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1.
Zhonghua Nei Ke Za Zhi ; 62(9): 1114-1120, 2023 Sep 01.
Artículo en Chino | MEDLINE | ID: mdl-37650185

RESUMEN

Objective: To evaluate the effectiveness of enhanced CT texture feature analysis in predicting pseudoprogression in patients with metastatic clear cell renal cell carcinoma (mccRCC) undergoing programmed cell death protein 1 (PD-1) inhibitor therapy. Methods: A cross-sectional study. Data from 32 patients with mccRCC were retrospectively collected who received monotherapy with PD-1 inhibitors after standard treatment failure at Henan Cancer Hospital, from June 2015 to January 2021. Clinical information and enhanced CT images were analyzed to assess target lesion response. The lesions were divided into pseudoprogression and non-pseudoprogression groups. Manual segmentation of target lesions was performed using ITK-Snap software on baseline enhanced CT, and texture analysis was conducted using A.K. software to extract feature parameters. Differences in texture features between the pseudoprogression and non-pseudoprogression groups were analyzed using univariate and multivariate logistic regression. A predictive model for pseudoprogression was constructed, and its performance was evaluated using ROC curve analysis. Results: A total of 32 patients with 89 lesions were included in the study. Statistical analysis revealed significant differences in seven texture features between the pseudoprogression and non-pseudoprogression groups. These features included"original_ngtdm_Strength"(0.49 vs. -0.61,P=0.006), "wavelet-HLH_glszm_ZonePercentage"(0.67 vs. -0.22,P=0.024),"wavelet-LHL_ngtdm_Strength"(1.20 vs. -0.51,P=0.002), "wavelet-HLL_gldm_LargeDependenceEmphasis"(-0.84 vs. 0.19,P=0.002), "wavelet-HLH_glcm_Id" (-0.30 vs. 0.43,P=0.037),"wavelet- HLH_glrlm_RunPercentage"(0.45 vs. -0.01,P=0.032),"wavelet-LHH_firstorder_Skewness"(0.25 vs. -0.27, P=0.011). Based on these features, a pseudoprogression prediction model was developed with a P-value of 0.000 2 and an odds ratio of 0.045 (95%CI 0.009-0.227). The model exhibited a high predictive performance with an AUC of 0.907 (95%CI 0.817-0.997) according to ROC curve analysis. Conclusions: Enhanced CT texture feature analysis shows promise in predicting lesion pseudoprogression in patients with metastatic ccRCC undergoing PD-1 inhibitor therapy. The developed predictive model based on texture features demonstrates good performance and may assist in evaluating treatment response in these patients.


Asunto(s)
Carcinoma de Células Renales , Inhibidores de Puntos de Control Inmunológico , Humanos , Carcinoma de Células Renales/tratamiento farmacológico , Estudios Transversales , Estudios Retrospectivos , Tomografía Computarizada por Rayos X
2.
Zhonghua Er Ke Za Zhi ; 60(12): 1302-1306, 2022 Dec 02.
Artículo en Chino | MEDLINE | ID: mdl-36444434

RESUMEN

Objective: To explore the effect of vaccination on viral negative conversion of children with COVID-19. Methods: A retrospective cohort study was conducted. A cohort of 189 children aged 3-14 years with COVID-19 admitted to Renji Hospital (South branch) of Shanghai Jiao Tong University School of Medicine from April 7th to May 19th 2022 was enrolled in the study. According to the vaccination status, the infected children were divided into an unvaccinated group and a vaccinated group. Age, gender, severity, clinical manifestations, and laboratory tests, etc. were compared between groups, by rank sum test or chi-square test. The effects of vaccination on viral negative conversion were analyzed by a Cox mixed-effects regression model. Additionally, a questionnaire survey was conducted among the parents of unvaccinated children to analyze the reasons for not being vaccinated. Results: A total of 189 children aged 3-14 years were enrolled, including 95 males (50.3%) and 94 females (49.7%), aged 5.7 (4.1,8.6) years. There were 117 cases (61.9%) in the unvaccinated group and 72 cases (38.1%) in the vaccinated group. The age of the vaccinated group was higher than that of the unvaccinated group (8.8 (6.8, 10.6) vs. 4.5 (3.6, 5.9) years, Z=9.45, P<0.001). No significant differences were found in clinical manifestations, disease severity, and laboratory results between groups (all P>0.05), except for the occurrence rate of cough symptoms, which was significantly higher in the vaccinated group than in the non-vaccinated group (68.1% (49/72) vs. 50.4% (59/117),χ2=5.67, P=0.017). The Kaplan-Meier survival curve and Cox mixed-effects regression model showed that the time to the viral negative conversion was significantly shorter in the vaccinated group compared with the unvaccinated group (8 (7, 10) vs. 11 (9, 12) d, Z=5.20, P<0.001; adjusted HR=2.19 (95%CI 1.62-2.97)). For questionnaire survey on the reasons for not receiving a vaccination, 115 questionnaires were distributed and 112 valid questionnaires (97.4%) were collected. The main reasons for not being vaccinated were that parents thought that their children were not in the range of appropriate age for vaccination (51 cases, 45.5%) and children were in special physical conditions (47 cases, 42.0%). Conclusion: Vaccination can effectively shorten the negative conversion time of children with COVID-19 and targeted programs should be developed to increase eligible children's vaccination rate for SARS-CoV-2 vaccination.


Asunto(s)
COVID-19 , Vacunas , Niño , Femenino , Masculino , Humanos , COVID-19/prevención & control , Vacunas contra la COVID-19 , Estudios Retrospectivos , SARS-CoV-2 , China/epidemiología
4.
Zhonghua Yu Fang Yi Xue Za Zhi ; 55(7): 805-810, 2021 Jul 06.
Artículo en Chino | MEDLINE | ID: mdl-34304415

RESUMEN

Birth defects and rare diseases are serious challenges in China and even in the world, and most of them lack effective treatment. Preimplantation genetic testing (PGT) prevents the occurrence of this kind of disease at the source by carrying out genetic testing in the preimplantation stage and selecting normal embryos for transplantation. In this paper, the methods of PGT for birth defects and rare diseases and their latest progress are described.


Asunto(s)
Diagnóstico Preimplantación , Aneuploidia , China , Femenino , Fertilización In Vitro , Pruebas Genéticas , Humanos , Embarazo , Enfermedades Raras/genética , Enfermedades Raras/prevención & control
5.
Artículo en Chino | MEDLINE | ID: mdl-33036531

RESUMEN

Objective: To connect with the measurement data of asbestos dust fiber concentration in foreign countries, improve the accuracy of asbestos fiber detection in China, and understand the dust exposure in the working environment of asbestos and man-made mineral fiber production and processing sites in Zhejiang Province. The fiber count concentrations of working environment in glass fiber, ceramic fiber and asbestos processing plants were measured and compared. Methods: The dust concentration in the working environment of two glass fiber factories, one ceramic fiber factory and eight asbestos products processing factories was measured. The total dust mass concentration was measured according to GBZ/T 192.1-2007, and the fiber count concentration was measured by phase contrast microscope. Kruskal Wallis was used to test and compare the dust concentration in the working environment of each post. The correlation between asbestos mass concentration and fiber count concentration was analyzed by Spearman correlation. Results: Under the phase contrast microscope, there were many short and fine asbestos fibers in the field of vision, and there were many impurities around. The average dust concentration of asbestos processing plant was 3.2 f/ml, and the dust concentration of cotton ginning was the highest (6.68 f/ml) . There was a significantly positive correlation between asbestos fiber count concentration and mass concentration (r=0.535, P=0.033) . The average fiber count concentration of glass fiber factory was 0.001 f/ml, and the highest was 0.005 f/ml. The average fiber count concentration of ceramic fiber factory was 0.001 f/ml, and the highest was 0.006 f/ml. Conclusion: The fiber count concentration in the working environment of asbestos factory in Zhejiang Province is obviously over the standard, which is one of the important reasons for the high incidence of mesothelioma in this area. Short and small asbestos fibers are easy to be ignored when counting. It is necessary to improve the actual operation process of fiber counting to form a laboratory standard in China.


Asunto(s)
Amianto , Mesotelioma , Amianto/análisis , China , Polvo/análisis , Humanos , Fibras Minerales/análisis
6.
Beijing Da Xue Xue Bao Yi Xue Ban ; 52(4): 701-704, 2020 Aug 18.
Artículo en Chino | MEDLINE | ID: mdl-32773805

RESUMEN

OBJECTIVE: To evaluate the performance of 3.0T magnetic resonance imaging examination (MRI) for the local detecting of muscle invasive bladder cancer following transurethral resection of bladder tumor (TURBT). METHODS: Retrospective study identified 55 patients with pathology-proven bladder cancer who underwent transurethral resection of bladder tumor followed by 3.0T magnetic resonance imaging between September 2012 and April 2019 in our hospital. Two radiologists reviewed pelvic magnetic resonance imaging together and judged muscle invasive bladder cancer. Sensitivity, specificity and accuracy were calculated for the presence of muscle invasion by T2 weighted imaging (T2WI) only, diffusion-weighted imaging (DWI) only and T2WI+DWI compared with the findings at radical cystectomy as the reference standard. RESULTS: Of the 55 patients with pathological results from radical cystectomy, 3.64% (2/55) had no residual disease; 29.09% (16/55) were non-muscle invasive bladder cancer on pathology, including 13 cases in T1 and 3 cases in Ta; 34.55% (19/55) were in stage T2 depending on pathology, 25.45% (14/55) in T3, and 7.27% (4/55) in T4. The average age was 60.76 years, ranging from 42 to 82 years. There were 48 males and 7 females in our study. Before pelvic MRI examination, all the patients received transurethral resection of bladder tumor, including 16 cases taking the operation in our hospital and 39 cases in other hospitals. The interval between the pelvic MRI examination and transurethral resection of bladder tumor was more than 2 weeks in all the patients. They all underwent radical cystectomy within 1 month after the pelvic MRI examination, and no patient underwent radiotherapy or chemotherapy in our study during the interval between the MRI examination and radical cystectomy. T2WI only, DWI only, and T2WI+DWI of 3.0T magnetic resonance imaging for readers were with sensitivity: 94.59%, 83.78%, 91.89%; with specificity: 66.67%, 77.78%, 72.22% and with accuracy: 85.45%, 81.82%, 85.45%, respectively. CONCLUSION: 3.0T MRI may have a role in diagnosing muscle invasive bladder cancer following TURBT. T2WI has the advantage of detecting the location of bladder tumor, and DWI has the advantage of differentiating between the benign and malignant lesion. 3.0T MRI T2WI+DWI has a good utility in the detection of muscle invasive bladder cancer following TURBT with satisfied accuracy.


Asunto(s)
Neoplasias de la Vejiga Urinaria , Adulto , Anciano , Anciano de 80 o más Años , Cistectomía , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Retrospectivos , Neoplasias de la Vejiga Urinaria/diagnóstico por imagen
7.
Eur Rev Med Pharmacol Sci ; 24(12): 6931-6938, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32633386

RESUMEN

OBJECTIVE: To explore the associations of interleukin-18 (IL-18) and IL-9 gene polymorphisms with susceptibility to asthma, and to study the associations between IL-18 and IL-9 expression levels and polymorphisms. PATIENTS AND METHODS: A total of 200 asthma patients in our hospital were collected as disease group, while 200 healthy people were taken as control group. The deoxyribonucleic acid (DNA) was extracted from peripheral blood and sent to the company for the detection of IL-18 and IL-9 gene polymorphisms via sequencing. The levels of serum IL-18 and IL-9 were determined using enzyme-linked immunosorbent assay (ELISA), and arterial blood gas analysis was performed for patients. RESULTS: The allele distributions at IL-18 gene loci rs189667 and rs360715 had no differences between control group and disease group. The allele distributions at IL-9 gene loci rs1859430 and rs2066758 were different between the two groups (p=0.001, p=0.022), among which the G allele frequency was the highest in disease group [245 (0.613)], and the T allele frequency was also the highest in disease group [240 (0.600)]. There was a difference in the genotype distribution at IL-9 gene locus rs1859430 between the two groups, and the GG genotype frequency in disease group [82 (0.410)] was significantly higher than that in control group (p=0.005). The CC genotype frequency at rs2066758 was significantly lower in disease group [27 (0.135), p=0.044]. In disease group, the frequency of heterozygous model CT (p=0.047) at IL-18 gene locus rs360715, and recessive model GA+AA (p=0.021) and heterozygous model GA (p=0.031) at IL-19 gene locus rs1859430 was significantly lower than that in control group. In disease group, the AC haplotype frequency at IL-18 gene loci rs189667 and rs360715 was evidently lower than that in control group (p=0.048). Disease group had evidently lower AT haplotype frequency (p=0.006) and evidently higher GT haplotype frequency (p=0.000) at IL-9 gene loci rs1859430 and rs2066758. Moreover, the level of serum IL-18 in patients with TT genotype at IL-18 gene locus rs360715 was higher than that in those with other genotypes in disease group (p<0.05), and the level of serum IL-9 in patients with AG genotype at IL-9 gene locus rs1859430 was also higher than that in those with other genotypes in disease group (p<0.05). There was a remarkable association between CT genotype at IL-18 gene locus rs360715 and partial pressure of oxygen (PaO2) (p=0.035), and between CC genotype at IL-9 gene locus rs2066758 and partial pressure of carbon dioxide (PaCO2) (p=0.041). CONCLUSIONS: The expression levels of serum IL-18 and IL-9 and their gene polymorphisms are significantly associated with asthma.


Asunto(s)
Asma/genética , Interleucina-18/genética , Interleucina-9/genética , Polimorfismo Genético/genética , Adulto , Asma/diagnóstico , Humanos
8.
Eur Rev Med Pharmacol Sci ; 23(12): 5382-5391, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31298391

RESUMEN

OBJECTIVE: Acute lung injury (ALI) is the most common complication of severe acute pancreatitis (SAP) in the early stage, which causes systemic inflammatory response and organ damage. Human runt-associated transcription factor 3 gene (RUNX3) has been reported to participate in various inflammatory diseases. However, the exact role of RUNX3 in SAP and its-related ALI remains unclear. MATERIALS AND METHODS: To establish the model of SAP, rats were retrogradely injected with 5% sodium taurocholate (1 mg/kg body weight) into the biliary-pancreatic duct. Cytokine level in serum was measured by ELISA, and the polymorphonuclear neutrophil (PMN) was isolated from rat's blood 12 h-post SAP induction. RESULTS: We found RUNX3 expression was significantly decreased with the progression of SAP. Both pancreas damages and cytokine production abilities were reduced in RUXN3-overexpressed SAP rats compared with control rats. Moreover, SAP-associated ALI was also improved upon RUNX3 overexpression in SAP rats. RUNX3 upregulation enhanced PMN apoptosis and inhibited Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) phosphorylation. CONCLUSIONS: Our study indicates that RUNX3 protects against SAP and SAP-associated ALI through controlling PMN apoptosis and regulating JAK2/STAT3 signaling pathway. RUNX3 could be regarded as a potent therapeutic target in SAP for future studies.


Asunto(s)
Lesión Pulmonar Aguda/inmunología , Neutrófilos/inmunología , Pancreatitis/complicaciones , Transducción de Señal/inmunología , Lesión Pulmonar Aguda/diagnóstico , Lesión Pulmonar Aguda/patología , Amilasas/sangre , Animales , Apoptosis/inmunología , Lavado Broncoalveolar , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/inmunología , Subunidad alfa 3 del Factor de Unión al Sitio Principal , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Humanos , Janus Quinasa 2/metabolismo , Masculino , Neutrófilos/metabolismo , Pancreatitis/inducido químicamente , Pancreatitis/diagnóstico , Pancreatitis/inmunología , Fosforilación/inmunología , Ratas , Factor de Transcripción STAT3/metabolismo , Índice de Severidad de la Enfermedad , Ácido Taurocólico/administración & dosificación , Ácido Taurocólico/toxicidad
9.
Eur Rev Med Pharmacol Sci ; 23(2): 699-707, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30720177

RESUMEN

OBJECTIVE: We aimed to detect the role and function of microRNA-431 (miR-431) in lung cancer, and to investigate the underlying mechanism in regulating the development of lung cancer. PATIENTS AND METHODS: Quantitative Real-time polymerase chain reaction (qRT-PCR) was utilized to measure the relative expression level of miR-431 in lung cancer tissues and cell lines. Cell counting kit-8 (CCK-8) and colony formation assays were employed to measure the proliferative ability of lung cancer cells. Meanwhile, transwell assay was recruited to detect the invasive and migratory abilities of lung cancer cells. Furthermore, dual-luciferase reporter gene assay was designed to verify the target gene of miR-431. Western blot assay was used to gauge the protein level of DDX5 (DEAD box polypeptide 5). RESULTS: MiR-431 expression was significantly lower in 122 lung cancer tissue samples or cell lines compared to the adjacent normal tissues or lung bronchial epithelial cell line, respectively. Over-expression of miR-431 significantly inhibited proliferation, invasion and migration of A549 cells. Down-regulation of miR-431 accelerated cell growth and metastasis of H1650 cells. DDX5 was proved to be a direct target for miR-431 in lung cancer. CONCLUSIONS: MiR-431 expression decreased in lung cancer tissues and cells. MiR-431 suppressed proliferation, invasion and migration of lung cancer cells via inhibiting the expression of DDX5. Our study might provide a novel target for the biological therapy of lung cancer.


Asunto(s)
ARN Helicasas DEAD-box/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/genética , MicroARNs/metabolismo , Células A549 , Movimiento Celular/genética , Proliferación Celular/genética , Regulación hacia Abajo , Técnicas de Silenciamiento del Gen , Humanos , Pulmón/patología , Pulmón/cirugía , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , MicroARNs/genética , Invasividad Neoplásica/genética , Neumonectomía
10.
Eur Rev Med Pharmacol Sci ; 22(18): 5906-5913, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-30280771

RESUMEN

OBJECTIVE: To investigate the difference in expression level of hepatitis B virus (HBV) X gene, and to further study the difference of HBV X protein (HBx) at varied expression levels in apoptosis regulation of hepatocellular carcinoma cells. The recombinant plasmid rPX with HBV enhancer 1 (Enh1), X gene promoter, X gene and polyA tail were constructed, respectively. PATIENTS AND METHODS: HepG2 cells were transiently transfected with the recombinant plasmids and control vector pGEM®-7Zf (+) by virtue of Fugene®HD; reverse transcription PCR (RT-PCR) and Western blotting were applied to analyze the transcription and expression of HBV X gene as well as the difference in the expression level in multiple groups. The activity of the transfected cells in each group was detected by using the methyl thiazolyl tetrazolium (MTT) method for 6 consecutive days after transfection. A flow cytometer was utilized to measure the cell apoptosis rate. RESULTS: The RT-PCR results showed that messenger RNA expression of HBV X gene was detected in all HepG2 cells transfected by different recombinant plasmids, of which the relationships of the expression levels were rCX>rEX1 and rEX2> rPX (p<0.05). Only HepG2/rCX cells in each group of transfected cells showed HBx expression by Western blot. MTT method revealed that there were notable differences between HepG2/rCX, HepG2/rEX1, HepG2/rPX and HepG2/pGEM®-7Zf (+) (p<0.05). The apoptosis rates of HepG2/rCX, HepG2/rEX1 and HepG2/rPX were significantly higher than that of HepG2/pGEM®-7Zf (+) (p<0.05). CONCLUSIONS: HBx can promote cell apoptosis. Results of this research also indicate that there is a significant difference in the pro-apoptotic role of HBx when its expression is regulated by different promoters, and such a difference may be a part of the complex pathogenic mechanisms of HBV and hepatocellular carcinoma.


Asunto(s)
Carcinoma Hepatocelular/metabolismo , Virus de la Hepatitis B/metabolismo , Neoplasias Hepáticas/metabolismo , Transactivadores/metabolismo , Apoptosis , Carcinoma Hepatocelular/genética , Regulación Neoplásica de la Expresión Génica , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Plásmidos/genética , Regiones Promotoras Genéticas , Transactivadores/genética , Transfección , Proteínas Reguladoras y Accesorias Virales
12.
Zhonghua Yi Xue Za Zhi ; 97(7): 496-501, 2017 Feb 21.
Artículo en Chino | MEDLINE | ID: mdl-28260287

RESUMEN

Objective: To discuss the value of RESOLVE for predicting early therapeutic effect of concourrent radiochemotherapy in advanced stage nasopharngeal carcinoma patients. Methods: Sixty-eight patients with nasopharyngeal carcinoma were confirmed by pathology in Henan Cancer Hospital from June 2014 to January 2016.All patients underwent RESLOVE(b value=800 s/mm(2)) with a 3.0 T MRI scanner.The ADC value and the area of the tumor was measured before treatment and 2 weeks after treatment independently performed by two radiologists with 5 years experiences and the agreement evaluation was performed using ANOVA analysis.The correlation among pretreatment ADC value, pathology type, gender, tumor area and the tumor regression rate were analyzed using Spearman rank correlation test.The difference between pretreatment ADC value was compared in CR group and non-CR group by independent sample t test.ROC curve was drawn and the maximum Youden index value was the cutoff calculating the ADC value and predicting the sensitivity, specificity and area under the curve. Results: (1)The agreement between 2 radiologist was excellent. The ICC values of the ADC and the area of the tumor before treatment and the area of the tumor after treatment were 0.89, 0.92 and 0.95, respectively. (2)The pretreatment ADC values of the CR group and the non-CR group were (0.877±0.103)×10(-3) mm(2)/s and (0.779±0.078)×10(-3) mm(2)/s, respectively. There was statistical difference t value=2.874, P value=0.005.(3)ROC curve showed that the sensitivity and specificity of the pretreatment ADC value in predicting CR was 85.2% and 71.0%, with the cut-off value of 0.792×10(-3) mm(2)/s, and the area under curve was 0.778.(4)There was apparently correlation beween the pretreatment ADC value and the tumor regression rate(r=0.333, P=0.006). There was no correlation among pretreatment ADC value, pathology type, gender and tumor area (P>0.05). Conclusion: There is important value using the pretreatment ADC value measured by RESOLVE for predicting the early effect of concurrent radiochemotherapy in advanced stage nasopharngeal carcinoma patients.


Asunto(s)
Quimioradioterapia , Imagen de Difusión por Resonancia Magnética , Carcinoma , Humanos , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Curva ROC
14.
Genet Mol Res ; 14(4): 17708-17, 2015 Dec 22.
Artículo en Inglés | MEDLINE | ID: mdl-26782416

RESUMEN

Despite recent advances in osteosarcoma diagnosis and therapy, much remains unclear about the molecular mechanisms involved in the disorder, and the discovery of novel drug-targeted genes is essential. We explored the potential molecular mechanisms and target genes involved in the development and progression of osteosarcoma. First, we identified the differentially expressed genes in osteosarcoma patients and matching normal controls. We then constructed a differential expression network based on differential and non-differential interactions. Pathway-enrichment analysis was performed based on the nodes contained in the main differential expression network. Centrality analysis was used to select hub genes that may play vital roles in the progression of human osteosarcoma. Our research revealed a total of 176 differentially expressed genes including 82 upregulated and 94 downregulated genes. A differential expression network was constructed that included 992 gene pairs (1043 nodes). Pathway-enrichment analysis indicated that the nodes in the differential expression network were mainly enriched in several pathways such as those involved in cancer, cell cycle, ubiquitin-mediated proteolysis, DNA replication, ribosomes, T-cell receptor signaling, spliceosomes, neurotrophin signaling, oxidative phosphorylation, and tight junctions. Six hub genes (APP, UBC, CAND1, RPA, YWHAG, and NEDD8) were discovered; of these, two genes (UBC and RPA) were also found to be disease genes. Our study predicted that UBC and RPA had potential as target genes for the diagnosis and treatment of osteosarcoma.


Asunto(s)
Antígenos de Neoplasias/biosíntesis , Neoplasias Óseas/genética , Osteosarcoma/genética , Proteína de Replicación A/biosíntesis , Adulto , Anciano , Antígenos de Neoplasias/genética , Neoplasias Óseas/patología , Ciclo Celular/genética , Línea Celular Tumoral , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/biosíntesis , Proteínas de Neoplasias/genética , Osteoblastos/metabolismo , Osteosarcoma/patología , Proteína de Replicación A/genética , Transducción de Señal/genética
15.
Cell Death Dis ; 5: e1085, 2014 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-24577083

RESUMEN

Inhibitor-of-apoptosis protein (IAP) inhibitors have been reported to synergistically reduce cell viability in combination with a variety of chemotherapeutic drugs via targeted cellular IAP (cIAP) depletion. Here, we found that cIAP silencing sensitised colorectal cancer (CRC) cells to selenite-induced apoptosis. Upon selenite treatment, the K63-linked ubiquitin chains on receptor-interacting protein 1 (RIP1) were removed, leading to the formation of the death-inducing complex and subsequent caspase-8 activation. Although the ubiquitinases cIAP1 and cIAP2 were significantly downregulated after a 24-h selenite treatment, cylindromatosis (CYLD) deubiquitinase protein levels were marginally upregulated. Chromatin immunoprecipitation assays revealed that lymphoid enhancer factor-1 (LEF1) dissociated from the CYLD promoter upon selenite treatment, thus abolishing suppression of CYLD gene expression. We corroborated these findings in a CRC xenograft animal model using immunohistochemistry. Collectively, our findings demonstrate that selenite caused CYLD upregulation via LEF1 and cIAP downregulation, both of which contribute to the degradation of ubiquitin chains on RIP1 and subsequent caspase-8 activation and apoptosis. Importantly, our results identify a LEF1-binding site in the CYLD promoter as a potential target for combinational therapy as an alternative to cIAPs.


Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Neoplasias Colorrectales/tratamiento farmacológico , Proteínas Inhibidoras de la Apoptosis/metabolismo , Factor de Unión 1 al Potenciador Linfoide/metabolismo , Proteínas de Complejo Poro Nuclear/metabolismo , Proteínas de Unión al ARN/metabolismo , Ácido Selenioso/farmacología , Proteínas Supresoras de Tumor/metabolismo , Animales , Proteína 3 que Contiene Repeticiones IAP de Baculovirus , Sitios de Unión , Caspasa 8/genética , Caspasa 8/metabolismo , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Enzima Desubiquitinante CYLD , Activación Enzimática , Regulación Neoplásica de la Expresión Génica , Células HCT116 , Humanos , Proteínas Inhibidoras de la Apoptosis/genética , Factor de Unión 1 al Potenciador Linfoide/genética , Ratones , Ratones Desnudos , Regiones Promotoras Genéticas , Interferencia de ARN , Transducción de Señal , Factores de Tiempo , Transfección , Carga Tumoral/efectos de los fármacos , Proteínas Supresoras de Tumor/genética , Ubiquitina-Proteína Ligasas , Ubiquitinación , Ensayos Antitumor por Modelo de Xenoinjerto
16.
Clin Radiol ; 69(2): 194-9, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24290780

RESUMEN

AIM: To evaluate the utility of the elastic ratio calculated using real-time tissue elastography for assessing liver fibrosis in patients with chronic hepatitis B (CHB). MATERIALS AND METHODS: Ninety-six patients with CHB were enrolled between September 2012 and August 2013. The elastic ratio of the liver for the intrahepatic venous small vessel was calculated to measure liver stiffness. Diagnostic performance of the elastic ratio and aminotransferase-to-platelet ratio index (APRI) were compared with histological fibrosis stage at liver biopsy. In addition, 45 healthy adult volunteers were participated in intra- and interobserver reliability studies. RESULTS: There was no significant influence of hepatitis B e antigen (HBeAg) status or hepatitis B virus DNA levels on the elastic ratio measurements in CHB patients. The elastic ratio was significantly correlated with histological fibrosis stage (r = 0.873, p < 0.001). Cut-off values were 2.62 for stage 2 and over (S ≥ 2), 3.20 for state 3 and over, and 3.86 for stage 4, respectively. The areas under the receiver operating characteristic (ROC) curves for elastic ratio and APRI diagnosis of significant fibrosis (S ≥ 2) was 0.91 (95% CI: 0.84-0.98) and 0.71 (95% CI: 0.57-0.86), and 0.94 (95% CI: 0.89-0.99) and 0.81 (95% CI: 0.71-0.91) for cirrhosis (S = 4), respectively. The elastic ratio measurements had good reproducibility: 0.838 for intra-observer reliability and 0.805 for inter-observer reliability, respectively (p < 0.001). CONCLUSION: Elastic ratio determined using real-time tissue elastography was an accurate and reproducible method for evaluating liver fibrosis in patients with CHB.


Asunto(s)
Diagnóstico por Imagen de Elasticidad/métodos , Hepatitis B Crónica/diagnóstico por imagen , Cirrosis Hepática/diagnóstico por imagen , Adolescente , Adulto , Anciano , Área Bajo la Curva , Femenino , Hepatitis B Crónica/complicaciones , Humanos , Hígado/diagnóstico por imagen , Cirrosis Hepática/etiología , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Curva ROC , Reproducibilidad de los Resultados , Adulto Joven
17.
Cell Death Dis ; 4: e973, 2013 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-24357804

RESUMEN

It has previously been shown that selenite can act as an antitumor agent and inhibit cancer cell growth, although the mechanism responsible for this effect is not well understood. In this study, we have shown that selenite can induce cell cycle arrest and apoptosis in NB4 cells. Selenite treatment of these cells also inhibited the JNK/ATF2 axis. Further experiments demonstrated that selenite-induced production of reactive oxygen species (ROS) worked as an upstream of the JNK/ATF2 axis, cell cycle arrest and apoptosis. Inactivation of ATF2 resulted in decreased affinity of this transcription factor for the promoters of cyclin A, cyclin D3 and CDK4, which led to the arrest of the NB4 cells in the G0/G1 phase. Finally, in vivo experiments confirmed the antitumor activity of selenite and the mechanisms that were described in vitro. Taken together, our results indicate that selenite-induced ROS arrest NB4 cells at G0/G1 phase through inhibiting the JNK/ATF2 axis in vitro and in vivo.


Asunto(s)
Factor de Transcripción Activador 2/metabolismo , Apoptosis/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Ácido Selenioso/farmacología , Factor de Transcripción Activador 2/genética , Animales , Línea Celular , Femenino , Humanos , Inmunohistoquímica , Etiquetado Corte-Fin in Situ , Sistema de Señalización de MAP Quinasas/genética , Ratones , Ratones Desnudos
18.
J Med Microbiol ; 62(Pt 12): 1864-1867, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24008500

RESUMEN

Chlamydia are Gram-negative obligate bacteria that cause a wide range of diseases in humans and animals. To assess the risk of zoonosis posed by pigs, a total of 920 serum samples were collected from pigs in 11 administrative cities in Jiangxi province, south-eastern China, and the seroprevalence of Chlamydia antibodies was investigated by an indirect haemagglutination assay. The pathogen-specific antibodies were detected in 539 (58.59 %) pigs with seroprevalence ranging from 33.33 % (Jingdezhen) to 90.91 % (Pingxiang) among different cities (P<0.05). The highest prevalence was found in pregnant sows (80.89 %, 127/157), followed by breeding boars (79.37 %, 50/63), suckling sows (77.01 %, 67/87), fattening pigs (69.32 %, 61/88) and non-pregnant sows (62.5 %, 180/288). Piglets had the lowest prevalence of 22.78 % (54/237). The seroprevalence of Chlamydia infection among different categories of pigs was also significantly different (P<0.05). These results indicate that Chlamydia is highly prevalent in pigs in Jiangxi province and our results indicate that the presence of Chlamydia exposure in pigs may pose a potential threat to human health.


Asunto(s)
Infecciones por Chlamydia/epidemiología , Infecciones por Chlamydia/inmunología , Chlamydia/inmunología , Animales , Anticuerpos Antibacterianos/inmunología , China/epidemiología , Infecciones por Chlamydia/microbiología , Pruebas de Hemaglutinación/métodos , Prevalencia , Estudios Seroepidemiológicos , Porcinos , Zoonosis/epidemiología , Zoonosis/inmunología , Zoonosis/microbiología
19.
Cancer Gene Ther ; 20(8): 453-60, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23928732

RESUMEN

Mammalian STE20-like kinase 1 (Mst1) ubiquitously encodes serine threonine kinase, which is a 59-kDa class II GC kinase that shares 76% identity in amino-acid sequence with MST2, and is the closest mammalian homolog of Drosophila Hippo protein kinase, a major inhibitor of cell proliferation in Drosophila. Recent studies have shown that Mst1 and Mst2 perform tumor-suppressor function in a redundant manner and were originally identified as pro-apoptotic cytoplasmic kinases important for controlling cell growth, proliferation, apoptosis and organ size. We used recombinant eukaryotic expression vector containing human wild-type Mst1 gene to transfect human non-small cell lung cancer (NSCLC) A549 cells in vitro and in vivo. The results showed that Mst1 overexpression inhibited cell proliferation and induced apoptosis of A549 cells, promoted Yes-associated protein (YAP) (Ser127) phosphorylation and downregulated the transcriptional level of Cystein-rich protein connective tissue growth factor (CTGF), amphiregulin (AREG) and Survivin. In human NSCLC-cell-A549-xenograft models, Mst1 gene or cisplatin alone suppressed the growth of tumors and increased the cytoplasm-positive expression levels of YAP and Phospho-YAP (Ser127) proteins; however, their combination had the strongest anticancer effects. Overall, Mst1 has an important role in inhibiting the growth of NSCLC in vitro and in vivo; its antiproliferative effect is associated with induction of apoptosis through promotion of the cytoplasmic localization and phosphorylation of YAP protein at Ser127 site, indicating that Mst1 may be developed as a promising therapeutic target for NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/enzimología , Neoplasias Pulmonares/enzimología , Proteínas Serina-Treonina Quinasas/biosíntesis , Secuencia de Aminoácidos , Anfirregulina , Animales , Apoptosis/fisiología , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Procesos de Crecimiento Celular/fisiología , Factor de Crecimiento del Tejido Conjuntivo/biosíntesis , Factor de Crecimiento del Tejido Conjuntivo/genética , Familia de Proteínas EGF , Femenino , Técnicas de Transferencia de Gen , Glicoproteínas/biosíntesis , Glicoproteínas/genética , Xenoinjertos , Humanos , Proteínas Inhibidoras de la Apoptosis/biosíntesis , Proteínas Inhibidoras de la Apoptosis/genética , Péptidos y Proteínas de Señalización Intercelular/biosíntesis , Péptidos y Proteínas de Señalización Intercelular/genética , Péptidos y Proteínas de Señalización Intracelular , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Datos de Secuencia Molecular , Proteínas Serina-Treonina Quinasas/genética , Transducción de Señal , Survivin , Transfección
20.
Cell Death Dis ; 4: e708, 2013 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-23828571

RESUMEN

RhoA GTPase dysregulation is frequently reported in various tumours and haematologic malignancies. RhoA, regulating Rho-associated coiled-coil-forming kinase 1 (ROCK1), modulates multiple cell functions, including malignant transformation, metastasis and cell death. Therefore, RhoA/ROCK1 could be an ideal candidate target in cancer treatment. However, the roles of RhoA/ROCK1 axis in apoptosis of leukaemia cells remain elusive. In this study, we explored the effects of RhoA/ROCK1 cascade on selenite-induced apoptosis of leukaemia cells and the underlying mechanism. We found selenite deactivated RhoA/ROCK1 and decreased the association between RhoA and ROCK1 in leukaemia NB4 and Jurkat cells. The inhibited RhoA/ROCK1 signalling enhanced the phosphorylation of Erk1/2 in a Mek1/2-independent manner. Erk1/2 promoted apoptosis of leukaemia cells after it was activated. Intriguingly, it was shown that both RhoA and ROCK1 were present in the multimolecular complex containing Erk1/2. GST pull-down analysis showed ROCK1 had a direct interaction with GST-Erk2. In addition, selenite-induced apoptosis in an NB4 xenograft model was also found to be associated with the RhoA/ROCK1/Erk1/2 pathway. Our data demonstrate that the RhoA/ROCK1 signalling pathway has important roles in the determination of cell fates and the modulation of Erk1/2 activity at the Mek-Erk interplay level.


Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Ácido Selenioso/farmacología , Quinasas Asociadas a rho/metabolismo , Proteína de Unión al GTP rhoA/fisiología , Animales , Caspasa 3/metabolismo , Caspasa 9/metabolismo , Activación Enzimática/efectos de los fármacos , Humanos , Células Jurkat , Leucemia Promielocítica Aguda/tratamiento farmacológico , Sistema de Señalización de MAP Quinasas , Masculino , Ratones , Ratones Desnudos , Terapia Molecular Dirigida , Fosforilación , Procesamiento Proteico-Postraduccional , Ensayos Antitumor por Modelo de Xenoinjerto
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