein expression was upregulated in the tumors compared to matched normal tissue by immunohistochemistry (IHC). Esophageal carcinoma tissue microarray analysis indicated that SPHK1 expression correlated with the depth of tumor invasion (P < 0.0001) and lymph node metastasis (P = 0.016). By Kaplan-Meier analysis, strong SPHK1 expression was significantly associated with clinical failure (P < 0.01), suggesting the involvement of SPHK1 in aggressiveness of human esophageal carcinoma. SPHK1 overexpression significantly increased the invasiveness of EC9706 cells in vitro and also increased EC9706 cell growth and spontaneous metastasis in vivo, promoting significant increases in tumor growth, tumor burden and spontaneous lung metastasis in nude mice. SPHK1 expression significantly correlated with the expression of many EGFR pathway genes associated with invasion of cancer cells. SPHK1 protein expression also significantly correlated with the phosphorylation of EGFR. CONCLUSION: In summary, our data implicate SPHK1 in the metastasis of esophageal cancer. Our study also identified downstream mediators of SPHK1 in esophageal cancer cells that may mediate enhanced malignant behavior, and several of these mediators may be useful as therapeutic targets.


Asunto(s)
Neoplasias Esofágicas/enzimología , Neoplasias Esofágicas/patología , Metástasis Linfática/patología , Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismo , Animales , Línea Celular Tumoral , Activación Enzimática , Receptores ErbB/metabolismo , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/terapia , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Ratones , Invasividad Neoplásica , Transducción de Señal , Resultado del Tratamiento , Regulación hacia Arriba/genética
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