RESUMEN
ABSTRACT Introduction Study the relationship between the metabolic enzyme and the biological image, filtered by an adaptive filtering algorithm. Objective The research aims to In this study, human metabolic enzymes were evaluated by electrocardiogram and electromyogram images, and an adaptive filtering algorithm removed the noises in the images. Methods The electrocardiogram and electromyogram images at different periods were obtained, and the calculation method and application scope of the adaptive filtering algorithm were analysed. Results Adaptive filter was designed by the combination of adaptive filtering algorithm and dynamic information. Therefore, the artefact of the image was removed. Conclusions The adaptive filtering algorithm can effectively remove the noise or artefact in electrocardiogram and electromyogram signals. The optimal image information can be obtained. Level of evidence II; Therapeutic studies - investigation of treatment results.
RESUMO Introdução Estudar a relação entre a enzima metabólica e a imagem biológica filtrada por um algoritmo de filtragem adaptativa. Objetivo O objetivo da pesquisa, neste estudo, é avaliar enzimas metabólicas humanas por meio de imagens de eletrocardiograma e eletromiograma, sendo que um algoritmo de filtragem adaptativa eliminou o ruído nas imagens. Métodos Imagens de eletrocardiograma e eletromiograma foram obtidas em diferentes períodos e foram analisados o método de cálculo e o escopo de aplicação do algoritmo de filtragem adaptativa. Resultados a filtragem adaptativa foi projetada combinando um algoritmo de filtragem adaptativa e informações dinâmicas. Portanto, o artefato foi removido da imagem. Conclusões O algoritmo de filtragem adaptativa pode efetivamente eliminar ruído ou artefato em sinais de eletrocardiograma e eletromiograma. Informações de imagem ideais podem ser obtidas. Nível de evidência II; Estudos terapêuticos: investigação dos resultados do tratamento.
RESUMEN Introducción Estudiar la relación entre la enzima metabólica y la imagen biológica, filtrada por un algoritmo de filtrado adaptativo. Objetivo La investigación tiene como objetivo, en este estudio, evaluar las enzimas metabólicas humanas mediante imágenes de electrocardiograma y electromiograma, y un algoritmo de filtrado adaptativo eliminó los ruidos en las imágenes. Métodos Se obtuvieron las imágenes de electrocardiograma y electromiograma en diferentes períodos y se analizó el método de cálculo y alcance de aplicación del algoritmo de filtrado adaptativo. Resultados El filtrado adaptativo se diseñó mediante la combinación de un algoritmo de filtrado adaptativo e información dinámica. Por lo tanto, se eliminó el artefacto de la imagen. Conclusiones El algoritmo de filtrado adaptativo puede eliminar eficazmente el ruido o artefacto en las señales de electrocardiograma y electromiograma. Se puede obtener la información de imagen óptima. Nivel de evidencia II; Estudios terapéuticos: investigación de los resultados del tratamiento.
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Fatiga/enzimología , Fatiga/metabolismo , Músculos/metabolismo , Algoritmos , Electrocardiografía , Electromiografía , Modelos BiológicosRESUMEN
ABSTRACT Introduction High-intensity rehabilitation training will produce exercise fatigue. Objective A backpropagation (BP) network neural algorithm is proposed to predict sports fatigue based on electromyography (EMG) signal images. Methods The principal component analysis algorithm is used to reduce the dimension of EMG signal features. The knee joint angle is estimated by the regularized over-limit learning machine algorithm and the BP neural network algorithm. Results The RMSE value of the regularized over-limit learning machine algorithm is lower than that of the BP neural network algorithm. At the same time, the ρ value of the regularized over-limit learning machine algorithm is closer to 1, indicating its higher accuracy. Conclusions The model training time of the regularized over-limit learning machine algorithm has been greatly reduced, which improves efficiency. Level of evidence II; Therapeutic studies - investigation of treatment results.
RESUMO Introdução O treinamento de reabilitação de alta intensidade produzirá fadiga ao exercício. Objetivo Um algoritmo neural de backpropagation network (BP) é proposto para prever a fadiga esportiva com base em imagens de sinais de eletromiografia (EMG). Métodos O algoritmo de análise de componente principal é usado para reduzir a dimensão das características do sinal EMG. O ângulo da articulação do joelho é estimado usando o algoritmo de aprendizado de máquina de limite regularizado acima e o algoritmo de rede neural BP. Resultados o valor RMSE do algoritmo de aprendizado de máquina acima do limite regularizado é menor que o do algoritmo de rede neural BP. Ao mesmo tempo, o valor de ρ do algoritmo de aprendizado de máquina acima do limite regularizado está próximo de 1, indicando sua maior precisão. Conclusões O tempo de treinamento do modelo de algoritmo de aprendizado de máquina acima do limite regularizado foi bastante reduzido, o que melhora a eficiência. Nível de evidência II; Estudos terapêuticos: investigação dos resultados do tratamento.
RESUMEN Introducción El entrenamiento de rehabilitación de alta intensidad producirá fatiga por ejercicio. Objetivo Se propone un algoritmo neuronal de red de retropropagación (BP) para predecir la fatiga deportiva basándose en imágenes de señales de electromiografía (EMG). Métodos El algoritmo de análisis de componentes principales se utiliza para reducir la dimensión de las características de la señal EMG. El ángulo de la articulación de la rodilla se estima mediante el algoritmo de la máquina de aprendizaje por encima del límite regularizado y el algoritmo de red neuronal BP. Resultados el valor de RMSE del algoritmo de la máquina de aprendizaje por encima del límite regularizado es menor que el del algoritmo de red neuronal de BP. Al mismo tiempo, el valor ρ del algoritmo de la máquina de aprendizaje por encima del límite regularizado está más cerca de 1, lo que indica su mayor precisión. Conclusiones El tiempo de entrenamiento del modelo del algoritmo de la máquina de aprendizaje por encima del límite regularizado se ha reducido en gran medida, lo que mejora la eficiencia. Nivel de evidencia II; Estudios terapéuticos: investigación de los resultados del tratamiento.
Asunto(s)
Humanos , Análisis de Componente Principal , Fatiga , Entrenamiento de Intervalos de Alta Intensidad , Algoritmos , Procesamiento de Señales Asistido por Computador , Electromiografía , Articulación de la Rodilla/fisiologíaRESUMEN
BACKGROUND: The accessory ß1 subunits, regulating the pharmacological and biophysical properties of BK channels, always undergo post-translational modifications, especially glycosylation. To date, it remains elusive whether the glycosylation contributes to the regulation of BK channels by ß1 subunits. METHODS: Herein, we combined the electrophysiological approach with molecular mutations and biochemical manipulation to investigate the function roles of N-glycosylation in ß1 subunits. RESULTS: The results show that deglycosylation of ß1 subunits through double-site mutations (ß1 N80A/N142A or ß1 N80Q/N142Q) could significantly increase the inhibitory potency of iberiotoxin, a specific BK channel blocker. The deglycosylated channels also have a different sensitivity to martentoxin, another BK channel modulator with some remarkable effects as reported before. On the contrary to enhancing effects of martentoxin on glycosylated BK channels under the presence of cytoplasmic Ca2+, deglycosylated channels were not affected by the toxin. However, the deglycosylated channels were surprisingly inhibited by martentoxin under the absence of cytoplasmic Ca2+, while the glycosylated channels were not inhibited under this same condition. In addition, wild type BK (α+ß1) channels treated with PNGase F also showed the same trend of pharmacological results to the mutants. Similar to this modulation of glycosylation on BK channel pharmacology, the deglycosylated forms of the channels were activated at a faster speed than the glycosylated ones. However, the V1/2 and slope were not changed by the glycosylation. CONCLUSION: The present study reveals that glycosylation is an indispensable determinant of the modulation of ß1-subunit on BK channel pharmacology and its activation. The loss of glycosylation of ß1 subunits could lead to the dysfunction of BK channel, resulting in a pathological state.
RESUMEN
The Wukongopteridae is a transitional clade between the long- and short-tailed pterosaur groups, and at least ten specimens have been studied without a determined juvenile specimen. Here, we described a small-sized Kunpengopterus sinensis, less than half the size of the holotype, which is the smallest specimen in wukongopterids. Based on unossified small elements, unfused cranial and postcranial elements, and grooves on the bone surface, this specimen is thought to be at least an early juvenile or even a late hatchling. By comparing the juvenile and subadult specimens of K. sinensis, we have found that the mid region of the upper and lower jaws had a higher growth rate than the anterior part, and that the growth rates were similar in most postcranial elements except for a higher rate in the caudal vertebrae. We revised the previous diagnosis of K. sinensis and specified that two characteristics, nasoantorbital fenestra approximately 40% of the skull length and a thin and relatively short maxillary process of the jugal, should be diagnostic in subadult or adult specimens. We have also found that pedal features are stable during ontogeny and can be diagnostic in juvenile, subadult or adult specimens in K. sinensis.
Asunto(s)
Dinosaurios , Animales , China , Dinosaurios/anatomía & histología , Fósiles , Mandíbula , Cráneo/anatomía & histologíaRESUMEN
The accessory ß1 subunits, regulating the pharmacological and biophysical properties of BK channels, always undergo post-translational modifications, especially glycosylation. To date, it remains elusive whether the glycosylation contributes to the regulation of BK channels by ß1 subunits. Methods: Herein, we combined the electrophysiological approach with molecular mutations and biochemical manipulation to investigate the function roles of N-glycosylation in ß1 subunits. Results: The results show that deglycosylation of ß1 subunits through double-site mutations (ß1 N80A/N142A or ß1 N80Q/N142Q) could significantly increase the inhibitory potency of iberiotoxin, a specific BK channel blocker. The deglycosylated channels also have a different sensitivity to martentoxin, another BK channel modulator with some remarkable effects as reported before. On the contrary to enhancing effects of martentoxin on glycosylated BK channels under the presence of cytoplasmic Ca2+, deglycosylated channels were not affected by the toxin. However, the deglycosylated channels were surprisingly inhibited by martentoxin under the absence of cytoplasmic Ca2+, while the glycosylated channels were not inhibited under this same condition. In addition, wild type BK (α+ß1) channels treated with PNGase F also showed the same trend of pharmacological results to the mutants. Similar to this modulation of glycosylation on BK channel pharmacology, the deglycosylated forms of the channels were activated at a faster speed than the glycosylated ones. However, the V1/2 and slope were not changed by the glycosylation. Conclusion: The present study reveals that glycosylation is an indispensable determinant of the modulation of ß1-subunit on BK channel pharmacology and its activation. The loss of glycosylation of ß1 subunits could lead to the dysfunction of BK channel, resulting in a pathological state.(AU)
Asunto(s)
Glicosilación , Péptido-N4-(N-acetil-beta-glucosaminil) Asparagina Amidasa , Mutación , FarmacologíaRESUMEN
The accessory ß1 subunits, regulating the pharmacological and biophysical properties of BK channels, always undergo post-translational modifications, especially glycosylation. To date, it remains elusive whether the glycosylation contributes to the regulation of BK channels by ß1 subunits. Methods: Herein, we combined the electrophysiological approach with molecular mutations and biochemical manipulation to investigate the function roles of N-glycosylation in ß1 subunits. Results: The results show that deglycosylation of ß1 subunits through double-site mutations (ß1 N80A/N142A or ß1 N80Q/N142Q) could significantly increase the inhibitory potency of iberiotoxin, a specific BK channel blocker. The deglycosylated channels also have a different sensitivity to martentoxin, another BK channel modulator with some remarkable effects as reported before. On the contrary to enhancing effects of martentoxin on glycosylated BK channels under the presence of cytoplasmic Ca2+, deglycosylated channels were not affected by the toxin. However, the deglycosylated channels were surprisingly inhibited by martentoxin under the absence of cytoplasmic Ca2+, while the glycosylated channels were not inhibited under this same condition. In addition, wild type BK (α+ß1) channels treated with PNGase F also showed the same trend of pharmacological results to the mutants. Similar to this modulation of glycosylation on BK channel pharmacology, the deglycosylated forms of the channels were activated at a faster speed than the glycosylated ones. However, the V1/2 and slope were not changed by the glycosylation. Conclusion: The present study reveals that glycosylation is an indispensable determinant of the modulation of ß1-subunit on BK channel pharmacology and its activation. The loss of glycosylation of ß1 subunits could lead to the dysfunction of BK channel, resulting in a pathological state.(AU)
Asunto(s)
Glicosilación , Péptido-N4-(N-acetil-beta-glucosaminil) Asparagina Amidasa , Mutación , FarmacologíaRESUMEN
PURPOSE: To investigate the effect of sevoflurane preconditioning on ischemia/reperfusion (I/R)-induced pulmonary/hepatic injury. METHODS: Fifty-one Wistar rats were randomly grouped into sham, I/R, and sevoflurane groups. After reperfusion, the structural change of the lung was measured by Smith score, the wet and dry weights (W/D) were determined, malondialdehyde (MDA) myeloperoxidase (MPO) content was determined colorimetrically and by fluorescence, respectively, and matrix metalloprotein-9 (MMP-9) mRNA was quantified by RT-PCR. Biopsy and morphological analyses were performed on liver tissue, activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were determined, and tumor necrosis factor-alpha (TNF-α) level was determined. RESULTS: The sham group showed no changes in tissue structure. Structural lesions in the sevoflurane and I/R groups were mild and severe, respectively. Smith score, W/D, MDA, MPO, and MMP mRNA showed the same trend, and were increased in the I/R group and recovered in the sevoflurane group, compared with the sham group (both P<0.05). AST and ALT were significantly increased compared to the sham group (AST: 655±52.06 vs . 29±9.30 U/L; ALT: 693±75.56 vs . 37±6.71 U/L; P<0.05). In the sevoflurane group, AST and ALT levels were significantly decreased (464±47.71 and 516±78.84 U/L; P<0.001). TNF-α presented similar results. CONCLUSION: The protection of lung and liver by sevoflurane may be mediated by inhibited leukocyte recruitment and MMP-9 secretion.
Asunto(s)
Anestésicos por Inhalación/uso terapéutico , Precondicionamiento Isquémico/métodos , Hígado/irrigación sanguínea , Pulmón/irrigación sanguínea , Daño por Reperfusión/prevención & control , Sevoflurano/uso terapéutico , Alanina Transaminasa/sangre , Animales , Aspartato Aminotransferasas/sangre , Modelos Animales de Enfermedad , Isquemia/prevención & control , Hígado/efectos de los fármacos , Hígado/patología , Pulmón/efectos de los fármacos , Pulmón/patología , Masculino , Malondialdehído/análisis , Peroxidasa/análisis , Ratas , Ratas Wistar , Daño por Reperfusión/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/sangreRESUMEN
Abstract Purpose To investigate the effect of sevoflurane preconditioning on ischemia/reperfusion (I/R)-induced pulmonary/hepatic injury Methods Fifty-one Wistar rats were randomly grouped into sham, I/R, and sevoflurane groups. After reperfusion, the structural change of the lung was measured by Smith score, the wet and dry weights (W/D) were determined, malondialdehyde (MDA) myeloperoxidase (MPO) content was determined colorimetrically and by fluorescence, respectively, and matrix metalloprotein-9 (MMP-9) mRNA was quantified by RT-PCR. Biopsy and morphological analyses were performed on liver tissue, activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were determined, and tumor necrosis factor-alpha (TNF-α) level was determined. Results The sham group showed no changes in tissue structure. Structural lesions in the sevoflurane and I/R groups were mild and severe, respectively. Smith score, W/D, MDA, MPO, and MMP mRNA showed the same trend, and were increased in the I/R group and recovered in the sevoflurane group, compared with the sham group (both P<0.05). AST and ALT were significantly increased compared to the sham group (AST: 655±52.06 vs . 29±9.30 U/L; ALT: 693±75.56 vs . 37±6.71 U/L; P<0.05). In the sevoflurane group, AST and ALT levels were significantly decreased (464±47.71 and 516±78.84 U/L; P<0.001). TNF-α presented similar results. Conclusion The protection of lung and liver by sevoflurane may be mediated by inhibited leukocyte recruitment and MMP-9 secretion.(AU)
Asunto(s)
Animales , Ratas , Sevoflurano/administración & dosificación , Sevoflurano/uso terapéutico , Lesión Pulmonar/terapia , Hígado/lesiones , Daño por ReperfusiónRESUMEN
Abstract Purpose To investigate the effect of sevoflurane preconditioning on ischemia/reperfusion (I/R)-induced pulmonary/hepatic injury Methods Fifty-one Wistar rats were randomly grouped into sham, I/R, and sevoflurane groups. After reperfusion, the structural change of the lung was measured by Smith score, the wet and dry weights (W/D) were determined, malondialdehyde (MDA) myeloperoxidase (MPO) content was determined colorimetrically and by fluorescence, respectively, and matrix metalloprotein-9 (MMP-9) mRNA was quantified by RT-PCR. Biopsy and morphological analyses were performed on liver tissue, activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were determined, and tumor necrosis factor-alpha (TNF-α) level was determined. Results The sham group showed no changes in tissue structure. Structural lesions in the sevoflurane and I/R groups were mild and severe, respectively. Smith score, W/D, MDA, MPO, and MMP mRNA showed the same trend, and were increased in the I/R group and recovered in the sevoflurane group, compared with the sham group (both P<0.05). AST and ALT were significantly increased compared to the sham group (AST: 655±52.06 vs . 29±9.30 U/L; ALT: 693±75.56 vs . 37±6.71 U/L; P<0.05). In the sevoflurane group, AST and ALT levels were significantly decreased (464±47.71 and 516±78.84 U/L; P<0.001). TNF-α presented similar results. Conclusion The protection of lung and liver by sevoflurane may be mediated by inhibited leukocyte recruitment and MMP-9 secretion.
Asunto(s)
Animales , Masculino , Ratas , Daño por Reperfusión/prevención & control , Anestésicos por Inhalación/uso terapéutico , Precondicionamiento Isquémico/métodos , Hígado/irrigación sanguínea , Pulmón/irrigación sanguínea , Aspartato Aminotransferasas/sangre , Daño por Reperfusión/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/sangre , Peroxidasa/análisis , Alanina Transaminasa/sangre , Modelos Animales de Enfermedad , Sevoflurano/uso terapéutico , Isquemia/prevención & control , Hígado/efectos de los fármacos , Hígado/patología , Pulmón/efectos de los fármacos , Pulmón/patología , Malondialdehído/análisisRESUMEN
BACKGROUND: To compare the survival of Chinese cirrhotic patients with hepatocellular carcinoma (HCC) ≤ 4 cm who underwent radiofrequency ablation (RFA) alone or a combination of RFA with percutaneous ethanol injection (PEI). MATERIAL AND METHODS: Retrospective analysis was performed for 681 cases with HCC ≤ 4 cm who were treated with RFA alone or RFA combined with PEI (RFA + PEI) between 2004 and 2011. RESULTS: As a result, 180 patients in each group were selected after propensity score matching (PSM). Higher overall survival (OS) and recurrence-free survival (RFS) rates were achieved by RFA + PEI compared with RFA alone (P = 0.019 and 0.009, respectively). The 1-, 3-, and 5-year cumulative OS rates were 78.0, 44.4, and 30.1% for patients in RFA group and 88.2, 58.0, and 41.1% for patients in RFA + PEI group, respectively. Besides, the 1-, 3-, and 5-year cumulative RFS rates were 77.0, 43.8, and 29.2% in RFA group, and 87.9, 57.6, and 38.4% in RFA + PEI group, respectively. The local recurrence, complete ablation and five-year mortality showed no distinct differences between RFA and RFA + PEI groups in three subgroups classified with tumor size. Moreover, Cox regression multivariate analysis results showed that sex and treatment approach were significantly related to OS, whereas sex, status of HBsAg, local recurrence, and number of tumor nodule were related to RFS. CONCLUSION: Therefore, the combination of RFA and PEI yielded better OS and RFS rates than RFA alone for Chinese patients with HCC ≤ 4 cm.
Asunto(s)
Carcinoma Hepatocelular/cirugía , Ablación por Catéter , Etanol/administración & dosificación , Neoplasias Hepáticas/cirugía , Adulto , Anciano , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Ablación por Catéter/efectos adversos , Ablación por Catéter/mortalidad , Distribución de Chi-Cuadrado , China , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Etanol/efectos adversos , Femenino , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Recurrencia Local de Neoplasia , Puntaje de Propensión , Modelos de Riesgos Proporcionales , Sistema de Registros , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Carga TumoralRESUMEN
BACKGROUND: We hypothesized that combination of dendritic cell (DC) with autologous cytokine-induced killer (CIK) immunotherapy in setting of high-dose chemotherapy (HDC) would be effective for selected metastatic breast cancer (MBC) patients. PATIENTS AND METHODS: Our previous work showed thiotepa could eradicate breast cancer stem cells. From 2004 to 2009, 79 patients received standard dose chemotherapy (SDC) of 75 mg/m(2) docetaxel and 75 mg/m(2) thiotepa versus 87 patients of HDC + DC/CIK: 120 mg/m(2) docetaxel to mobilize peripheral CD34(+) progenitor cells, a sequence of HDC (120 mg/m(2) docetaxel, plus 175 mg/m(2) thiotepa) + DC/CIK, with or without 400 mg/m(2) carboplatin depending upon bone marrow function. The endpoints were response rates (RR), progression-free survival (PFS), and overall survival (OS). RESULTS: Compared with SDC, PFS and OS were improved in HDC + DC/CIK (median PFS 10.2 vs. 3.7 months, P < 0.001; median OS 33.1 vs. 15.2 months, P < 0.001). Patients of pre-menopausal, HDC as first-line treatment after metastasis, or with visceral metastasis showed prolonged PFS and OS. SDC group also achieved the similar response as previous reports. CONCLUSION: Our study demonstrated the novel combination of HDC with DC/CIK to be an effective choice for the selected MBC population, in which choosing appropriate chemo regimens played important roles, and also specific HDC regimen plus DC/CIK immunotherapy showed the clinical benefits compared with chemotherapy alone.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/mortalidad , Carcinoma Ductal de Mama/mortalidad , Carcinoma Lobular/mortalidad , Células Asesinas Inducidas por Citocinas/trasplante , Células Dendríticas/trasplante , Inmunoterapia Adoptiva , Adulto , Anciano , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Carboplatino/administración & dosificación , Carcinoma Ductal de Mama/secundario , Carcinoma Ductal de Mama/terapia , Carcinoma Lobular/secundario , Carcinoma Lobular/terapia , Terapia Combinada , Células Asesinas Inducidas por Citocinas/inmunología , Células Dendríticas/inmunología , Docetaxel , Femenino , Estudios de Seguimiento , Humanos , Dosis Máxima Tolerada , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Tasa de Supervivencia , Taxoides/administración & dosificación , Tiotepa/administración & dosificaciónRESUMEN
BACKGROUND: Recent studies suggest that the relationship between cancer stem cells (CSCs) and the vascular niche may be bidirectional; the niche can support the growth and renewal of CSCs, and CSCs may contribute to the maintenance of the niche. There is little knowledge concerning the role of breast cancer stem cells in promoting tumor angiogenesis. AIM: For human breast cancers, CSCs have been shown to be associated with a CD44+/CD24- phenotype. We investigated the potential activities of CD44+/CD24- breast cancer stem cells in promoting tumor angiogenesis. METHODS: The expression of pro-angiogenic genes was determined by quantitative real-time RT-PCR. Endothelial cell migration assays were employed to evaluate effects of conditioned media from CD44+/CD24- on human umbilical vein endothelial cells. A chorioallantoic membrane (CAM) assay was used to study the potential of CD44+/CD24- cells to promote angiogenesis. RESULTS: In our study, CD44+/CD24- cells expressed elevated levels of pro-angiogenic factors compared with CD44+/CD24+ cells. CD44+/CD24- cell-conditioned media significantly increased endothelial cell migration. Breast cancer cell lines enriched with CD44+/CD24- cells were more pro-angiogenic in the CAM assay than those lacking a CD44+/CD24- subpopulation. CD44+/CD24- cells sorted from MCF-7 cell lines were more pro-angiogenic in a CAM assay than CD44+/CD24+ cells. Furthermore, the VEGF concentration was significantly higher in CD44+/CD24- cell-conditioned media than in CD44+/CD24+ cell-conditioned media. The pro-angiogenic effect of CD44+/CD24- cells on endothelial cells was abolished by bevacizumab. CONCLUSION: Our findings demonstrate that CD44+/CD24- breast cancer stem cells have substantial pro-angiogenic potential and activity. This provides new insights to explore in the development of targeted therapies.
Asunto(s)
Neoplasias de la Mama/patología , Antígeno CD24/metabolismo , Receptores de Hialuranos/metabolismo , Células Madre Neoplásicas/patología , Neovascularización Patológica/metabolismo , Inhibidores de la Angiogénesis/farmacología , Animales , Anticuerpos Monoclonales Humanizados/farmacología , Bevacizumab , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Movimiento Celular , Embrión de Pollo , Membrana Corioalantoides/irrigación sanguínea , Membrana Corioalantoides/metabolismo , Resistencia a Antineoplásicos , Células Endoteliales/efectos de los fármacos , Células Endoteliales/fisiología , Femenino , Humanos , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/metabolismo , Neovascularización Patológica/patología , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
AIM: This study was designed to explore the genetic polymorphism of IL-10 (-1082A/G, -592A/C, -819T/C), TNF-α (-308G/A) with susceptibility to docetaxel-induced liver injury (DILI) in Chinese breast cancer patients. METHODS: The targeted genetic polymorphisms of IL10-1082G/A, IL10-592A/C, IL10-819T/C, TNF-308G/A from 40 patients with DILI were assayed by matrix-assisted laser desorption/ionization-time of flight of Sequenom. RESULTS: AA genotype of IL10-592 and TT of IL10-819 significantly increased incidence of DILI (P = 0.005, OR = 3.137). No differences of TNF gene polymorphism between the two groups were seen. CONCLUSION: The genetic polymorphism of the IL10-592A/C AA genotype and IL10-819T/C TT genotype was predominantly conferred to the incidence of docetaxel-induced liver injury.
Asunto(s)
Antineoplásicos/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/genética , Interleucina-10/genética , Taxoides/efectos adversos , Adulto , Anciano , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/genética , Estudios de Casos y Controles , Enfermedad Hepática Inducida por Sustancias y Drogas/epidemiología , Docetaxel , Femenino , Frecuencia de los Genes , Humanos , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/fisiología , Taxoides/uso terapéutico , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
PURPOSE: To ascertain the biologic significance of lung cancer Side population (SP) cells, which represent putative cancer stem cells (CSC) in the absence of consensus biomarkers for tumor-specific CSC. MATERIALS AND METHODS: We sorted and analyzed the angiogenic features of SP cells, isolated from tumor cell lines based on the exclusion of the DNA dye Hoechst 33342, from the NSCLC cell lines A549 and H460. RESULTS: Compared with non-SP cells, mRNA of vascular endothelial growth factor (VEGF)-A, VEGF-B, angiopoietin (ang)-1, ang-2, fibroblast growth factor-2 (FGF-2), cyclooxygenase-2 (Cox-2) and interleukin-8 (IL-8) were over-expressed in SP cells accompanied by over-expression of ABCG2 and MDR1 mRNA. The supernatant of cultured SP cells could significantly induce migration of human umbilical vein endothelial cells, while recombinant human endostatin (Endostar 25(®)) could inhibit the migration. CONCLUSIONS: This study revealed that the NSCLC SP cells might represent CSCs and possess pro-angiogenic properties, and antiangiogenesis represent a potential therapy.
Asunto(s)
Antineoplásicos/farmacología , Carcinoma de Pulmón de Células no Pequeñas/patología , Endostatinas/farmacología , Neoplasias Pulmonares/patología , Células Madre Neoplásicas/efectos de los fármacos , Neovascularización Patológica/patología , Células de Población Lateral/efectos de los fármacos , Subfamilia B de Transportador de Casetes de Unión a ATP , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , Transportadoras de Casetes de Unión a ATP/genética , Transportadoras de Casetes de Unión a ATP/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/irrigación sanguínea , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Línea Celular Tumoral , Ciclooxigenasa 2/metabolismo , Humanos , Neoplasias Pulmonares/irrigación sanguínea , Neoplasias Pulmonares/metabolismo , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Células Madre Neoplásicas/patología , Neovascularización Patológica/tratamiento farmacológico , Fenotipo , ARN Mensajero/metabolismo , Proteínas Recombinantes/farmacología , Células de Población Lateral/patologíaRESUMEN
AIM: The aim of the study is to explore the safety of cytotoxic T lymphocytes (CTLs) infusion by transfected dendritic cells (DCs) with recombinant adeno-associated virus vector (rAAV) carrying CEA cDNA among advanced cancer patients. PATIENTS AND METHODS: A total of 27 cancer patients with tumor tissue expression positivity and/or sera-elevated level of CEA were subsequently divided into cohort A and B resulted from the ex vivo expansion number of CTLs generated from co-culture of specific transfected DCs with autologous T lymphocytes. Based on the variations of infused number of specific CTL derived from different yields of individualized patients who had experienced various anti-cancer treatments, we compared the patients of low number of CTL cells (2-8 × 10(8) infused, cohort A, 6 cases) with those of higher number (above 8 × 10(8) infused, cohort B, 21 cases) to testify the possible adverse reactions caused by amount of infused CTLs. This study resembled a phase I study aiming for setting up clinical trial of adoptive cellular therapy that conceptually comes from conventional cytotoxic drugs. RESULTS: The results showed that one case from the each cohort had experienced moderate fever, and four cases with fatigue were seen in cohort B. The symptoms were transient without serious adverse events. For the consideration of clinical response 2 partial remission (8.0 %, 2/25), 1 minor remission, and 9 stable disease (40 %, 10/25) were observed in 25 patients eligible for evaluation. Sera levels of CEA assay were lowered in six patients. During a median follow-up of 8.1 months, we could not observe severe or chronic adverse reactions related to rAAV-DC infusions. Meanwhile, the variation of number of CTLs infused in this setting did not alter the status of peripheral lymphocyte population. CONCLUSIONS: These preliminary data suggest that the rAAV-DC immunotherapy is well-tolerated and showed no severe adverse reactions in cancer patients.
Asunto(s)
Vacunas contra el Cáncer/efectos adversos , Células Dendríticas/trasplante , Dependovirus/genética , Neoplasias/terapia , Linfocitos T Citotóxicos/trasplante , Adulto , Anciano , Vacunas contra el Cáncer/inmunología , Vacunas contra el Cáncer/metabolismo , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Femenino , Vectores Genéticos , Humanos , Inmunoterapia , Masculino , Persona de Mediana Edad , Neoplasias/inmunología , Neoplasias/metabolismo , Fenotipo , Linfocitos T Citotóxicos/inmunología , Linfocitos T Citotóxicos/metabolismo , TransfecciónRESUMEN
BACKGROUND: Increasing evidence shows that bone marrow stromal cells (BMSCs) have antitumor activities both in vitro and in animal models. Further studies fleshed out the supportive data that the antitumor activity of BMSCs could be markedly enhanced by cytokines such as IL-2 and IFN-ß (interferon). However, powerful strategies to activate BMSCs other than by genetically engineering interventions are still required. METHODS: In this study, new methods of generating antitumor activities of murine marrow-originated MSCs pulsed with homologous tumor-derived exosomes (TEX) were explored to yield potent immune effectors against hepatocellular carcinoma cells in vitro. RESULTS: The results showed that BMSCs pulsed with exosomes and IFN-γ exhibited increased migration ability with a result of 163.22 ± 26.90 versus 129.89 ± 29.28 cells/HP by transwell determination (p < 0.05). The inhibition of homologous hepatocellular carcinoma cells line H(22) cells by exosomes pulsed BMSCs was significantly increased by 41.9 % compared with control (p < 0.05), and flow cytometry analysis showed that the cell cycle of H(22) cells was arrested in G(0)/G(1) phase. Meanwhile, western blot analysis showed that PCNA protein expression in the supernatant of H(22) cells was significantly decreased. CONCLUSIONS: This study demonstrated that BMSCs pulsed with TEX could enhance its antitumor activities, which might be regarded as a novel promising antitumor treatment.
Asunto(s)
Carcinoma Hepatocelular/patología , Proliferación Celular , Exosomas/fisiología , Neoplasias Hepáticas/patología , Células Madre Mesenquimatosas/fisiología , Animales , Técnicas de Cultivo de Célula , Diferenciación Celular/fisiología , Linaje de la Célula/fisiología , Células Cultivadas , Regulación hacia Abajo , Exosomas/patología , Masculino , Ratones , Ratones Endogámicos BALB C , FenotipoRESUMEN
OBJECTIVES: The aim of the study was to determine rates of mask-wearing, of respiratory infection and the factors associated with mask-wearing and of respiratory infection in healthcare workers (HCWs) in Beijing during the winter of 2007/2008. METHODS: We conducted a survey of 400 HCWs working in eight hospitals in Beijing by face to face interview using a standardized questionnaire. RESULTS: We found that 280/400 (70.0%) of HCWs were compliant with mask-wearing while in contact with patients. Respiratory infection occurred in 238/400 (59.5%) subjects from November, 2007 through February, 2008. Respiratory infection was higher among females (odds ratio [OR], 2.00 [95% confidence interval {CI}, 1.16-3.49]) and staff working in larger hospitals (OR, 1.72 [95% CI, 1.092.72]), but was lower among subjects with seasonal influenza vaccination (OR, 0.46 [95% CI, 0.280.76]), wearing medical masks (reference: cotton-yarn; OR, 0.60 [95% CI, 0.39-0.91]) or with good mask-wearing adherence (OR, 0.60 [95% CI, 0.37-0.98]). The risk of respiratory infection of HCWs working in low risk areas was similar to that of HCWs in high risk area. CONCLUSION: Our data suggest that female HCWs and staffs working in larger hospitals are the focus of prevention and control of respiratory infection in Beijing hospitals. Mask-wearing and seasonal influenza vaccination are protective for respiratory infection in HCWs; the protective efficacy of medical masks is better than that of cotton yarn ones; respiratory infection of HCWs working in low risk areas should also be given attention.
Asunto(s)
Personal de Salud/estadística & datos numéricos , Transmisión de Enfermedad Infecciosa de Paciente a Profesional/prevención & control , Máscaras/estadística & datos numéricos , Infecciones del Sistema Respiratorio/prevención & control , Adulto , China , Femenino , Humanos , Transmisión de Enfermedad Infecciosa de Paciente a Profesional/estadística & datos numéricos , Masculino , Infecciones del Sistema Respiratorio/transmisión , Factores de Riesgo , Estaciones del Año , Factores Sexuales , Encuestas y CuestionariosRESUMEN
OBJECTIVES: The aim of the study was to determine rates of mask-wearing, of respiratory infection and the factors associated with mask-wearing and of respiratory infection in healthcare workers (HCWs) in Beijing during the winter of 2007/2008. METHODS: We conducted a survey of 400 HCWs working in eight hospitals in Beijing by face to face interview using a standardized questionnaire. RESULTS: We found that 280/400 (70.0 percent) of HCWs were compliant with mask-wearing while in contact with patients. Respiratory infection occurred in 238/400 (59.5 percent) subjects from November, 2007 through February, 2008. Respiratory infection was higher among females (odds ratio [OR], 2.00 [95 percent confidence interval {CI}, 1.16-3.49]) and staff working in larger hospitals (OR, 1.72 [95 percent CI, 1.092.72]), but was lower among subjects with seasonal influenza vaccination (OR, 0.46 [95 percent CI, 0.280.76]), wearing medical masks (reference: cotton-yarn; OR, 0.60 [95 percent CI, 0.39-0.91]) or with good mask-wearing adherence (OR, 0.60 [95 percent CI, 0.37-0.98]). The risk of respiratory infection of HCWs working in low risk areas was similar to that of HCWs in high risk area. CONCLUSION: Our data suggest that female HCWs and staffs working in larger hospitals are the focus of prevention and control of respiratory infection in Beijing hospitals. Mask-wearing and seasonal influenza vaccination are protective for respiratory infection in HCWs; the protective efficacy of medical masks is better than that of cotton yarn ones; respiratory infection of HCWs working in low risk areas should also be given attention.