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Osteosarcoma is a malignant bone tumor with extremely high invasion, metastasis and mortality. The prognosis of patients with osteosarcoma remains poor. The ErbB receptor family was found to be overexpressed in human cancers and associated with poor prognosis. However, the role of ErbB receptor family in osteosarcoma has not been fully understood. The present study aimed to investigate the clinicopathological and prognostic significances of ErbB receptors in primary osteosarcoma. Western blot (WB), reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and fluorescence in situ hybridization (FISH) were used to detect the protein and gene expression of ErbB receptors in 60 primary osteosarcoma specimens and 30 non-neoplastic bone tissues. WB and RT-qPCR analyses showed that the protein and mRNA expression levels of EGFR, ErbB3 and ErbB4 in osteosarcoma specimens were significantly higher than those in non-neoplastic bone tissues. Seventeen (28.33%), 15 (25.00%) and 15 (25.00%) osteosarcoma specimens presented with amplification of EGFR, ErbB3 and ErbB4 gene, respectively, which were significantly higher compared with non-neoplastic bone tissues. The amplification of ErbB3 and ErbB4 in osteosarcoma was associated with advanced surgical stage. The amplification of EGFR, ErbB3, ErbB4 and the co-amplification of EGFR-ErbB3, EGFR-ErbB4, ErbB3-ErbB4 was linked with poor response to chemotherapy and distant metastasis. The amplification of EGFR, ErbB3 and ErbB4, as well as their co-amplification demonstrated independent prognostic values for reduced survival time of osteosarcoma patients and may serve as potential therapeutic targets for osteosarcoma patients in the future.
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Receptores ErbB/genética , Amplificación de Genes , Osteosarcoma/genética , Osteosarcoma/patología , Adolescente , Adulto , Huesos/metabolismo , Huesos/patología , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , ARN Mensajero/genética , ARN Mensajero/metabolismo , Resultado del Tratamiento , Adulto JovenRESUMEN
Decreasing oocyte competence with maternal aging is a major factor in mammalian infertility. One of the factors contributing to this infertility is changes to chromatin modifications, such as histone acetylation in old MII stage oocytes. Recent studies indicate that changes in histone acetylation at MII arise at the germinal vesicle (GV) stage. We hypothesised that histone methylation could also change in old GV oocytes. To test this hypothesis, we examined mono-, di- and trimethylation of histone H3 lysine 4 (H3K4 me1, me2 and me3, respectively) in young and older oocytes from 6-8- and 42-44-week-old mice, respectively. We found that H3K4 me2 and me3 decreased in older compared with young GV oocytes (100% vs. 81% and 100% vs. 87%, respectively; P<0.05). H3K4 me2 later increased in older MII oocytes (21% vs. 56%; P<0.05). We also examined the expression of genes encoding the H3K4 demethylases lysine (K)-specific demethylase 1A (Kdm1a) and retinol binding protein 2 (Rbp2). Expression of Kdm1a increased at both the mRNA and protein levels in older GV oocytes, but decreased in older MII oocytes (P<0.05), and was negatively correlated with H3K4 me2 levels. Conversely, expression of Rbp2 mRNA and protein decreased in older GV oocytes (P<0.05), and this was not correlated with H3K4 me3 levels. Finally, we showed that inhibition of Kdm1a of older oocytes at the GV stage restored levels of H3K4 me2 at the MII stage to those seen in 'young' oocytes (41% vs. 38%; P>0.05). These results suggest that changes in expression of H3K4 me2 and Kdm1a in older GV oocytes may represent a molecular mechanism underlying human infertility caused by aging.
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Envejecimiento/fisiología , Núcleo Celular/metabolismo , Metilación de ADN/fisiología , Histonas/metabolismo , Infertilidad Femenina/etiología , Oocitos/metabolismo , Animales , Cartilla de ADN/genética , Femenino , Histona Demetilasas/metabolismo , Inmunohistoquímica , Técnicas de Maduración In Vitro de los Oocitos/métodos , Ratones , Microscopía Fluorescente , Reacción en Cadena en Tiempo Real de la Polimerasa , Proteínas Celulares de Unión al Retinol/metabolismo , TranilciprominaRESUMEN
BACKGROUND: To investigate the effect of raltitrexed + X-ray irradiation on esophageal cancer ECA109 cells and analyze the potential action mechanism. METHODS: The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to analyze the inhibitory effect of raltitrexed on cell proliferation. The effect of raltitrexed on radiosensitivity was studied through a clone-forming experiment. The scratch assay and invasion test were performed to understand the cell migration and invasion abilities. The apoptosis rate change was measured using a flow cytometer, and Western Blotting was used to determine the expression of B cell lymphoma-2 (Bcl-2) and Bcl2-associated X protein (Bax) in each group. RESULTS: Raltitrexed significantly inhibited ECA109 proliferation in a time-dose-dependent manner; there were significant differences among different concentrations and times of action. The results of the clone-forming experiment showed a sensitization enhancement ratio of 1.65, and this demonstrated a radiosensitization effect. After the combination of raltitrexed with X-ray, the cell migration distance was shortened, and the number of cells penetrating the membrane was reduced. CONCLUSION: Raltitrexed can inhibit the growth of esophageal cancer ECA109 cells and has a radiosensitization effect.
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Apoptosis , Proliferación Celular , Neoplasias Esofágicas , Quinazolinas , Humanos , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/metabolismo , Quinazolinas/farmacología , Proliferación Celular/efectos de los fármacos , Apoptosis/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Tiofenos/farmacología , Tioxantenos/farmacología , Tioxantenos/química , Tolerancia a Radiación/efectos de los fármacos , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Células Tumorales Cultivadas , Movimiento Celular/efectos de los fármacosRESUMEN
Introduction: Brain metastases (BM) from lung cancer are heterogeneous, and accurate prognosis is required for effective treatment strategies. This study aimed to identify prognostic factors and develop a prognostic system exclusively for epidermal growth factor receptor (EGFR)-mutated lung cancer BM. Methods: In total, 173 patients with EGFR-mutated lung cancer from two hospitals who developed BM and received tyrosine kinase inhibitor (TKI) and brain radiation therapy (RT) were included. Univariate and multivariate analyses were performed to identify significant EGFR-mutated BM prognostic factors to construct a new EGFR recursive partitioning analysis (RPA) prognostic index. The predictive discrimination of five prognostic scoring systems including RPA, diagnosis-specific prognostic factors indexes (DS-GPA), basic score for brain metastases (BS-BM), lung cancer using molecular markers (lung-mol GPA) and EGFR-RPA were analyzed using log-rank test, concordance index (C-index), and receiver operating characteristic curve (ROC). The potential predictive factors in the multivariable analysis to construct a prognostic index included Karnofsky performance status, BM at initial lung cancer diagnosis, BM progression after TKI, EGFR mutation type, uncontrolled primary tumors, and number of BM. Results and discussion: In the log-rank test, indices of RPA, DS-GPA, lung-mol GPA, BS-BM, and EGFR-RPA were all significant predictors of overall survival (OS) (p ≤ 0.05). The C-indices of each prognostic score were 0.603, 0.569, 0.613, 0.595, and 0.671, respectively; The area under the curve (AUC) values predicting 1-year OS were 0.565 (p=0.215), 0.572 (p=0.174), 0.641 (p=0.007), 0.585 (p=0.106), and 0.781 (p=0.000), respectively. Furthermore, EGFR-RPA performed better in terms of calibration than other prognostic indices.BM progression after TKI and EGFR mutation type were specific prognostic factors for EGFR-mutated lung cancer BM. EGFR-RPA was more precise than other models, and useful for personal treatment.
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PURPOSE: Endoscopic submucosal dissection (ESD) is a widely performed procedure for esophageal carcinoma when the depth of invasion reaches the epithelium and lamina propria. However, ESD for esophageal carcinoma with depth of invasion exceeding the muscularis mucosa is controversial. This study aimed to evaluate the long-term outcomes of ESD for T1N0M0 (tumor invading the mucosa and submucosa [T1], no regional lymph node metastasis [N0], no distant metastasis [M0]) esophageal cancer. PATIENTS AND METHODS: Esophageal cancer was evaluated via pathology and computed tomography (CT) in consecutive patients with negative margin and without additional therapy. A total of 84 patients were included. The mean follow-up time was 42 (range, 9-99) months. RESULTS: No recurrence and metastasis were detected in the M1 and M2 group. The 5-year locoregional recurrence rate and distant metastasis rate were 4.2% and 5.6% for the M3 group and were 0% and 1.4% for the SM group, respectively. The 3- and 5-year overall survival were 94.4% (M1+M2 group, 95.0%; M3 group, 95.0%; SM group, 92.9%) and 80.9% (M1+M2 group, 95.0%; M3 group, 95.0%; SM group, 92.9%). Meanwhile, the 3- and 5-year disease-specific survival rates were 100% (M1+M2 group, 100%; M3 group, 100%; SM group, 100%) and 90.8% (M1+M2 group, 100%; M3 group, 90.0%; SM group, 85.7%). The major complications were postoperative strictures, most of which were grade 1-2. In total, two (4.8%) and one (1.2%) patient developed grade 3 and 5 late esophageal strictures, respectively. CONCLUSION: ESD complete resection yields low recurrence and metastasis rates in early esophageal cancer (T1N0M0). Thus, additional treatment is not necessary, and a watch and wait strategy may be reasonable.
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The death-associated protein kinase 1 (DAPK1) gene is a candidate tumor suppressor (TSG) and the abnormal methylation of DAPK1 gene has been found in many carcinomas. The epigenetic changes of TSGs are now recognized as a mechanism contributing to the development of chronic myeloid leukemia (CML). To clarify the role of DAPK1 in CML, we examined the methylation status of DAPK1 in 49 patients with CML using methylation-specific polymerase chain reaction. The aberrant methylation of the DAPK1 gene was found in 25 of 49 (51.0%) CML cases, not in all controls. No correlation was found between DAPK1 gene methylation and the age, hematologic parameters, chromosomal abnormalities, the types and levels of bcr/abl transcripts of CML patients. However, correlation could be observed between the sex and the status of DAPK1 methylation in CML patients (R = 0.374, P = 0.008). Furthermore, there was a significant correlation between DAPK1 methylation and the stages of CML (R = 0.354, P = 0.013). The CML patients in accelerated phase (AP) and blast crisis (BC) had higher frequency of DAPK1 methylation than those in chronic phase (CP) (75.0% vs. 34.5%) (chi(2) = 7.776, P = 0.005). In one patient, the status of DAPK1 methylation became positive on the transition from CP to AP and BC. These results suggested that DAPK1 promoter methylation might play a significant role in the progression of CML.
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Proteínas Reguladoras de la Apoptosis/genética , Proteínas Quinasas Dependientes de Calcio-Calmodulina/genética , Islas de CpG , Metilación de ADN , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Adulto , Anciano , Secuencia de Bases , Cartilla de ADN , Proteínas Quinasas Asociadas a Muerte Celular , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Regiones Promotoras Genéticas , Homología de Secuencia de Ácido NucleicoRESUMEN
PRI (Photochemical reflectance index) has provided a fast and reliable method for estimating photosynthetic light use efficiency across species. Increasing efforts have been paid to explore the effects of such disturbances as water content and CO2 concentration on the relationship between PRI and LUE. In the present paper, five types of wheat with different nitrogen and kalium fertilization were selected to study the influence of varied fertilization levels on the relationship between PRI and LUE. The results proved that leaf chlorophyll contents as well as canopy PRI increased with the increase in nitrogen and kalium fertilization. For all the nitrogen and kalium fertilization of wheat, the regression coefficients R2 are 0.710 4 and 0.853 4 respectively. When considering different levels of fertilization, the regression coefficients R2 are 0.602 0, 0.640 4 and 0.801 4 for three types of nitrogen fertilization, and 0.379 1, 0.640 4 and 0.676 9 for kalium fertilization. Therefore, PRI not only can be a reliable indicator of LUE but also can reflect the fertilization situation of wheat with different precisions of LUE assessment which can provide important reference for management and precision agriculture.
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Photochemical reflectance index (PRI) defined as a normalized difference index using two narrow reflectance bands at 531 and 570 nm that are closely related to xanthophyll cycle pigment content has been successfully used to estimate leaf photosynthetic light use efficiency (LUE) across species which vary in water content and nitrogen concentration. Previous research demonstrated that a consistent relationship could be established between PRI and LUE calculated from gas exchange measurements at the leaf, small canopy, and full forest or crop canopy scales. However, a number of problems, such as the saturation of PRI when LUE exceeds 0.03 mol CO2 mol(-1) PPED (photosynthetic photon flux density) and disjunctive relationships of PRI and LUE in seasonal changes, still existed and need to be handled in order to evaluate LUE more accurately. A sensitivity study of a revised PRI with four leaf parameters was performed based on PROSPECT model in the present article to study the effects of different biochemical concentrations on leaf SR-PRI (simple ratio PRI). Sensitivity study proved that leaf SR-PRI is more sensitive to leaf mesophyll structure parameter (N) and chlorophyll a + b content (c(ab)) than parameters of dry matter content (c(m)) and equivalent water thickness (c(w)), indicating that leaf mesophyll structure parameter (N) and chlorophyll a + b content (c(ab)) should be especially considered when acquiring leaf SR-PRI. And changes in the two parameters would cause large variation in SR-PRI which would reduce the precision for estimating light use efficiency. Validation study of SR-PRI was carried out in the analysis and the results proved that SR-PRI can also be a feasible index of estimating LUE for four species of plants with correlation coefficients better than that of PRI and LUE. The advantage of SR-PRI compared to PRI is its much clearer physical meaning and its sensitivity to the changes in reflectance at 531 nm which serves as a core parameter to evaluate light use efficiency.
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OBJECTIVE: To investigate the mortality from main causes of death in 6 tungsten miners and explore the effects of cumulative dust exposure on standardized mortality ratios (SMRs) from main causes. METHODS: A cohort of 18027 workers registered in the employment record from 6 tungsten mines located in Hunan and Jiangxi province and working for at least 1 year was identified for this study. SMRs were calculated based on Chinese national mortality. Trend analysis was used to analyze the effect of cumulative dust exposure on SMRs of main causes of death. RESULTS: The cohort was followed up from 1972 to 2003 with an accumulative of 470 722.21 person-years. A total of 6135 workers died, and the mortality was 13.03 per thousand. Cardiovascular disease, respiratory disease, malignant neoplasm and pulmonary tuberculosis accounted for 79.32% of all death. The mortalities of all-causes, pneumoconiosis, pulmonary tuberculosis, nasopharyngeal carcinoma, infectious disease, respiratory disease, cardiovascular disease and liver cancer were found to be significantly higher than the national average level. Positive dose-response relationship between SMRs and cumulative dust exposure was observed in all-causes, pneumoconiosis, pulmonary tuberculosis, respiratory disease, cardiovascular disease (P < 0.01). CONCLUSION: The mortality from main causes of death for the dust-exposed workers are higher than that for non dust-exposed workers. Positive dose-response relationships are observed between cumulative dust exposure and SMRs from all-causes, respiratory disease (including silicosis), pulmonary tuberculosis and cardiovascular disease.
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Causas de Muerte , Minería , Exposición Profesional/efectos adversos , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Polvo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Silicosis/mortalidad , TungstenoRESUMEN
BACKGROUND: Kidney cancer is one of the most common cancers in the USA causing 14,400 deaths per year. The phosphatase and tensin homolog (PTEN) has been extensively documented as a tumor suppresser gene in cancer. However, there is unclear evidence for its clinicopathological and prognostic role in kidney cancer. METHODS: A systematic review of literature assessing PTEN expression and clinical outcome in patients with kidney cancer. Web of Science, PubMed, Embase, and Chinese databases were searched for collecting for the eligible studies providing sufficient information. Pooled odds ratios (ORs) and hazard ratios (HRs) were respectively used to evaluate the association between PTEN levels and the clinicopathological features and clinical outcomes. RESULTS: A total of 35 studies enrolling 4532 patients were finally included in this study. For the survival outcome, the result suggested that shorter overall survival (OS) was correlated with low PTEN expression (HRâ¯=â¯0.57, 95% CIs: 0.45-0.74, Pâ¯<â¯0.0001). The meta-analysis indicated a significantly increased risk of tumorigenesis in the PTEN low-level group relative to the control group (ORâ¯=â¯0.098, 95% CIs: 0.067-0.143, Pâ¯<â¯0.001). Moreover, the results displayed the positive correlation between poorer differentiation (ORâ¯=â¯0.234, 95% CIs: 0.133-0.410, Pâ¯<â¯0.001), distant metastasis (ORâ¯=â¯0.179, 95% CIs: 0.092-0.350, Pâ¯=â¯0.001), lymph node metastasis (ORâ¯=â¯0.252, 95% CIs: 0.113-0.563, Pâ¯<â¯0.001), advanced clinical stages (ORâ¯=â¯0.233, 95% CI: 0.133, 0.406, Pâ¯<â¯0.001) and low PTEN expression. Finally, there was no obvious publication bias found in the meta-analysis. CONCLUSIONS: Decreased PTEN was associated with poorer survival outcomes of patients with kidney cancer and PTEN acts as a tumor suppressor in tumorigeneses and progression in kidney cancer.
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Neoplasias Renales/genética , Fosfohidrolasa PTEN/genética , Humanos , Neoplasias Renales/patología , Tasa de SupervivenciaRESUMEN
BACKGROUND/AIM: Radiation pneumonia is a main side-effect that has limited the clinical usage of radiotherapy in locally advanced esophageal carcinoma. T helper cells 17 (Th 17) and T regulatory cells (Tregs) play an important role in inflammatory diseases. The balance between Treg and Th17 cells is a key factor in the progression of many inflammatory and autoimmune diseases. Whether Tregs and Th17 cells are predictive factors of radiation pneumonia has not yet been reported. In this study, we investigated the relationships of Treg/Th17 cells and radiation pneumonia in patients with locally advanced esophageal cancer who received radiotherapy. PATIENTS AND METHODS: One hundred and forty-eight patients with locally advanced esophageal cancer who received radical and palliative radiotherapy were enrolled. The levels of Th17 and Treg cells in the blood of patients were detected using flow cytometry at the time point of pre-radiotherapy, 1st, 2nd, 3rd, 4th, 5th and 6th week from the start of radiation and 4 weeks after completion of radiotherapy. Radiation pneumonia was evaluated according to Radiation Therapy Oncology Group's acute radiation pneumonia standards, with the endpoint being grade 2 or above radiation pneumonia. RESULTS: There were 24 cases of radiation pneumonia in 148 cases of locally advanced esophageal cancer patients who underwent radiotherapy. Th17 cells increased and, in contrast, Treg cells decreased in the radiation pneumonia group. The change in the ratio of Th17/Treg was more pronounced and the difference was statistically significant from the 5th week after irradiation compared to patients with no radiation pneumonia (p<0.05). There was no significant difference in dosimetric parameters, including V5, V20, V30 and mean lung dose (MLD) and clinical factors, such as gender, age, smoking history, history of surgery and chemotherapy. CONCLUSION: The ratio of Th17/Treg cells may be an effective predictive factor of radiation pneumonia.
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Neoplasias Esofágicas/complicaciones , Neoplasias Esofágicas/inmunología , Neumonitis por Radiación/etiología , Linfocitos T Reguladores/inmunología , Células Th17/inmunología , Adulto , Anciano , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/radioterapia , Femenino , Estudios de Seguimiento , Humanos , Inmunofenotipificación , Incidencia , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Fenotipo , Neumonitis por Radiación/diagnóstico , Neumonitis por Radiación/epidemiología , Factores de Riesgo , Linfocitos T Reguladores/metabolismo , Células Th17/metabolismoRESUMEN
Recently, we have demonstrated that PRSS1 mutations cause ectopic trypsinogen activation and thereby result in type 1 autoimmune pancreatitis (AIP). However, the molecules involved in inducing obliterative vasculitis and perineural inflammation in the pancreas are not well-described. The present study applied whole-exome sequencing (WES) to determine the underlying etiology and revealed novel missense splice region variants, CALCB c.88T>C (p.Ser30Pro) and IR [1]-mutants, in 2 of the 3 families and 2 of 26 unrelated patients with type 1 AIP. In vitro, both of the mutants displayed decreased ßCGRP, ERK1/2 phosphorylation, and co-localized with endoplasmic reticulum and Golgi apparatus. The novel pathogenic variant identified in this case should contribute to our understanding of the expanding spectrum of AIP.
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Enfermedades Autoinmunes/genética , Enfermedades Autoinmunes/patología , Péptido Relacionado con Gen de Calcitonina/genética , Mutación/genética , Pancreatitis/genética , Pancreatitis/patología , Células Plasmáticas/patología , Línea Celular , Retículo Endoplásmico/genética , Femenino , Aparato de Golgi/genética , Células HEK293 , Humanos , Inflamación/genética , Inflamación/patología , Sistema de Señalización de MAP Quinasas/genética , Masculino , Páncreas/patología , Fosforilación/genética , Tripsina/genéticaRESUMEN
BACKGROUND: Nonsurgical pathologic diagnosis of malignant bile duct stricture with a high sensitivity and specificity is desirable for therapeutic scheme. Percutaneous transhepatic endobiliary brush cytology in detecting obstructive jaundice is evaluated. METHODS: Fifty-eight consecutive patients with obstructive jaundice underwent percutaneous transhepatic cholangiodrainage (PTCD). During the process, a brush was inserted into the bile duct through the preexisted percutaneous transhepatic 8-F sheath, then exfoliated cells were collected from the bile duct stenosis and sent for cytologic diagnosis. The suspicious results were considered of negative diagnosis. All patients had relevant clinical data and follow-up results (15 months to 3 years). Statistical analysis was performed with the chi-square test and Fisher's exact test of probabilities, and a P value=0.05 was considered significantly different. RESULTS: Of all patients, 42 were diagnosed as having malignant stenosis according to brush cytology. Atypical hyperplasia was found in 9 patients and was suspicious of cholangiocarcinoma. Seven patients were found to have benign strictures. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of brush cytology were 75%(42/56), 100%(2/2), 100%(42/42), 12.5%(2/16), and 75.9%(44/58), respectively. No complications were related to the procedures. In all patients with malignant stenosis, the sensitivity of brushing in diagnosis of cholangiocarcinoma was greater than that in those with non-cholangiocarcinoma (P<0.05). The site of stenosis did not influence the sensitivity and technical success (P>0.05). CONCLUSION: The results of this study indicate that cytological brushing of biliary stricture during PTCD is a useful method to establish a diagnosis of malignant biliary stenosis with a high sensitivity, but the negative predictive value is not satisfied.
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Neoplasias de los Conductos Biliares/patología , Colangiocarcinoma/patología , Colangiopancreatografia Retrógrada Endoscópica/instrumentación , Ictericia Obstructiva/patología , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de los Conductos Biliares/diagnóstico , Neoplasias de los Conductos Biliares/cirugía , Biopsia con Aguja , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/cirugía , Colangiopancreatografia Retrógrada Endoscópica/métodos , Estudios de Cohortes , Citodiagnóstico/métodos , Drenaje/métodos , Diseño de Equipo , Seguridad de Equipos , Femenino , Humanos , Inmunohistoquímica , Ictericia Obstructiva/diagnóstico , Ictericia Obstructiva/cirugía , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Valor Predictivo de las Pruebas , Probabilidad , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
Vitronectin (Vn), a multifunctional adhesive protein, is found in association with tumor progression, angiogenesis and metastasis in a variety of (human) tumors. But no studies concerning its correlation to osteosarcoma prognosis were found. Hence, we aimed to investigate the prognostic value of Vitronectin (Vn) in osteosarcoma. Here, we studied the expression of VN in the tumor tissues from 67 patients with osteosarcoma and 20 patients with osteochondroma using immunohistochemistry and estimated the effects of VN expression in osteosarcoma on progression-free survival (PFS) and overall survival (OS) using the Kaplan-Meier curve and COX proportional hazards regression model. Increased expression of VN in osteosarcoma tissue compared to no VN expression in osteochondroma tissue was shown in immunohistochemical assay. No associations were observed between VN expression and osteosarcoma patients' gender (P = 0.675), age (P = 0.813), tumor size (P = 0.436), histologic subtype (P = 0.0.543) or tumor location (P = 0.456). Univariate survival analysis demonstrated significant correlations of high VN expression with shorter PFS (P = 0.002) and OS (P = 0.001); multivariate survival analysis revealed high VN expression as a significant independent prognostic indicator for shorter PFS (HR 2.788, P = 0.003) and OS (HR2.817, P = 0.003). In conclusion, the high expression of VN in tumor cells independently indicated poor clinical prognosis in patients with osteosarcoma, other than large tumor size and non-neoadjuvant chemoradiotherapy, suggesting that VN may serve as a potential therapeutic target in osteosarcoma.
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Biomarcadores de Tumor/análisis , Neoplasias Óseas/química , Osteosarcoma/química , Vitronectina/análisis , Adolescente , Adulto , Anciano , Neoplasias Óseas/mortalidad , Neoplasias Óseas/patología , Neoplasias Óseas/terapia , Quimioradioterapia Adyuvante , Distribución de Chi-Cuadrado , Niño , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Terapia Neoadyuvante , Osteosarcoma/mortalidad , Osteosarcoma/patología , Osteosarcoma/terapia , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Carga Tumoral , Regulación hacia Arriba , Adulto JovenRESUMEN
OBJECTIVE: To evaluate the implementation and effectiveness of comprehensive control measures of schistosomiasis in Caidian District, Wuhan City. METHODS: The data of implementation of the schistosomiasis control measures in Caidian District was collected and analyzed statistically. RESULTS: The number of Oncomelania hupensis snail environments and snail area decreased from 213 sites and 223.47 hm2 in 2003 to 59 sites and 51.20 hm2 in 2013, with the decreasing rate of 72.30% and 77.09%, respectively. The infection rate of schistosomiasis of human decreased from 1.58% in 2006 to 0.24% in 2013, with the decreasing rate of 84.81%. The positive rate of stool tests of cattle was 2.19% in 2006 while it was 0 in 2013. CONCLUSION: The comprehensive control measures of schistosomiasis are effective.
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Enfermedades de los Bovinos/prevención & control , Control de Enfermedades Transmisibles/métodos , Esquistosomiasis/prevención & control , Esquistosomiasis/veterinaria , Caracoles/parasitología , Adolescente , Adulto , Anciano , Agricultura/instrumentación , Agricultura/métodos , Animales , Bovinos , Enfermedades de los Bovinos/epidemiología , Enfermedades de los Bovinos/parasitología , Niño , China/epidemiología , Control de Enfermedades Transmisibles/instrumentación , Reservorios de Enfermedades/parasitología , Heces/parasitología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Schistosoma/aislamiento & purificación , Schistosoma/fisiología , Esquistosomiasis/epidemiología , Esquistosomiasis/parasitología , Adulto JovenRESUMEN
The current study was performed to evaluate the mechanisms and therapeutic effects of overexpressing neuroglobin (Ngb) on spinal cord injury (SCI). Adeno-associated virus (AAV) was injected in the T12 section 7 days before SCI. Animals were randomly divided into four groups: a sham group, a vehicle group, an AAV-EGFP group and an AAV-Ngb group. Recovery of hind limb locomotor function was determined during the 3-week post operation period by the Basso, Beattie and Bresnahan locomotor rating scale. At 24 h after SCI and at the end of the study, the segments of spinal cord, centered with the lesion site were harvested for histopathological analysis. Immunofluorescence was performed using antibodies to recognize neuN in the lesion sections. At 24 h after SCI, the spinal cord tissue samples were removed to analyze tissue concentrations of superoxide dismutase (SOD) and malondialdehyde (MDA). Apoptotic cells were assessed using a terminal deoxynucleotidyl transferase, dUTP nick end labeling (TUNEL) kit. The expression of bcl-2, bax, cytochrome c, and cleaved caspase-3, were determined by Western blot assay and immunostaining analysis. The results showed that animals overexpressing Ngb had significantly greater recovery of locomotor function, less neuronal loss and fewer apoptotic cells. In addition, overexpressing Ngb significantly increased bcl-2 expression and SOD level, decreased bax expression, attenuated the release of cytochrome c from mitochondria to the cytosol fraction, and reduced the activity of caspase-3 and MDA level after SCI. These findings suggest, that overexpressing Ngb can significantly improve the recovery of locomotor function. This neuroprotective effect may be associated with the inhibition of neural apoptosis via the mitochondrial pathway.
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Terapia Genética , Globinas/genética , Globinas/metabolismo , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Neuronas/fisiología , Recuperación de la Función/fisiología , Traumatismos de la Médula Espinal/terapia , Médula Espinal/fisiopatología , Animales , Apoptosis/fisiología , Supervivencia Celular/fisiología , Dependovirus , Vectores Genéticos , Miembro Posterior , Masculino , Actividad Motora , Neuroglobina , Oxidación-Reducción , Distribución Aleatoria , Ratas Sprague-Dawley , Traumatismos de la Médula Espinal/fisiopatología , Vértebras TorácicasRESUMEN
OBJECTIVE: This study aims to investigate the potentially protective effect of neuroglobin (Ngb) gene-modified bone marrow mesenchymal stem cells (BMSCs) on traumatic spinal cord injury (SCI) in rabbits. METHODS: A lentiviral vector containing an Ngb gene was constructed and used to deliver Ngb to BMSCs. Ngb gene-modified BMSCs were then injected at the SCI sites 24 hours after SCI. The motor functions of the rabbits were evaluated by the Basso-Beattie-Bresnahan rating scale. Fluorescence microscopy, quantitative real-time PCRs, Western blots, malondialdehyde (MDA) tests, and terminal deoxynucleotidyltransferase-mediated UTP end labeling assays were also performed. RESULTS: Ngb expression in the Ngb-BMSC group increased significantly. A more significant functional improvement was observed in the Ngb-BMSC group compared with those in the other groups. Traumatic SCI seemingly led to an increase in MDA level and number of apoptotic cells, which can be prevented by Ngb-BMSC treatment. CONCLUSION: This study demonstrates that Ngb gene-modified BMSCs can strengthen the therapeutic benefits of BMSCs in reducing secondary damage and improving the neurological outcome after traumatic SCI. Therefore, the combined strategy of BMSC transplantation and Ngb gene therapy can be used to treat traumatic SCI.
Asunto(s)
Células de la Médula Ósea/citología , Técnicas de Transferencia de Gen , Globinas/genética , Trasplante de Células Madre Mesenquimatosas/métodos , Proteínas del Tejido Nervioso/genética , Traumatismos de la Médula Espinal/cirugía , Animales , Malondialdehído/metabolismo , Neuroglobina , Conejos , Traumatismos de la Médula Espinal/genética , Traumatismos de la Médula Espinal/metabolismo , Transgenes/genética , Regulación hacia ArribaRESUMEN
AIM: To elucidate high mobility group-box 3 (HMGB3) protein expression in gastric adenocarcinoma, its potential prognostic relevance, and possible mechanism of action. METHODS: Ninety-two patients with gastric adenocarcinomas surgically removed entered the study. HMGB3 expression was determined by immunohistochemistry through a tissue microarray procedure. The clinicopathologic characteristics of all patients were recorded, and regular follow-up was made for all patients. The inter-relationship of HMGB3 expression with histological and clinical factors was analyzed using nonparametric tests. Survival analysis was carried out by Kaplan-Meier (log-rank) and multivariate Cox (Forward LR) analyses between the group with overexpression of HMGB3 and the group with low or no HMGB3 expression to determine the prognosis value of HMGB3 expression on overall survival. Further, HMGB3 expression was knocked down by small hairpin RNAs (shRNAs) in the human gastric cancer cell line BGC823 to observe its influence on cell biological characteristics. The MTT method was utilized to detect gastric cancer cell proliferation changes, and cell cycle distribution was analyzed by flow cytometry. RESULTS: Among 92 patients with gastric adenocarcinomas surgically removed in this study, high HMGB3 protein expression was detected in the gastric adenocarcinoma tissues vs peritumoral tissues (P < 0.001). Further correlation analysis with patients' clinical and histology variables revealed that HMGB3 overexpression was obviously associated with extensive wall penetration (P = 0.005), a positive nodal status (P = 0.004), and advanced tumor-node-metastasis (TNM) stage (P = 0.001). But there was no correlation between HMGB3 overexpression and the age and gender of the patient, tumor localization or histologic grade. Statistical Kaplan-Meier survival analysis disclosed significant differences in overall survival between the HMGB3 overexpression group and the HMGB3 no or low expression group (P = 0.006). The expected overall survival time was 31.00 ± 3.773 mo (95%CI = 23.605-38.395) for patients with HMGB3 overexpression and 49.074 ± 3.648 mo (95%CI = 41.925-57.311) for patients with HMGB3 no and low-level expression. Additionally, older age (P = 0.040), extensive wall penetration (P = 0.008), positive lymph node metastasis (P = 0.005), and advanced TNM tumor stage (P = 0.007) showed negative correlation with overall survival. Multivariate Cox regression analysis indicated that HMGB3 overexpression was an independent variable with respect to age, gender, histologic grade, extent of wall penetration, lymph nodal metastasis, and TNM stage for patients with resectable gastric adenocarcinomas with poor prognosis (hazard ratio = 2.791, 95%CI = 1.233-6.319, P = 0.019). In the gene function study, after HMGB3 was knocked down in the gastric cell line BGC823 by shRNA, the cell proliferation rate was reduced at 24 h, 48 h and 72 h. Compared to BGC823 shRNA-negative control (NC) cells, the cell proliferation rate in cells that had HMGB3 shRNA transfected was significantly decreased (P < 0.01). Finally, cell cycle analysis by FACS showed that BGC823 cells that had HMGB3 knocked down were blocked in G1/G0 phase. The percentage of cells in G1/G0 phase in BGC823 cells with shRNA-NC and with shRNA-HMGB3 was 46.84% ± 1.7%, and 73.03% ± 3.51% respectively (P = 0.001), whereas G2/M cells percentage decreased from 26.51% ± 0.83% to 17.8% ± 2.26%. CONCLUSION: HMGB3 is likely to be a useful prognostic marker involved in gastric cancer disease onset and progression by regulating the cell cycle.