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1.
Medicine (Baltimore) ; 100(1): e23355, 2021 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-33429729

RESUMEN

ABSTRACT: Brain magnetic resonance imaging (MRI) white matter lesions have been reported in some preoperative cochlear implant children. However, the role of white matter lesions in predicting the hearing outcome is yet unclear. The present study investigated the outcomes of cochlear implantation (CI) in 40 children with white matter lesions.The data from children with white matter lesions were reviewed in this retrospective study. Based on brain MRI, the patients were divided into 3 groups: mild, moderate, and severe. The children were treated with unilateral CI and monitored for a follow-up period of at least 3 years. The main outcome measures were category of auditory performance (CAP) and speech intelligibility rating (SIR). MRI white matter lesions, age at implant, gender, physical impairment, and cognitive impairment were obtained from a research database to assess the correlation with long-term CAP and SIR outcome by multiple regression analysis.The data of children with white matter lesions were reviewed (18 females and 23 males). The mean age at implantation was 31.6 months. Strikingly, all children obtained better CAP and SIR scores. The age at implantation, brain white matters lesions on MRI, and cognitive and physical disabilities were associated with CAP and SIR scores. Multiple regression established a weak correlation between the degree of white matter lesions on brain MRI and long-term CAP and SIR, while cognitive impairment strongly accounted for long-term CAP and SIR outcome.The majority of the children with brain white matter lesions obtained a satisfactory postoperative effect. The cognitive impairment before CI is a major factor, and such factor should be considered.


Asunto(s)
Implantación Coclear/normas , Pérdida Auditiva/clasificación , Leucoencefalopatías/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Implantación Coclear/métodos , Implantación Coclear/rehabilitación , Femenino , Pérdida Auditiva/cirugía , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Análisis de Regresión , Sustancia Blanca/anomalías , Sustancia Blanca/lesiones , Sustancia Blanca/fisiopatología
2.
Braz J Med Biol Res ; 53(12): e9174, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33111743

RESUMEN

We aimed to investigate the association of long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (lnc-MALAT1) with acute ischemic stroke (AIS), and its association with disease severity, inflammation, and recurrence-free survival (RFS) in AIS patients. One hundred and twenty AIS patients and 120 controls were recruited. Venous blood samples from AIS patients (within 24 h after symptoms onset) and controls (at entry to study) were collected to detect plasma lnc-MALAT1 expression by real-time quantitative polymerase chain reaction. AIS severity was assessed by the National Institutes of Health Stroke Scale (NIHSS) score. Plasma concentrations of inflammation factors (including C-reactive protein (CRP), tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-8, IL-10, IL-17, and IL-22) were measured and RFS was calculated. lnc-MALAT1 expression was decreased in AIS patients compared to controls, and it had a close correlation with AIS (AUC=0.791, 95% CI: 0.735-0.846). For disease condition, lnc-MALAT1 expression negatively correlated with NIHSS score and pro-inflammatory factor expression (including CRP, TNF-α, IL-6, IL-8, and IL-22), while it positively correlated with anti-inflammatory factor IL-10 expression. Furthermore, lnc-MALAT1 expression was elevated in AIS patients with diabetes. For prognosis, no statistical correlation of lnc-MALAT1 expression with RFS was found, while a trend for longer RFS was observed in patients with lnc-MALAT1 high expression compared to those with lnc-MALAT1 low expression.

3.
Braz. j. med. biol. res ; 53(12): e9174, 2020. tab, graf
Artículo en Inglés | LILACS-Express | LILACS, Coleciona SUS | ID: biblio-1132510

RESUMEN

We aimed to investigate the association of long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (lnc-MALAT1) with acute ischemic stroke (AIS), and its association with disease severity, inflammation, and recurrence-free survival (RFS) in AIS patients. One hundred and twenty AIS patients and 120 controls were recruited. Venous blood samples from AIS patients (within 24 h after symptoms onset) and controls (at entry to study) were collected to detect plasma lnc-MALAT1 expression by real-time quantitative polymerase chain reaction. AIS severity was assessed by the National Institutes of Health Stroke Scale (NIHSS) score. Plasma concentrations of inflammation factors (including C-reactive protein (CRP), tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-8, IL-10, IL-17, and IL-22) were measured and RFS was calculated. lnc-MALAT1 expression was decreased in AIS patients compared to controls, and it had a close correlation with AIS (AUC=0.791, 95% CI: 0.735-0.846). For disease condition, lnc-MALAT1 expression negatively correlated with NIHSS score and pro-inflammatory factor expression (including CRP, TNF-α, IL-6, IL-8, and IL-22), while it positively correlated with anti-inflammatory factor IL-10 expression. Furthermore, lnc-MALAT1 expression was elevated in AIS patients with diabetes. For prognosis, no statistical correlation of lnc-MALAT1 expression with RFS was found, while a trend for longer RFS was observed in patients with lnc-MALAT1 high expression compared to those with lnc-MALAT1 low expression.

4.
Dig Dis Sci ; 64(8): 2167-2176, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-30761473

RESUMEN

BACKGROUND: The Tec kinase family is involved in acute and chronic inflammatory diseases, but its relationship with severe acute pancreatitis (SAP) remains unclear. AIMS: To investigate whether Tec tyrosine kinase can be used as a target for severe acute pancreatitis-associated acute lung injury (PALI). METHODS: A total of 90 mice were randomly assigned into four groups: SAP (n = 15), control (n = 15), SAP + α-cyano-ß-hydroxy-ß-methyl-N-(2,5-dibromophenyl)propenamide (LFM-A13) (pretreated with Tec kinase inhibitor LFM-A13, n = 15), and SAP + Tec siRNA (pretreated with PBS/negative control siRNA/Tec siRNA, n = 45). SAP was induced by caerulein and lipopolysaccharide. Animals were sacrificed at 0, 3, 24, 48, and 72 h, respectively. Pathological changes and scores of the lung and pancreas were determined using hematoxylin-eosin staining. Expression of Tec and phosphorylated Tec (p-Tec) were examined by real-time polymerase chain reaction, Western blot, and immunoprecipitation. Serum levels of amylase, myeloperoxidase, and pro-inflammatory cytokines were measured by ELISA. RESULTS: The expression of Tec in lung tissue was significantly higher in the SAP group than in the control group (p < 0.05), and p-Tec expression gradually increased with time. Furthermore, p-Tec expression was significantly lower in the SAP + LFM-A13 group than in the SAP group (p < 0.05); however, Tec expression did not vary. Tec inhibitors, LFM-A13 and Tec siRNA, alleviated pathological damage and release of inflammatory cytokines (p < 0.05). CONCLUSIONS: Tec tyrosine kinase plays a key role in PALI, and is therefore a potential target for clinical treatment.


Asunto(s)
Lesión Pulmonar Aguda/prevención & control , Amidas/farmacología , Antiinflamatorios/farmacología , Pulmón/efectos de los fármacos , Nitrilos/farmacología , Pancreatitis/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Lesión Pulmonar Aguda/enzimología , Lesión Pulmonar Aguda/etiología , Lesión Pulmonar Aguda/patología , Amilasas/sangre , Animales , Citocinas/sangre , Modelos Animales de Enfermedad , Mediadores de Inflamación/sangre , Pulmón/enzimología , Pulmón/patología , Masculino , Ratones Endogámicos C57BL , Infiltración Neutrófila/efectos de los fármacos , Pancreatitis/complicaciones , Pancreatitis/enzimología , Peroxidasa/sangre , Fosforilación , Proteínas Tirosina Quinasas/genética , Proteínas Tirosina Quinasas/metabolismo , Interferencia de ARN , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Transducción de Señal
5.
J Surg Res ; 233: 262-267, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30502258

RESUMEN

BACKGROUND: This study aims to investigate the related factors for the retention time of tracheobronchial foreign bodies in infants and children, to provide help for the assessment of the disease, surgical risk, and prognosis. MATERIALS AND METHODS: The clinical data of 1060 patients with tracheobronchial foreign bodies from January 2015 to December 2015 were retrospectively studied, and the correlation of the retention time of foreign bodies with age, gender, preoperative complications, granulation formation, operation time, and hospital stay was analyzed. RESULTS: The retention time of foreign bodies was not correlated with age (r = 0.041, P = 0.194) and gender (r = 0.039, P = 0.214) but was correlated with preoperative complications (r = 0.072, P = 0.023), granulation formation (r = 0.134, P < 0.001), operation time (r = 0.112, P < 0.001), and hospital stay (r = 0.189, P < 0.001). CONCLUSIONS: The retention time of foreign bodies was closely correlated with granulation formation, preoperative complications, operation time, and hospital stay.


Asunto(s)
Bronquios/lesiones , Cuerpos Extraños/cirugía , Tiempo de Tratamiento/estadística & datos numéricos , Tráquea/lesiones , Bronquios/cirugía , Broncoscopía , Niño , Preescolar , Femenino , Cuerpos Extraños/complicaciones , Cuerpos Extraños/diagnóstico , Humanos , Lactante , Tiempo de Internación/estadística & datos numéricos , Masculino , Tempo Operativo , Periodo Preoperatorio , Estudios Retrospectivos , Distribución por Sexo , Factores de Tiempo , Tráquea/cirugía , Resultado del Tratamiento
6.
Curr Med Sci ; 38(6): 1005-1011, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30536062

RESUMEN

Dasatinib is a second-generation tyrosine kinase inhibitor (TKI) and it could be used as a second-line treatment for patients with chronic myeloid leukemia (CML). Yinishu, a generic dasatinib made in China, was approved by the China Food and Drug Administration in 2013 and it costs much less than the patented dasatinib SPRYCEL. The present study aimed to examine the efficacy and safety of Yinishu as a second-line treatment for CML by comparing the baseline clinical characteristics, rates of adverse events and efficacy between Yinishu and SPRYCEL groups. The results showed that there were no significant differences in the rates of optimal response between Yinishu and SPRYCEL for patients who started second-line treatment because of treatment failure. For patients who started second-line treatment because of intolerance of first-line treatment, their levels of BCR-ABL1/ABL1 on the international scale (BCR-ABLIS) was maintained very low throughout the course of Yinishu treatment. Drug-related adverse events occurred with the same frequency in these two groups. It was confirmed that Yinishu was effective and safe as a secondline treatment for CML patients. Yinishu may be more suitable for patients who are economically unable to pay for the patented dasatinib SPRYCEL.


Asunto(s)
Dasatinib/efectos adversos , Dasatinib/uso terapéutico , Medicamentos Genéricos/efectos adversos , Medicamentos Genéricos/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/uso terapéutico , Adolescente , Adulto , Anciano , Niño , Femenino , Proteínas de Fusión bcr-abl/metabolismo , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/metabolismo , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto Joven
7.
J Thorac Dis ; 10(2): 1037-1042, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-29607178

RESUMEN

Background: This study aims to analyze factors related to the location of tracheobronchial foreign bodies in infants and children, and provide help in the assessment of the disease, surgical risk and prognosis. Methods: The clinical data of 1,060 pediatric patients with tracheobronchial foreign bodies diagnosed from January 2015 to December 2015 were retrospectively studied, the association of the location of the foreign bodies with age, gender, granulation formation, chest computed tomography and 3D reconstruction results, preoperative complications, operation time, and hospital stay was analyzed. Results: The location of foreign bodies was not correlated with age, gender, operation time and length of hospital stay, but was correlated to granulation formation, chest computed tomography and 3D reconstruction results, and preoperative complications. Conclusions: The location of foreign bodies was correlated to granulation formation, the location of foreign bodies displayed by chest computed tomography, and preoperative complications.

8.
Gastrointest Endosc ; 86(3): 519-524.e1, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28062312

RESUMEN

BACKGROUND AND AIMS: Almost all studies on post-ERCP pancreatitis (PEP) have mainly involved patients with biliary diseases rather than chronic pancreatitis (CP), and the concept that CP seems to be a protective factor associated with PEP has not been studied in detail. The aim of this study was to determine the incidence of PEP in patients with CP at different clinical stages and to identify the predictive and protective factors of PEP in a large cohort. METHODS: In this observational cohort study, medical records of patients with CP (CP group) and biliary diseases (BD group) in a tertiary hospital from January 2011 to May 2015 were examined. The difference in the incidence of PEP between CP group and BD group and the risk of PEP at different clinical stages of CP were calculated by the χ2 test or the Fisher exact test. The predictive and protective factors for PEP were investigated by univariate and multivariate analysis. RESULTS: In total, 2028 ERCP procedures were performed in 1301 patients with CP and 2000 procedures in 1655 patients with BD. The overall incidence of PEP in CP group (4.5%) was similar to that in the BD group (4.8%; P = .747). However, CP patients had significantly lower rates of moderate and severe attacks (0% vs 1.3%, P < .01). According to the M-ANNHEIM classification, the PEP incidences of CP at stages 0, I, II, III, and IV were 4.4%, 5.1%, 3.8%, 2.0%, and 2.0%, respectively. CP patients at stage Ia had the highest PEP incidence (8.0%) among all CP patients, significantly higher than that at stages Ib + Ic (3.9%) and II (3.8%). Female gender, history of acute pancreatitis, and prior PEP were independent risk factors of PEP, whereas extracorporeal shock wave lithotripsy was a protective factor. CONCLUSIONS: Compared with BD patients, CP patients had similar incidence of PEP overall but lower grades of severity. The incidence of PEP in CP patients decreased significantly with disease progression. (Clinical trial registration number: NCT02781987.).


Asunto(s)
Enfermedades de las Vías Biliares/cirugía , Colangiopancreatografia Retrógrada Endoscópica , Enfermedades Pancreáticas/cirugía , Pancreatitis/epidemiología , Complicaciones Posoperatorias/epidemiología , Enfermedad Aguda , Adulto , Anciano , China/epidemiología , Estudios de Cohortes , Constricción Patológica/cirugía , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Conductos Pancreáticos , Pancreatitis Crónica , Factores Protectores , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores Sexuales
9.
Exp Ther Med ; 12(5): 3425-3432, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27882174

RESUMEN

Human laryngeal papilloma (LP) is a human papillomavirus-induced hyperplastic tumor of the respiratory tract, which is characterized by rapid growth and apoptosis resistance. Isoflurane (ISO) inhibits proliferation and elicits apoptosis in cancer cells. The results of the present study found that the mRNA and protein levels of cyclooxygenase-2 (COX2) were higher in LP tissues than in normal laryngeal samples, and prostaglandin E2 (PGE2) production was increased in LP cells, as determined by quantitative polymerase chain reaction, western blot and radioimmunoassay analyses. Notably, the increase in COX2 and PGE2 levels was significantly abrogated in the ISO-treated LP cells. The inhibitory effects of ISO on COX2 expression and activity depended on the inactivation of p38 mitogen-activated protein kinase (MAPK) in LP cells. By inhibiting the COX2 activity of LP cells, ISO treatment markedly suppressed cell viability and proliferation, as determined using Cell Counting Kit-8, flow cytometry and 5-ethynyl-20-deoxyuridine incorporation assays. Furthermore, ISO treatment promoted cell apoptosis, as demonstrated by flow cytometry, nucleosomal fragmentation and caspase-3 activity assays. Collectively, the present results suggest that COX2 is critical in the progression of LP, and ISO is a potential agent for LP therapy by impeding p38 MAPK/COX2 signaling.

10.
PLoS One ; 11(8): e0159723, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27532666

RESUMEN

Crossing, backcrossing, and molecular marker-assisted background selection produced a soybean (Glycine max) near-isogenic line (cgy-2-NIL) containing the cgy-2 allele, which is responsible for the absence of the allergenic α-subunit of ß-conglycinin. To identify α-null-related transcriptional changes, the gene expressions of cgy-2-NIL and its recurrent parent DN47 were compared using Illumina high-throughput RNA-sequencing of samples at 25, 35, 50, and 55 days after flowering (DAF). Seeds at 18 DAF served as the control. Comparison of the transcript profiles identified 3,543 differentially expressed genes (DEGs) between the two genotypes, with 2,193 genes downregulated and 1,350 genes upregulated. The largest numbers of DEGs were identified at 55 DAF. The DEGs identified at 25 DAF represented a unique pattern of GO category distributions. KEGG pathway analyses identified 541 altered metabolic pathways in cgy-2-NIL. At 18DAF, 12 DEGs were involved in arginine and proline metabolism. The cgy-2 allele in the homozygous form modified the expression of several Cupin allergen genes. The cgy-2 allele is an alteration of a functional allele that is closely related to soybean protein amino acid quality, and is useful for hypoallergenic soybean breeding programs that aim to improve seed protein quality.


Asunto(s)
Antígenos de Plantas/genética , Regulación de la Expresión Génica de las Plantas/genética , Globulinas/genética , Proteínas de Almacenamiento de Semillas/genética , Semillas/crecimiento & desarrollo , Proteínas de Soja/genética , Soja/genética , Secuencia de Bases , Perfilación de la Expresión Génica , Genes de Plantas/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Fitomejoramiento , Análisis de Secuencia de ARN , Transcriptoma/genética
11.
Burns ; 41(8): 1748-1757, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26514700

RESUMEN

BACKGROUND: Puerarin, the main isoflavone glycoside extracted from the root of Pueraria lobata, is widely prescribed for patients with cardiovascular disorders in China. This study investigates the effect of puerarin on severe burn-induced acute myocardial injury in rats and its underlying mechanisms. MATERIALS AND METHODS: Healthy adult Wistar rats were divided into three groups: (1) sham group, sham burn treatment; (2) burn group, third-degree burns over 30% of the total body surface area (TBSA) with lactated Ringer's solution for resuscitation; and (3) burn plus puerarin group, third-degree burns over 30% of TBSA with lactated Ringer's solution containing puerarin for resuscitation. The burned animals were sacrificed at 1, 3, 6, 12, and 24 h after burn injury. Myocardial injury was evaluated by analyzing serum creatine kinase MB fraction (CK-MB) activity and cardiac troponin T (cTNT) level. Changes in cardiomyocyte ultrastructure were also determined using a transmission electron microscope. Tumor necrosis factor (TNF)-α concentration in serum was measured by radioimmunoassay. Cardiac myeloperoxidase (MPO) activity and malondialdehyde (MDA) concentration were measured to determine neutrophil infiltration and oxidative stress in the heart, respectively. The expression of p38 mitogen-activated protein (MAP) kinase in the heart was determined by Western blot analysis. RESULTS: After the 30% TBSA full-thickness burn injury, serum CK-MB activities and cTnT levels increased markedly, both of which were significantly decreased by the puerarin treatment. The level of serum TNF-α concentration in burn group at each time-point was obviously higher than those in sham group (1.09±0.09 ng/ml), and it reached the peak value at 12 h post burn. Burn trauma also resulted in worsen ultrastructural condition, elevated MPO activity and MDA content in heart tissue, and a significant activation of cardiac p38 MAP kinase. Administration of puerarin improved the ultrastructural changes in cardiomyocytes, decreased TNF-α concentration in serum as well as suppressed cardiac MPO activity and reduced MDA content, and abolished the activation of p38 MAP kinase in heart tissue after severe burn. CONCLUSIONS: These results suggest that puerarin attenuates inflammatory responses, reduces neutrophil infiltration and oxidative stress in the heart, and protects against acute myocardial injury induced by severe burn.


Asunto(s)
Quemaduras/complicaciones , Corazón/efectos de los fármacos , Isoflavonas/farmacología , Isquemia Miocárdica/etiología , Miocardio/inmunología , Infiltración Neutrófila/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Vasodilatadores/farmacología , Animales , Forma MB de la Creatina-Quinasa/sangre , Forma MB de la Creatina-Quinasa/efectos de los fármacos , Inflamación , Malondialdehído/metabolismo , Isquemia Miocárdica/sangre , Miocardio/metabolismo , Peroxidasa/efectos de los fármacos , Peroxidasa/metabolismo , Ratas , Ratas Wistar , Índices de Gravedad del Trauma , Troponina T/sangre , Troponina T/efectos de los fármacos , Proteínas Quinasas p38 Activadas por Mitógenos/efectos de los fármacos , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
12.
Artículo en Inglés | MEDLINE | ID: mdl-26366180

RESUMEN

The main aim of the present study was to assess the antioxidative effects of human umbilical cord-derived mesenchymal stromal cells (UC-MSCs) in a rat model of radiation myelopathy. UC-MSCs were isolated from Wharton's jelly (WJ) of umbilical cords. An irradiated cervical spinal cord rat model (C2-T2 segment) was generated using a (60)Co irradiator to deliver 30 Gy of radiation. UC-MSCs were injected through the tail vein at 90 days, 97 days, 104 days, and 111 days after-irradiation. Histological damage was examined by cresyl violet/Nissl staining. The activities of two antioxidant enzymes catalase (CAT) and glutathione peroxidase (GPX) in the spinal cord were measured by the biomedical assay. In addition, the levels of vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2) in the spinal cord were determined by ELISA methods. Multiple injections of UC-MSCs through the tail vein ameliorated neuronal damage in the spinal cord, increased the activities of the antioxidant enzymes CAT and GPX, and increased the levels of VEGF and Ang-2 in the spinal cord. Our results suggest that multiple injections of UC-MSCs via the tail vein in the rat model of radiation myelopathy could significantly improve the antioxidative microenvironment in vivo.

13.
Artículo en Chino | MEDLINE | ID: mdl-25764929

RESUMEN

OBJECTIVE: To explore the perioperative management of bilateral bronchial foreign bodies in infants to improve the cure rate in the children. METHODS: The medical charts of 45 infants with bilateral bronchial foreign bodies were reviewed. Clinical features and key points to surgery as well as post-operative care were analyzed. RESULTS: All foreign bodies were removed with rigid bronchoscopy under general anesthesia, and 44 of 45 infants were cured with assistance of anti-infective treatments within 3-5 days and one with acute laryngitis and bronchitis was cured through 10-day anti-infective treatment with vancomycin. CONCLUSION: Removal of foreign body by rigid bronchoscopy under general anesthesia is a preferred method to treat bilateral bronchial foreign bodies in infants, to whom early diagnosis, early treatment and postoperative careful care are keys to get a good outcome.


Asunto(s)
Bronquios/cirugía , Cuerpos Extraños/terapia , Periodo Perioperatorio , Anestesia General , Bronquitis , Broncoscopía , Cuerpos Extraños/cirugía , Humanos , Lactante , Tráquea
14.
Oncologist ; 20(3): 263-9, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25657201

RESUMEN

The TERT promoter and FGFR3 gene mutations are two of the most common genetic events in urothelial bladder cancer (UBC), and these mutation assays in patient urine have been shown to be promising biomarkers for UBC diagnosis and surveillance. These results were obtained mainly from studies of patients with UBC in Western countries, and little is known about such information in Han Chinese patients with UBC. In the present study, we addressed this issue by analyzing tumors from 182 Han Chinese patients with UBC and urine samples from 102 patients for mutations in the TERT promoter and FGFR3 and TERT mRNA expression in tumors and/or urine. TERT promoter and FGFR3 mutations were identified in 87 of 182 (47.8%) and 7 of 102 (6.7%) UBC cases, respectively. In 46 urine samples from patients with TERT promoter mutation-carrying tumors, the mutant promoter was detected in 24 (52%) prior to operation and disappeared in most examined urine samples (80%) taken 1 week after operation. TERT mRNA was detected in urine derived from 46 of 49 patients (94%) that was analyzed before operation independently of the presence of TERT promoter mutations. Collectively, FGFR3 mutations occur at a very low rate in Han Chinese UBC and cannot serve as diagnostic markers for Chinese patients. Han Chinese patients with UBC have relatively low TERT promoter mutation frequency compared with patients in Western countries, and simultaneous detection of both mutant TERT promoter and TERT mRNA improves sensitivity and specificity of urine-based diagnosis.


Asunto(s)
Adenocarcinoma/genética , Carcinoma de Células Transicionales/genética , ARN Mensajero/genética , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/genética , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/orina , Telomerasa/genética , Telomerasa/orina , Neoplasias de la Vejiga Urinaria/genética , Adenocarcinoma/patología , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/orina , Carcinoma de Células Transicionales/patología , China/etnología , Femenino , Humanos , Masculino , Mutación , Recurrencia Local de Neoplasia , Reacción en Cadena de la Polimerasa , Regiones Promotoras Genéticas , Sensibilidad y Especificidad , Análisis de Secuencia de ADN , Neoplasias de la Vejiga Urinaria/patología
15.
Oncotarget ; 5(23): 12428-39, 2014 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-25474136

RESUMEN

TERT promoter C228T and C250T mutations occur in various malignancies including bladder cancer (BC) and may serve as urinary tumor markers. However, the mutation association with clinical variables in upper tract urothelial carcinomas (UTUCs) is unclear. There is also a lack of sensitive tools to detect the minor mutant TERT promoter in bulk urinary DNA. Here we analyzed 220 UTUC patients [98 with renal pelvic carcinoma (RPC) and 122 with ureter carcinoma (UC)] and developed a Competitive Allele-Specific TaqMan PCR (castPCR) for urinary assay. We identified C228T or C250T mutations in 42 of 98 (43%) RPC and 23 of 122 (19%) UC tumors. Distant metastases were significantly correlated with UTUC patients harboring TERT promoter mutations (P = 0.001). C228T were detected in 6/10 and 9/10 of urine samples from patients with mutation-carrying tumors using Sanger sequencing and castPCR, respectively. When urine samples from 70 BC patients were analyzed together, the sensitivity of urinary C228T assay was 89% and 50% for castPCR and Sanger sequencing, respectively (P < 0.001). Collectively, TERT promoter mutations occur in UTUCs with a high frequency in RPCs and predict distant metastasis. castPCR assays of the mutation are a useful tool for urine-based diagnostics of urological malignancies.


Asunto(s)
Biomarcadores de Tumor/orina , Carcinoma de Células Transicionales/genética , Neoplasias Renales/genética , Metástasis de la Neoplasia/genética , Telomerasa/genética , Neoplasias Ureterales/genética , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Carcinoma de Células Transicionales/patología , Carcinoma de Células Transicionales/orina , Femenino , Humanos , Neoplasias Renales/patología , Neoplasias Renales/orina , Pelvis Renal/patología , Masculino , Persona de Mediana Edad , Mutación , Metástasis de la Neoplasia/diagnóstico , Reacción en Cadena de la Polimerasa/métodos , Regiones Promotoras Genéticas/genética , Sensibilidad y Especificidad , Neoplasias Ureterales/patología , Neoplasias Ureterales/orina
16.
Oncotarget ; 5(7): 1829-36, 2014 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-24742867

RESUMEN

TERT promoter mutations are identified in many malignancies including bladder cancer (BC) and upper tract urothelial carcinoma (UTUC). In contrast, no mutations were found in renal cell carcinoma (RCC) as reported in a recent study. Because the mutant TERT promoter in urine DNA was recently tested as a marker for BC, it is important to ascertain whether these mutations are truly absent in RCCs. Here we determined TERT promoter mutations in 109 patients with RCC and 14 patients with UTUC. The mutations were found in 9/96 (9.3%) clear cell RCC (ccRCC) tumors and 1/8 (13%) chromophobe RCC tumors. Among ccRCC patients, the mutation was correlated with the advanced stages and metastasis, and higher TERT expression. Among UTUCs, the mutation was detected in tumors from 3/5 (60%) patients with renal pelvic cancer and 1/9 (11%) patients with ureter cancer. The mutation was also detected in 1 of 4 urine samples from patients with mutation+ UTUC. Collectively, TERT promoter mutations do occur in RCCs and are associated with aggressive disease. The mutation is more frequent in renal pelvic cancer. Thus, the mutant TERT promoter found in urine may come from not only BC, but also RCC or UTUC.


Asunto(s)
Biomarcadores de Tumor/genética , Carcinoma de Células Renales/genética , ADN de Neoplasias/análisis , Neoplasias Renales/genética , Mutación , Regiones Promotoras Genéticas/genética , Telomerasa/genética , Neoplasias Ureterales/genética , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Renales/secundario , Carcinoma de Células Renales/orina , Análisis Mutacional de ADN , ADN de Neoplasias/orina , Femenino , Humanos , Neoplasias Renales/patología , Neoplasias Renales/orina , Pelvis Renal , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Ureterales/orina
17.
Biomed Rep ; 2(1): 105-111, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24649079

RESUMEN

Epidemiological studies have been conducted to evaluate genetic variations of murine double minute 2 (MDM2) SNP309 associated with the risk of gastric cancer (GC), although evidence remains conflicting. To gain a better understanding of this relationship, a meta-analysis was performed. Several electronic databases were searched up to February 2013, in order to identify relevant case-control studies. Seven published case-control studies with 2,199 cases and 3,201 controls were included. In the overall analysis, significant associations between the MDM2 SNP309 variant and GC risk were found for G vs. T alleles (OR=1.35; 95% CI, 1.24-1.47), GG vs. TT (OR=1.88; 95% CI, 1.59-2.24), recessive model (OR=1.71; 95% CI, 1.49-1.96). Furthermore, stratified by cancer site, significant associations were observed in gastric cardia cancer for all the models, although no significant association was found in any of the models among non-gastric cardia cancer, with the exception of the recessive model. In the subgroup analysis by source of control, MDM2 SNP309 was associated with increased GC risk for the hospital-based case-control (HCC) study for the GG vs. TT, recessive model and for the population-based case-control (PCC) study for the GG vs. TT, recessive model. Following stratification by gender and infection status of Helicobacter pylori (HP) for the recessive model, a significant association was found only in the HP-positive infected individuals. However, no statistically significant association was observed in males, females or the HP-negative infected individuals. In summary, the association between MDM2 SNP309 and GC risk was statistically significant, particularly in gastric cardia cancer for the HP-positive population group.

18.
J Natl Cancer Inst ; 105(22): 1719-28, 2013 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-24174655

RESUMEN

BACKGROUND: Androgen receptor (AR) is critical for prostate tumorigenesis and is frequently overexpressed during prostate cancer (PC) progression. However, few studies have addressed the epigenetic regulation of AR expression. METHODS: We analyzed SMYD3 expression in human PC with Western blot and immunohistochemistry. SMYD3 expression was knocked down using short hairpin RNA (shRNA) or small interfering RNA (siRNA). Cell proliferation, colony formation, and apoptosis analyses and xenograft transplantation were performed to evaluate the impact of SMYD3 depletion on PC cells. AR expression and promoter activity were determined using real-time quantitative polymerase chain reaction, western blot, and luciferase reporter assay. AR promoter association with Sp1, SMYD3, and histone modifications was assessed by chromatin immunoprecipitation. Differences in AR mRNA abundance and promoter activity were analyzed using Wilcoxon signed-rank tests, SMYD3 expression was analyzed using with Mann-Whitney U tests for unpaired samples, and tumor weight was analyzed with Student t test. All statistical tests were two-sided. RESULTS: The upregulation of SMYD3 protein expression was observed in seven of eight prostate tumor specimens, compared with matched normal tissues. Immunohistochemical analysis showed a strong SMYD3 staining in the nuclei of PC tissues in eight of 25 (32%) cases and in the cytoplasm in 23 out of 25 (92%) cases, whereas benign prostate tissue exhibited weak immunostaining. Depletion of SMYD3 by siRNA or shRNA inhibited PC cell proliferation (72 hours relative to 24 hours: control shRNA vs SMYD3 shRNA 1: mean fold change = 2.76 vs 1.68; difference = 1.08; 95% confidence interval = 0.78 to 1.38, P < .001), colony formation, cell migration, invasion, and xenograft tumor formation. Two functional SMYD3-binding motifs were identified in the AR promoter region. CONCLUSIONS: SMYD3 promotes prostate tumorigenesis and mediates epigenetic upregulation of AR expression.


Asunto(s)
N-Metiltransferasa de Histona-Lisina/genética , Neoplasias de la Próstata Resistentes a la Castración/genética , Neoplasias de la Próstata Resistentes a la Castración/patología , Receptores Androgénicos/genética , Transcripción Genética , Carcinogénesis , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Inmunoprecipitación de Cromatina , Epigénesis Genética , Regulación Neoplásica de la Expresión Génica , Humanos , Immunoblotting , Inmunohistoquímica , Masculino , Invasividad Neoplásica , Regiones Promotoras Genéticas , Neoplasias de la Próstata Resistentes a la Castración/metabolismo , ARN Interferente Pequeño/farmacología , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptores Androgénicos/metabolismo , Sincalida/metabolismo , Transfección , Regulación hacia Arriba , Ensayos Antitumor por Modelo de Xenoinjerto
19.
Oncol Lett ; 6(5): 1447-1452, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24179539

RESUMEN

Glioblastoma is the most malignant and common intrinsic brain tumor, but the molecular mechanism of glioma pathophysiology is poorly understood. Recent data have shown that microRNAs regulate the expression of several genes associated with human cancer. In the present study, the function of miR-34c in glioma cells was analyzed. It was demonstrated that miR-34c-3p and miR-34c-5p were downregulated in gliomas, by performing qPCR on tumor tissues from glioma patients and glioma cell lines, compared with normal brain tissues and a normal glial cell line. Furthermore, the miR-34c expression was found to be inversely correlated with glioma WHO grades. Overexpression of miR-34c-3p inhibited U251 and U87 cell proliferation; however, miR-34c-5p only had an effect on U251 cells. Transfection with miR-34c-3p or miR-34c-5p in U251 cells and with miR-34c-3p in U87 cells produced S-phase arrest with G0/G1 reduction and induced cell apoptosis, but no significant changes were observed with miR-34c-5p transfection in U87 cells, normal or negative control groups. However, significant inhibition of glioma cell invasion was observed following transfection with miR-34c-3p and miR-34c-5p. Moreover, it was identified that miR-34c-3p overexpression reduced the expression of Notch pathway members, but miR-34c-5p overexpression did not. Therefore, these results suggest differential tumor suppressor roles for miR-34c-3p and miR-34c-5p and provide new insights into the role of miR-34c in glioma, which includes tumor-suppressing effects on proliferation, apoptosis and invasiveness.

20.
Guang Pu Xue Yu Guang Pu Fen Xi ; 33(4): 872-6, 2013 Apr.
Artículo en Chino | MEDLINE | ID: mdl-23841388

RESUMEN

Silica sol was prepared by acid catalyzed sol-gel process using tetraethylorthosilicate (TEOS) as precursor and dimethyldietoxysilane (DDS) as pore-forming agent. A novel kind of monolayer microporous silica anti-reflective (AR) coating was obtained on K9 glass substrate by dip-coating technique and then heat treated at 500 degrees C. The effects of different DDS/TEOS molar ratios on refractive index, transmittance and hardness were investigated. A positive correlation was found between the transmittance and the DDS/TEOS molar ratio due to the increasing porosity. The maximum transmittance can reach 99.7% with the molar ratio of DDS/TEOS rising to 1 : 1. Meanwhile, the refractive index was found quite close to the ideal value 1.22. Nevertheless, higher molar ratio will lead to a bad film-forming property. On the other hand, the hardness of the coatings decreased with the DDS increasing but still remained more than 2 h when the transmittance reached highest. Besides, these coatings exhibit a well abrasion-resistance and excellent adhesivity. The maximum transmittance was only dropped by 0.071% and 0.112% after abrasion for 500 and 1 000 times respectively. Accelerated corrosion tests indicated that the transmittance of traditional coatings rapidly fell down to the substrate level (-92%) after immersion for 5 min, while the transmittance of our novel coating almost linearly decreased and was kept 93.2% after 56 min. In other words, the environment-resistance of our novel silica AR coating is ten times higher than that of traditional ones. The promotions of the coating performances benefit from its micropore structure (-0. 4 nm) with which water molecule can be effectively prevented. With its high transmittance, good mechanical properties and high environment-resistance, this kind of novel coating has a potential application in the field of solar glass modification to improve its anti-reflective properties.

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