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1.
J Diabetes Res ; 2019: 5237371, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31281851

RESUMO

Background: To examine the association between morbid events and metabolic syndrome (MS) in patients with type 2 diabetes mellitus (T2DM). Methods: A prospective, longitudinal, multicenter study was conducted at 13 community health centers associated with Beijing Tongren Hospital. From 2008 to 2015, there have been 3,525 T2DM patients being managed based on the Chinese guideline for T2DM. The morbid events included macrovascular events, diabetic kidney disease, ophthalmologic events, cancer, and all-cause death. Results: At baseline, there were 2,708 people with MS and 817 without MS. After a seven-year management, there were 351 (12.96%) events in MS people and 74 (9.06%) events in people without MS (p = 0.003). The prevalence of macrovascular events (6.06%) was much higher in MS people than in people without MS (3.79%, p = 0.013). Cox regression analysis showed an association between MS and morbid events even after adjusting for confounding variables (adjusted hazard ratio = 1.44). MS was also associated with macrovascular events (adjusted hazard ratio = 1.96). The occurrence of morbid events and macrovascular events was increased when the numbers of metabolic abnormalities were 1, 2, 3, and 4 (p < 0.001). There was no continuously statistically significant difference in the cumulative prevalence of morbid events between patients with MS and patients without MS during the first five years. However, after six or seven years, the cumulative prevalence of morbid events in patients with MS was continuously significantly higher than that in patients without MS (11.00% vs. 8.20%, 12.96% vs. 9.06%, p < 0.05). Conclusions: T2DM with MS had higher incidence of morbid events, especially cardiovascular events, even after integrated management. The occurrence of morbid and macrovascular events increased as the number of metabolic abnormalities increased. MS was associated with increased risk of morbid events by 44% and macrovascular events by 96%. It would take at least six years to observe the association between MS and morbid events in T2DM.

5.
Diabetes Res Clin Pract ; 144: 236-244, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30218743

RESUMO

OBJECTIVE: We investigated the prognostic significance of metabolic risk scores and aspirin with respect to cerebrovascular events. METHODS: A total of 25 communities of diabetic patients were enrolled in Beijing Community Diabetes Study (BCDS) from 2008. 3413 patients with T2DM in BCDS have complete screening data, including blood glucose, blood pressure, lipid profiles and anti-platelet therapy, which were assigned metabolic score (MS) and add up to the total metabolic score (TMS). According to the total metabolic score (TMS), the patients were divided into four equal groups: Group 1 (24 < TMS < 40), Group 2 (40 < TMS < 47), Group 3 (47 < TMS < 55) and Group 4 (55 < TMS < 87). After 96 months, patients were followed-up to assess the long-term effects of the multifactorial interventions. RESULTS: During 96-months follow-up, a total of 91 cerebrovascular events occurred, including acute cerebral infarction, acute cerebral hemorrhage and transient ischemic attack (TIA). The incidence of cerebrovascular events was higher in the Group 4 than in the Group 1. In Cox multivariate analyses, there are significant differences in incidences of cerebral infarction events among the four groups during the 96-months follow-up. Cox proportional hazards analysis revealed that, HbA1c (p ≤ 0.001), systolic pressure (p ≤ 0.001), aspirin free treatment (P = 0.0023) are independent predictor for cerebrovascular events in diabetic patients. CONCLUSIONS: This study indicates that total metabolic score (TMS) influences the incidence of cerebrovascular events in diabetic patients. In addition to good control of blood glucose, blood pressure and lipid profiles, anti-platelet therapy is important for the prevention of cerebrovascular events in T2DM. TRIAL REGISTRATION: ChiCTR-TRC-13003978, ChiCTR-OOC-15006090.

7.
Ther Clin Risk Manag ; 14: 1537-1545, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30214217

RESUMO

Objective: It is well known that diabetic kidney disease is a risk factor for cardiovascular diseases (CVD) in patients with type 2 diabetes mellitus (T2DM). In this study, the effects of urine albumin excretion rate (AER) and estimated glomerular filtration rate (eGFR) on CVD outcomes were analyzed in a population of T2DM. Methods: The study was carried out using recorded information of a cohort study. A total of 1,914 patients with T2DM with no prevalent CVD were enrolled in an 8 years prospective study and received multifactorial intervention. The risk of CVD outcomes was assessed according to chronic kidney disease staging, which was categorized using AER (mg/d) and eGFR (mL/min/1.73 m2). The effects of AER and eGFR on risk of CVD onset were also analyzed. Results: During the follow-up period (median 6.8 years), 71 CVD events occurred. At baseline, those with AER ≥300 mg/d and coexisting eGFR 60-89 mL/min/1.73 m2 or <60 mL/min/1.73 m2 showed increased risk for CVD outcomes when compared with "no chronic kidney disease" (AER <30 mg/d and eGFR ≥90 mL/min/1.73 m2). The increased CVD risk was observed in patients who progressed to AER ≥30 mg/d during the follow-up period, whereas patients who progressed to eGFR <90 mL/min/1.73 m2 alone showed no increased CVD risk. During the follow-up period, after multifactorial intervention, 8.7% patients with microalbuminuria and 1.8% patients with overt nephropathy reversed to normoalbuminuria or microalbuminuria. Conclusion: AER is a more sensitive predictor than eGFR for CVD outcomes in T2DM patients. Overt nephropathy can be reversed after multifactorial intervention.

8.
Biomed Environ Sci ; 31(3): 242-246, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29673448

RESUMO

A case-control study was conducted to investigate associations between organophosphate pesticide (OP) exposure, aggression, impulsivity, and attempted suicide. Questionnaires were used to collect information; impulsivity and aggression were measured by the Barratt Impulsivity Scale (BIS) and the Aggression Inventory (AI). A greater number of OP symptoms was associated with an increased odds of a suicide attempt after adjusting for marital status and income (OR = 1.45; CI 1.14-1.86). Attempted suicide was significantly associated with high impulsivity scores (means: 72.4 vs. 60.6, P < 0.0001) and high aggression scores (means: 38.5 vs. 26.1, P < 0.0001). Suicide attempters had a higher number of OP exposure symptoms than controls and scored higher on scales of impulsivity and aggression.


Assuntos
Agressão , Comportamento Impulsivo , Exposição Ocupacional , Intoxicação por Organofosfatos/complicações , Praguicidas/efeitos adversos , Tentativa de Suicídio/estatística & dados numéricos , Adulto , Estudos de Casos e Controles , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Organofosfatos/efeitos adversos , Fatores de Risco
9.
Clin Nurs Res ; : 1054773818773385, 2018 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-29695172

RESUMO

The purpose of this study was to explore the relationship between the metabolic syndrome severity Z-score and kidney function by gender. We also examined the estimated glomerular filtration rate in relation to other known risk factors. The study used was a population-based prospective longitudinal research design. A total of 4,838 participants (2,683 females and 2,155 males) included individuals aged >30 years who were undergoing a health examination from 2006 to 2014 in Pingzhen City, Taiwan. In the initial generalized estimated equation model analysis, which included the covariates of age of first visit, period between the first and current visit, and metabolic syndrome severity Z-score, the results indicated that the interaction between age and metabolic syndrome severity Z-score is significantly related to the estimated glomerular filtration rate for males ( p = .040). For females, the interaction between age and metabolic syndrome severity Z-score was not significant, but a higher metabolic syndrome severity Z-score was significantly associated with lower estimated glomerular filtration rate ( p = .001). After controlling for the confounders, unhealthy behaviors, and comorbidities, the metabolic syndrome severity Z-score was still a negative predictor of estimated glomerular filtration rate in both the male ( p = .005) and female ( p = .023) models.

10.
Zhongguo Dang Dai Er Ke Za Zhi ; 20(2): 140-145, 2018 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-29429464

RESUMO

OBJECTIVE: To investigate the association between dopamine D4 receptor gene DRD4 exon III 48bp variable number of tandem repeat (VNTR) polymorphism and temperament in school-aged children. METHODS: Randomized cluster sampling was used to select 350 healthy children aged 8-12 years, and a questionnaire survey was performed. Oral epithelial samples were collected from half of these children. The complete questionnaire data of 164 children with a high level of DNA in oral epithelial samples were included in this study. PCR was used for the typing of DRD4 exon III 48bp VNTR, and the effect of this gene and its interaction with the environment on temperament was analyzed. RESULTS: Compared with the children with S-DRD4 genotype, the children with L-DRD4 genotype had significantly lower scores on the four dimensions of activity level, reaction intensity, emotion essence, and persistence (P<0.05). The main effects of mother's rejection/denial (OR=2.281, P<0.05) and sex (OR=2.766, P<0.05) and the interaction between sex and DRD4 exon III 48bp VNTR (OR=0.582, P<0.05) had an influence on activity level. The main effect of DRD4 exon III 48bp VNTR (OR=0.314, P<0.01) and the interaction between this gene and mother's rejection/denial (OR=1.872, P<0.01) had an influence on reaction intensity. The main effect of DRD4 exon III 48bp VNTR (OR=0.420, P<0.05) and mother's rejection/denial (OR=2.236, P<0.05) had an influence on persistence. CONCLUSIONS: DRD4 exon III 48bp VNTR and its interaction with other factors may affect the activity level and reaction intensity of school-aged children.


Assuntos
Éxons , Repetições Minissatélites , Receptores de Dopamina D4/genética , Temperamento , Criança , Feminino , Humanos , Masculino
11.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 25(6): 1744-1750, 2017 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-29262909

RESUMO

OBJECTIVE: To investigate the feasibility and relibility of rapidly and accurately acquiring the informations of gene mutations in MPN patients by using self-designed custom MPN mutation-related multipe-PCR primer kit and next generation Ion Torrent PGM sequencing platform. METHODS: The bone marrow samples of 10 MPN patients with JAK2V617F and/or CALR+, Ph- confirmed by sanger sequencing method were collected and were re-detected by using next generation Ion Torrent PGM sequencing method, then the consistence of results of above-mentioned 2 kinds of detection methods was compared. RESULTS: In terms of JAK2V617F, MPL and CALR mutations, the results of Ion Torrent PGM sequencing were complete consistent with results of Sanger sequencing, except 52 bp deletion of CALR gene, which conld not be detected by next generation Ion Torrent PGM sequencing method in all bone marrow samples. CONCLUSION: The detection of multiple gene mutations in MPN patients by Ion Torrent PGM sequencing platform is feasible and can meet the needs of clinical testing. This method can complete detection of all 23 mutetions within 1-2 days, moreover, possesses advantages of high sensitivity, specificity, rapidity, high throughput and low cost.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Mutação , Transtornos Mieloproliferativos/genética , Humanos , Deleção de Sequência
12.
Int J Nanomedicine ; 12: 1065-1083, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28223799

RESUMO

Here, we report the hypoxia-responsive ionizable liposomes to deliver small interference RNA (siRNA) anticancer drugs, which can selectively enhance cellular uptake of the siRNA under hypoxic and low-pH conditions to cure glioma. For this purpose, malate dehydrogenase lipid molecules were synthesized, which contain nitroimidazole groups that impart hypoxia sensitivity and specificity as hydrophobic tails, and tertiary amines as hydrophilic head groups. These malate dehydrogenase molecules, together with DSPE-PEG2000 and cholesterol, were self-assembled into O'1,O1-(3-(dimethylamino)propane-1,2-diyl) 16-bis(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl) di(hexadecanedioate) liposomes (MLP) to encapsulate siRNA through electrostatic interaction. Our study showed that the MLP could deliver polo-like kinase 1 siRNA (siPLK1) into glioma cells and effectively enhance the cellular uptake of MLP/siPLK1 because of increased positive charges induced by hypoxia and low pH. Moreover, MLP/siPLK1 was shown to be very effective in inhibiting the growth of glioma cells both in vitro and in vivo. Therefore, the MLP is a promising siRNA delivery system for tumor therapy.


Assuntos
Sistemas de Liberação de Medicamentos , Glioma/terapia , Lipossomos/química , RNA Interferente Pequeno/metabolismo , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Proteínas de Ciclo Celular/metabolismo , Hipóxia Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Endocitose/efeitos dos fármacos , Glioma/patologia , Humanos , Malato Desidrogenase/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Fosfatidiletanolaminas/química , Polietilenoglicóis/química , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Ratos , Análise Espectral
13.
Ying Yong Sheng Tai Xue Bao ; 28(2): 554-562, 2017 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-29749164

RESUMO

In order to analyze the effects of combined application of water retention agent and orga-nic fertilizer on physico-chemical properties of iron tailings and to find the optimal proportion of water retention agent and organic fertilizer for the improvement of iron tailings, the experimental plots of the combination trials with 2 factors in 4 levels were designed in the iron tailings of Qian'an Shougang through investigating some indexes of physico-chemical properties such as bulk density, moisture capacity, porosity, pH and the contents of organic matter, nitrogen, phosphorus and potas-sium. The biomasses of Medicago sativa and Amorpha fruticosa planted in the experimental plots were measured to verify the improvement effects. 4 levels of super absorbent polymers (L·m-3) used in treatments were 0 (B0), 10 (B1), 50 (B2), 100 (B3), and 4 levels of organic fertilizer (kg·m-2) were 0(N0), 2.25 (N1), 11.24 (N2), 22.49 (N3). The improving effects of different treatments on physico-chemical properties of iron tailings were mainly reflected in the surface layer of 0-20 cm. All the tested indexes were significantly different from control (CK) in the layer of 0-20 cm. The improvement effects of organic fertilizer on physical and chemical properties of iron tai-lings were better than that of water retention agent. In the 0-20 cm layer, the bulk density, non-capillary porosity, organic matter, rapidly available phosphorus, and available potassium under all treatments of adding water retention agent individually were not significantly different from the CK, while significant difference was observed when the organic fertilizer was solely applied in B0N2 and B0N3 treatments. The improvement synergy effect of organic fertilizer and water retention agent was better than that of organic fertilizer or water retention agent, respectively. In 0-20 cm layer, all the indexes obtained from treatment B3N3 performed best and were significantly different from the CK, which was the optimum for the improvement of iron tailings.


Assuntos
Fertilizantes , Ferro , Solo , Nitrogênio , Fósforo
14.
Inorg Chem ; 55(22): 11821-11830, 2016 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-27934302

RESUMO

Metal-organic frameworks (MOFs) have attracted great attention in the past years due to their diverse structures as well as interesting properties. However, MOFs with multifunctionality are still challenging. Under solvothermal conditions, reactions of 1,3,5-tris(1-imidazolyl)benzene (tib) and 4,4',4″-benzene-1,3,5-triyl-tribenzoic acid (H3BTB) with Cd(II) salt give rise to two novel MOFs [Cd3(tib)2(BTB)2]·3DEF·4.5H2O (1) and [Cd3(tib)2(BTB)2(DMA)2(H2O)2]·2DMA·8H2O (2) (DEF = N,N-diethylformamide, DMA = N,N-dimethylacetamide) with three-dimensional framework structures. It is fascinating that 1 and 2 not only show unique selectivity for detection of acetone through fluorescence quenching mechanism but also exhibit selective adsorption of gas (CO2 over N2 at 298 K) and dye (methyl orange) molecules.

15.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 24(6): 1665-1669, 2016 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-28024474

RESUMO

OBJECTIVE: To explore the role of heterogeneous nuclear ribonucleoprotein(hnRNP) K regulating autophagy in the drug resistance of acute myeloid leukemia, so as to provide a new molecular marker for treatment of leukemia. METHODS: The relationship between the expression level of hnRNP K and the drug resistance of myeloid leukemia was verified by fluorescence quantitative PCR; the expression of autophagy related protein LC3I/ II was detected by Western blot after the hnRNP K was modulated by RNA interference technology; the sensitivity of leukemia cells to doxorubicin was analyzed before and after the expression of hnRNP K were modulatd. RESULTS: The expression of hnRNP K and LC3I/II significantly increased in bone marrow nonremission patients and in drug resistant cell line, however, the expression of LC3I/ II decreased when the expression of hnRNP K were reduced, while the sensitivity of cells to adriamycin could be recovered. CONCLUSION: hnRNP K may be involved in the formation of adriamycin resistance in acute myeloid leukemia by regulating autophagy.


Assuntos
Leucemia Mieloide Aguda , Autofagia , Linhagem Celular Tumoral , Doxorrubicina , Resistencia a Medicamentos Antineoplásicos , Ribonucleoproteínas Nucleares Heterogêneas Grupo K , Humanos , Interferência de RNA
16.
Artigo em Inglês | MEDLINE | ID: mdl-27669272

RESUMO

Recent studies in PM2.5 sources show that anthropogenic emissions are the main contributors to haze pollution. Due to their essential roles in establishing policies for improving air quality, socioeconomic drivers of PM2.5 levels have attracted increasing attention. Unlike previous studies focusing on the annual PM2.5 concentration (Cyear), this paper focuses on the accumulation phase of PM2.5 during the pollution episode (PMAE) in the Yangtze River Delta in China. This paper mainly explores the spatial variations of PMAE and its links to the socioeconomic factors using a geographical detector and simple linear regression. The results indicated that PM2.5 was more likely to accumulate in more developed cities, such as Nanjing and Shanghai. Compared with Cyear, PMAE was more sensitive to socioeconomic impacts. Among the twelve indicators chosen for this study, population density was an especially critical factor that could affect the accumulation of PM2.5 dramatically and accounted for the regional difference. A 1% increase in population density could cause a 0.167% rise in the maximal increment and a 0.214% rise in the daily increase rate of PM2.5. Additionally, industry, energy consumption, and vehicles were also significantly associated with PM2.5 accumulation. These conclusions could serve to remediate the severe PM2.5 pollution in China.


Assuntos
Poluentes Atmosféricos/provisão & distribução , Poluição do Ar/estatística & dados numéricos , Monitoramento Ambiental , Resíduos Industriais/estatística & dados numéricos , Material Particulado/provisão & distribução , Rios/química , Emissões de Veículos/análise , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , China , Cidades , Humanos , Resíduos Industriais/efeitos adversos , Resíduos Industriais/análise , Centrais Elétricas , Smog/efeitos adversos , Smog/análise , Urbanização , Compostos Orgânicos Voláteis/efeitos adversos , Compostos Orgânicos Voláteis/provisão & distribução
17.
Sci Rep ; 6: 33437, 2016 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-27625176

RESUMO

Chinese Cordyceps, known in Chinese as "DongChong XiaCao", is a parasitic complex of a fungus (Ophiocordyceps sinensis) and a caterpillar. The current study explored the endogenetic fungal communities inhabiting Chinese Cordyceps. Samples were collected from five different geographical regions of Qinghai and Tibet, and the nuclear ribosomal internal transcribed spacer-1 sequences from each sample were obtained using Illumina high-throughput sequencing. The results showed that Ascomycota was the dominant fungal phylum in Chinese Cordyceps and its soil microhabitat from different sampling regions. Among the Ascomycota, 65 genera were identified, and the abundant operational taxonomic units showed the strongest sequence similarity to Ophiocordyceps, Verticillium, Pseudallescheria, Candida and Ilyonectria Not surprisingly, the genus Ophiocordyceps was the largest among the fungal communities identified in the fruiting bodies and external mycelial cortices of Chinese Cordyceps. In addition, fungal communities in the soil microhabitats were clustered separately from the external mycelial cortices and fruiting bodies of Chinese Cordyceps from different sampling regions. There was no significant structural difference in the fungal communities between the fruiting bodies and external mycelial cortices of Chinese Cordyceps. This study revealed an unexpectedly high diversity of fungal communities inhabiting the Chinese Cordyceps and its microhabitats.


Assuntos
Cordyceps/genética , Variação Genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Hypocreales/genética , Sequência de Bases , Análise por Conglomerados , Cordyceps/ultraestrutura , DNA Espaçador Ribossômico/genética , Ecossistema , Carpóforos/ultraestrutura , Micélio/ultraestrutura , Análise de Componente Principal
18.
Cancer Biol Med ; 13(2): 206-14, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27458528

RESUMO

Vascular endothelial growth factor (VEGF) is primarily known as a proangiogenic factor and is one of the most important growth and survival factors affecting the vascular endothelium. However, recent studies have shown that VEGF also plays a vital role in the immune environment. In addition to the traditional growth factor role of VEGF and VEGF receptors (VEGFRs), they have a complicated relationship with various immune cells. VEGF also reportedly inhibits the differentiation and function of immune cells during hematopoiesis. Dendritic cells (DCs), macrophages, and lymphocytes further express certain types of VEGF receptors. VEGF can be secreted as well by tumor cells through the autocrine pathway and can stimulate the function of cancer stemness. This review will provide a paradigm shift in our understanding of the role of VEGF/VEGFR signaling in the immune and cancer environment.

19.
Zhongguo Dang Dai Er Ke Za Zhi ; 18(6): 501-5, 2016 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-27324537

RESUMO

OBJECTIVE: To study the effects of rs4274224 polymorphisms in the DRD2 gene, family factors and their interaction on the regularity in school-age children. METHODS: The rs4274224 polymorphisms were genotyped using Sequenom Mass Array. The regularity was assessed based on the Middle Childhood Temperament Questionnaire (MCTQ). The parental rearing pattern was assessed with Egna Minnen av Bardnodnauppforstran (EMBU). The family function was assessed using Family Cohesion and Adaptability Scale (FACES II-CV). RESULTS: The regularity score in children with AA genotype of rs4274224 in the DRD2 gene was significantly lower than in those with GA/GG genotype (2.9±0.6 vs 3.1±0.7; P<0.05). The results of multiple regression analysis showed that the regularity was related to child gender, father's education level and family adaptability. The results of logistic regression analysis showed that the main factors influencing the regularity were family adaptability and its interaction with rs4274224 polymorphisms. The regularity was better in children with high family adaptability than in those with low family adaptability (OR=0.112, P<0.01). The children with AA genotype and low family adaptability were tend to be associated with low regularity (OR=21.554, P<0.01). CONCLUSIONS: The regularity based the temperament for school-age children might be influenced by family adaptability and its interaction with rs4274224 polymorphisms.


Assuntos
Polimorfismo Genético , Receptores de Dopamina D2/genética , Temperamento , Criança , Feminino , Genótipo , Humanos , Masculino , Inquéritos e Questionários
20.
Int J Med Sci ; 13(5): 365-73, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27226777

RESUMO

INTRODUCTION: The mechanism of EphB4/ephrinB2 in the resistance of chronic myelogenous leukemia to imatinib keeps unknown. METHODS: The imatinib resistant chronic myelogenous leukemia cell line-K562-R, was established. EphB4 receptor expression was detected in patients and resistant cells. Cell migration and drug sensitivity were tested in the EphB4 knockdown cells and mouse models. RESULTS: The EphB4 receptor was over-expressed in blast crisis patients compared to chronic phase patients. The level of EphB4 receptor expression was associated with a complete cytogenetic response within 12 months. Enhanced expression of the EphB4 receptor was detected in the K562-R cells. EphB4 knockdown inhibited cell migration ability and restored sensitivity to imatinib in vitro and in vivo. Restored sensitivity to imatinib was observed in K562-R cells, along with increased levels of phospho-EphB4 and decreased phosphorylation levels of RhoA, Rac1, and Cdc42. CONCLUSION: Our study illustrates that aberrant activation of EphB4/ephrinB2 may mediate chronic myeloid leukemia resistance involved in cytoskeletal proteins.


Assuntos
Antineoplásicos/uso terapêutico , Proteínas do Citoesqueleto/metabolismo , Efrina-B2/metabolismo , Mesilato de Imatinib/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Receptor EphB4/metabolismo , Animais , Movimento Celular/genética , Movimento Celular/fisiologia , Proteínas do Citoesqueleto/genética , Resistencia a Medicamentos Antineoplásicos/genética , Efrina-B2/genética , Feminino , Humanos , Células K562 , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Camundongos , Camundongos Nus , Fosforilação/genética , Fosforilação/fisiologia , Receptor EphB4/genética , Ensaios Antitumorais Modelo de Xenoenxerto , Proteína cdc42 de Ligação ao GTP/metabolismo , Proteínas rac1 de Ligação ao GTP/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismo
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