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Proton pump inhibitors (PPIs) are often prescribed in association with clopidogrel and aspirin to patients with myocardial infraction (MI), but their effects on heart is controversial. The purpose of this study was to investigate the effects and potential mechanism of omeprazole (OME) and esomeprazole (ESO) in myocardial ischemia reperfusion (I/R) injury. In the present study, mice were treated with OME, ESO or vehicle for 3 weeks and then subjected to myocardial I/R or sham surgery. At 1 day after surgery, echocardiography was performed to access cardiac injury. Hematoxylin and eosin (H&E) staining was performed to evaluate cardiomyocyte morphology. The IL1ß was evaluated by Immunohistochemistry (IHC). Elisa was used to detect cTnt content in serum. The expression of CD86, CD206, CHOP, ATF6, eIF2α and p eIF2α were determined by Western blot (WB). The result showed that ESO markedly improved the left ventricular ejection fraction (LVEF), shortening fraction (FS), suppressed inflammatory infiltration, endoplasmic reticulum stress (ERS) and decreased proinflammatory macrophages in I/R hearts, while OME had no significant effects on cardiac function, inflammation and ERS in the I/R heart. In conclusion, ESO but not OME pretreatment reduces the proportion of proinflammatory macrophages, inhibits endoplasmic reticulum stress, and alleviates I/R injury in mice, indicating that ESO maybe a more proper PPI than OME for application in I/R injury.
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Daño por Reperfusión Miocárdica , Daño por Reperfusión , Animales , Apoptosis , Estrés del Retículo Endoplásmico , Esomeprazol/farmacología , Esomeprazol/uso terapéutico , Ratones , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Daño por Reperfusión Miocárdica/metabolismo , Miocitos Cardíacos/metabolismo , Volumen Sistólico , Función Ventricular IzquierdaRESUMEN
PURPOSE: Long-term failure of vein grafts due to neointimal hyperplasia remains an important problem in coronary artery bypass graft surgery. Endothelial to mesenchymal transition (EndMT) contributes to vein graft vascular remodeling. However, there is little study on microRNA-mediated EndMT contributions to neointimal formation in vein graft. We hypothesized that microRNA-92a (miR-92a) might play an important role in determining EndMT contributions to neointimal formation. METHODS: miR-92a and EndMT-related proteins detected by qRT-PCR and Western blot in vitro and in vivo. Adeno-associated virus 6 (AAV6) delivery gene therapy was used to inhibit neointimal formation in vivo. The intimal hyperplasia of vein grafts was measured by HE staining, the expression of EndMT-related protein in vein grafts was measured by immunofluorescence. Immunohistochemistry and luciferase assay were used to detect potential targets of miR-92a. RESULTS: The expression of miR-92a was found to be upregulated in neointimal hyperplasic lesions after vein grafting. Using cultured human umbilical vein endothelial cells (HUVECs), we show that TGF-ß1 treatment of HUVECs significantly increased miR-92a expression and induced EndMT, characterized by suppression of endothelial-specific markers (CD31 and VE-cadherin) and an increase in mesenchymal-specific markers (a-SMA and vimentin), while inhibition of miR-92a expression blunted EndMT in cultured HUVECs. Furthermore, AAV6 mediated miR-92a suppression gene therapy effectively resulted in decreased EndMT and less neointimal formation in vein grafts in vivo. We further identified that integrin alpha 5 (ITGA5) is a potential target gene involved in the development of neointima formation in these vein grafts. CONCLUSION: This data suggests that neointimal formation does not solely rely on vascular smooth muscle cell phenotypic switching but is also related to EndMT, and miR-92a-mediated EndMT is an important mechanism underlying neointimal formation in vein grafts.
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Endotelio/metabolismo , MicroARNs/metabolismo , Neointima/metabolismo , Animales , Células Cultivadas , Modelos Animales de Enfermedad , Transición Epitelial-Mesenquimal , Femenino , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , MicroARNs/genética , Neointima/patología , Ratas , Ratas Sprague-Dawley , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
It has been reported that chemokine CX3 CL1 can regulate various tumours by binding to its unique receptor CX3 CR1. However, the effect of CX3 CL1-CX3 CR1 on the lung adenocarcinoma and lung squamous cell carcinoma is still unclear. Here, we showed that CX3 CL1 can further invasion and migration of lung adenocarcinoma A549 and lung squamous cell carcinoma H520. In addition, Western blot and immunofluorescence test indicated CX3 CL1 up-regulated the phosphorylation level of cortactin, which is a marker of cell pseudopodium. Meanwhile, the phosphorylation levels of c-Src and c-Abl, which are closely related to the regulation of cortactin phosphorylation, are elevated. Nevertheless, the src/abl inhibitor bosutinib and mutations of cortactin phosphorylation site could inhibit the promotion effect of CX3 CL1 on invasion and migration of A549 and H520. Moreover, these results of MTT, Hoechst staining and Western blot suggested that CX3 CL1 had no effect on the proliferation and apoptosis of A549 and H520 in vitro. The effects of CX3 CL1 were also verified by the subcutaneous tumour formation in nude mice, which showed that it could promote proliferation and invasion of A549 in vivo. In summary, our results indicated that CX3 CL1 furthered invasion and migration in lung cancer cells partly via activating cortactin, and CX3 CL1 may be a potential molecule in regulating the migration and invasion of lung cancer.
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Quimiocina CXCL1/metabolismo , Cortactina/metabolismo , Neoplasias Pulmonares/metabolismo , Fosfotirosina/metabolismo , Animales , Apoptosis , Receptor 1 de Quimiocinas CX3C/metabolismo , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Humanos , Neoplasias Pulmonares/patología , Masculino , Ratones Desnudos , Invasividad Neoplásica , Fosforilación , Proteínas Proto-Oncogénicas c-abl/metabolismo , Transducción de Señal/efectos de los fármacos , Familia-src Quinasas/metabolismoRESUMEN
Atrial fibrosis plays a critical role in atrial fibrillation (AF) by the transforming growth factor (TGF)-ß1/Smad pathway. The disordered differentiation, proliferation, migration and collagen deposition of atrial fibroblasts play significant roles in atrial fibrosis. Mitsugumin (MG)53 is predominantly expressed in myocardium of rodents and has multiple biological functions. However, the role of MG53 in cardiac fibrosis remains unclear. This study provided clinical and experimental evidence for the involvement of MG53 in atrial fibrosis in humans and atrial fibrosis phenotype in cultured rat atrial fibroblasts. In atrial tissue from patients we demonstrated that MG53 was expressed in human atrium. Expression of MG53 increased with the extent of atrial fibrosis, which could induce AF. In cultured atrial fibroblasts, depletion of MG53 by siRNA caused down-regulation of the TGF-ß1/Smad pathway, while overexpression of MG53 by adenovirus up-regulated the pathway. MG53 regulated the proliferation and migration of atrial fibroblasts. Besides, exogenous TGF-ß1 suppressed expression of MG53. In conclusion, we demonstrated that MG53 was expressed in human atrium, and may be a potential upstream of the TGF-ß1/Smad pathway in human atrium and rat atrial fibroblasts. This suggests that MG53 is a potential regulator of atrial fibrosis induced by the TGF-ß1/Smad pathway in patients with AF.
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Fibrilación Atrial/genética , Fibrosis/genética , Proteínas Musculares/genética , Miocardio/metabolismo , Factor de Crecimiento Transformador beta1/genética , Proteínas de Transporte Vesicular/genética , Adenoviridae/genética , Animales , Fibrilación Atrial/patología , Diferenciación Celular/genética , Movimiento Celular/genética , Proliferación Celular/genética , Células Cultivadas , Modelos Animales de Enfermedad , Fibrosis/patología , Regulación de la Expresión Génica , Atrios Cardíacos/metabolismo , Atrios Cardíacos/patología , Humanos , Miocardio/patología , ARN Interferente Pequeño/genética , Ratas , Proteínas Smad/genéticaRESUMEN
Molecular biomarkers that can be detected in easily accessible body fluids have been proposed as non-invasive, cost-effective, and useful tools for cancer diagnosis. Recently, extensive research has explored the involvement of the aberrant expression of microRNA-21 (miRNA-21, miR-21) in lung cancer. Inconsistent results, however, have prevented its widespread use in diagnosis. In light of this situation, our meta-analysis aimed to systematically determine whether aberrant miR-21 expression can distinguish patients with lung cancer from cancer-free controls with a high level of diagnostic accuracy. A comprehensive literature search for relevant studies published before December 23, 2013 was conducted in the MEDLINE, EMBASE, the Cochrane Library, and three Chinese databases. The pooled sensitivity, specificity and other parameters were used to assess the overall performance of miR-21-based assays. Statistical analysis was conducted using the STATA 11.0 software. Eleven research articles involving 676 patients with lung cancer and 529 healthy controls were considered eligible for inclusion in the present meta-analysis. The following summary parameters were calculated from all the included studies: sensitivity of 0.66 (95 % confidence interval [CI]: 0.57-0.74), specificity of 0.82 (95 % CI: 0.74-0.88), positive likelihood ratio (PLR) of 3.70 (95 % CI: 2.50-5.60), negative likelihood ratio (NLR) of 0.42 (95 % CI: 0.32-0.54); diagnostic odds ratio (DOR) of 9.00 (95 % CI: 5.00-16.00), and area under the curve (AUC) of 0.81 (95 % CI: 0.77-0.84). In addition, we added two pre-specified covariates (ethnicity and specimen types) to the bivariate model to assess their impact on the diagnostic value of miR-21 for lung cancer. Similar results were also observed in subgroup analyses, indicating a relatively low level of accuracy. The current meta-analysis indicates that a single miR-21 may not be sufficient to identify lung cancer and that more miRNAs should be used to detect lung carcinoma.
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Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , MicroARNs/genética , Diagnóstico Diferencial , Humanos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sensibilidad y EspecificidadRESUMEN
The aim of this study is to investigate the gene-environment interactions between the G48A polymorphism in the alcohol dehydrogenase-2 (ADH2) gene and environmental factors in determining the risk of esophageal cancer (EC). A literature search was conducted in the PubMed, Embase, Web of Science, Cochrane Library, and Google Scholar databases to indentify eligible studies published before November 1, 2013. We performed a meta-analysis of 18 case-control studies with a total of 8,906 EC patients and 13,712 controls. The overall analysis suggested that individuals with the GG genotype were associated with a 2.77-fold increased risk of EC, compared with carriers of the GA and AA genotypes. In a stratified analysis by ethnic group, Japanese, Mainland Chinese, and Taiwan Chinese with the GG genotype had a significantly higher risk of EC, compared with Thai and Iranian populations, indicating ethnic variance in EC susceptibility. An analysis of combined effect indicated that GG genotype of ADH2 G48A was associated with the highest risk of EC in heavy drinkers and smokers. A striking difference was found to exist between males and females, showing gender variance for the association between ADH2 G48A and EC risk. This meta-analysis shows that the GG genotype of ADH2 G48A may be associated with an increased risk of EC in Asian populations. In addition, significant gene-environment interactions were found. Heavy drinkers, smokers, and males with the GG genotype may have a higher EC risk. Thus, our results shed new light on the complex gene-environment interactions that exist between environmental factors and ADH2 G48A polymorphism in EC risk.
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Alcohol Deshidrogenasa/genética , Pueblo Asiatico/genética , Neoplasias Esofágicas/etiología , Interacción Gen-Ambiente , Polimorfismo Genético , Estudios de Casos y Controles , Neoplasias Esofágicas/etnología , Neoplasias Esofágicas/genética , Femenino , Genotipo , Humanos , Masculino , Sesgo de Publicación , Riesgo , Caracteres Sexuales , Fumar/efectos adversosRESUMEN
INTRODUCTION: This study aims to investigate the effect of concomitant tricuspid valve surgery (TVS) during left ventricular assist device (LVAD) implantation due to the controversy over the clinical outcomes of concomitant TVS in patients undergoing LVAD. METHODS: A systematic literature search was performed in PubMed and EMbase from the inception to 1 August 2023. Studies comparing outcomes in adult patients undergoing concomitant TVS during LVAD implantation (TVS group) and those who did not (no-TVS group) were included. The primary outcomes were right heart failure (RHF), right ventricular assist device (RVAD) implantation, and early mortality. All meta-analyses were performed using random-effects models, and a two-tailed P <0.05 was considered significant. RESULTS: Twenty-one studies were included, and 16 of them were involved in the meta-analysis, with 660 patients in the TVS group and 1291 in the no-TVS group. Patients in the TVS group suffered from increased risks of RHF [risk ratios (RR)=1.31, 95% CI: 1.01-1.70, P =0.04; I2 =38%, pH =0.13), RVAD implantation (RR=1.56, 95% CI: 1.16-2.11, P =0.003; I2 =0%, pH =0.74), and early mortality (RR=1.61, 95% CI: 1.07-2.42, P =0.02; I2 =0%, pH =0.75). Besides, the increased risk of RHF holds true in patients with moderate to severe tricuspid regurgitation (RR=1.36, 95% CI: 1.04-1.78, P =0.02). TVS was associated with a prolonged cardiopulmonary bypass time. No significant differences in acute kidney injury, reoperation requirement, hospital length of stay, or ICU stay were observed. CONCLUSIONS: Concomitant TVS failed to show benefits in patients undergoing LVAD, and it was associated with increased risks of RHF, RVAD implantation, and early mortality.
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Insuficiencia Cardíaca , Corazón Auxiliar , Válvula Tricúspide , Humanos , Válvula Tricúspide/cirugía , Insuficiencia Cardíaca/cirugía , Insuficiencia Cardíaca/mortalidad , Insuficiencia de la Válvula Tricúspide/cirugía , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Implantación de Prótesis de Válvulas Cardíacas/mortalidad , Implantación de Prótesis de Válvulas Cardíacas/instrumentaciónRESUMEN
Acute kidney injury (AKI) is a common postoperative complication, but there is still a lack of accurate biomarkers. Cardiac surgery-associated AKI is the most common cause of major-surgery-related AKI, and patients requiring renal replacement therapy have high mortality rates. Early diagnosis, intervention, and management are crucial for improving patient prognosis. However, diagnosing AKI based solely on changes in serum creatinine level and urine output is insufficient, as these changes often lag behind actual kidney damage, making early detection challenging. Biomarkers such as tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein-7 (IGFBP-7) have been found to be significant predictors of moderate-to-severe AKI when combined with urine content analysis. This article reviews the mechanism of biomarkers TIMP-2 and IGFBP-7 in AKI and provides a comprehensive overview of the clinical effects of TIMP-2 and IGFBP-7 in cardiac surgery-associated AKI, including prediction, diagnosis, and progression.
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Lesión Renal Aguda , Biomarcadores , Procedimientos Quirúrgicos Cardíacos , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina , Complicaciones Posoperatorias , Inhibidor Tisular de Metaloproteinasa-2 , Humanos , Inhibidor Tisular de Metaloproteinasa-2/sangre , Inhibidor Tisular de Metaloproteinasa-2/orina , Lesión Renal Aguda/etiología , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/sangre , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina/orina , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Biomarcadores/sangre , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/diagnóstico , PronósticoRESUMEN
OBJECTIVE: To explore the effects of reconstructing method (narrow gastric tube (NGT) versus whole stomach (WS)) on health-related quality of life (HRQL) in patients during a 3-year follow-up. METHODS: In a prospective randomized single-center study from 2007 to 2008, 104 patients underwent esophagectomy for cancer. They were divided into NGT (n = 52) and WS (n = 52) groups. To assess HRQL, a questionnaire in references to EORTC-QLQ-C30 and QLQ-OES18 was administered at 3 weeks, 6 months, 1 year, 2 year and 3 years post-operation. Their clinical data were collected prospectively and follow-up was performed regularly. RESULTS: The patients in the NGT group reported significantly (P < 0.05) better average scores of HRQL at both 6 months and 1 year.However, no significant difference in average scores of HRQL was found at 3 years. Patients in the NGT group reported significantly (P < 0.05) better scores of reflux at 3 weeks, 6 months and 1 year.Nausea was the only item with significant difference on HRQL at 2 years and 3 years.No significant difference existed between two groups with regards to cumulative survival rate at 3 years. CONCLUSION: No significant difference existed between two groups with regards to cumulative survival rate at 3 years. The patients with gastric tube reconstruction after oncologic esophagectomy present better HRQL.Further studies are warranted to perform survival analysis beyond 3 year post-operation.
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Neoplasias Esofágicas/cirugía , Procedimientos de Cirugía Plástica/métodos , Calidad de Vida , Adulto , Anciano , Esofagectomía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Encuestas y CuestionariosRESUMEN
Progranulin (PGRN) is a growth factor that is involved in the progression of multiple tumors. However, the effects and molecular mechanisms by which PGRN induces lung cancer remain unclear. The expression level of PGRN was analyzed by conducting immunohistochemistry of the histological sections of lung tissues from non-small-cell lung carcinoma (NSCLC) patients. The proliferation, apoptosis, migration, and invasion of NSCLC cells were assessed by the MTT assay, Western blot, degree of wound healing, and Transwell assays. A nude mouse xenograft model was used to validate the role of PGRN in vivo. The expression level of PGRN was higher in male patients with lung adenocarcinoma than in those with lung squamous cell carcinoma; by contrast, no difference was observed in female patients. The overexpression of PGRN promoted the proliferation and anti-apoptosis of H520 (derived from lung squamous cell carcinoma) cells, whereas knockdown of PGRN inhibited the proliferation and anti-apoptosis of A549 (derived from lung adenocarcinoma) cells. Copanlisib (targeting PI3K) inhibited the increase in the expression of cell anti-apoptosis marker Bcl-2 induced by rhPGRN protein; the PI3K agonist 740 Y-P partially reversed the decrease in Bcl-2 expression induced by PGRN deficiency in both A549 and H520 cells. PGRN increased the expression of Ki-67, PCNA, and Bcl-2 in vivo. PGRN inhibited cell apoptosis depending on the PI3K/Akt/Bcl-2 signaling axis; PGRN positivity correlated with lung adenocarcinoma. PGRN is a potential biomarker for the treatment and diagnosis of NSCLC, especially in lung adenocarcinoma.
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Unilateral pulmonary vein atresia is a rare abnormality that usually presents in infants with recurrent hemoptysis and pneumonia. Presentation in adulthood without additional congenital heart disease is rare but does occur. Anatomic variations in the pulmonary vessels that supply and drain the affected lung can explain the mildly symptomatic process. The diagnosis of isolated unilateral pulmonary vein atresia is usually made angiographically. Pneumonectomy is indicated once symptoms or complications are present so that irreversible pulmonary hypertension can be avoided.
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Venas Pulmonares/anomalías , Venas Pulmonares/cirugía , Procedimientos Quirúrgicos Vasculares/métodos , Adulto , Femenino , Humanos , Venas Pulmonares/diagnóstico por imagen , Radiografía , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: This study aims to investigate the efficacy and safety of heat and moisture exchanger on airway resistance in a cardiothoracic surgery intensive care unit. METHODS: A total of 31 patients (18 males, 13 females; mean age 51.5 years; range, 39 to 61 years) who were treated with long-term mechanical ventilation due to low cardiac output syndrome after cardiopulmonary bypass and cardiac surgery were retrospectively analyzed between December 2014 and December 2018. In addition, an in vitro lung model and different doses of hydroxyethyl starch in the heat and moisture exchangers to mimic the airway secretions were used and the proper interval to change heat and moisture exchangers was evaluated. RESULTS: In the in vitro l ung m odel, t he m ean a irway r esistance was 19.4±0.2 cmH2O/L/sec in the 5 mL group (p=0.060), 20.3±1.0 cmH2O/L/sec in the 10 mL group (p=0.065), and 30.2±1.7 cmH2O/L/sec in the 15 mL group (p<0.001). The airway resistance of heat and moisture exchangers, and total hospital stay and ventilation duration significantly increased in the seven-day group compared to the one-day and three-day groups. The positive culture of bacteria was also significantly higher in the seven-day group. CONCLUSION: Our study results suggest that heat and moisture exchangers can be safely used for an efficient and timely removal of airway secretions. Volume of approximately 15 mL of liquid in the airflow can dramatically increase the airway resistance. The three-day interval of changing heat and moisture exchangers is ideal in a cardiothoracic surgery intensive care unit where patients have more airway secretions than patients in the general intensive care unit.
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Gut microbiota can promote tumor development by producing toxic metabolites and inhibiting the function of immune cells. Previous studies have demonstrated that gut microbiota can reach the liver through the circulation and promote the occurrence of liver cancer. Ciprofloxacin, an effective broadspectrum antimicrobial agent, can promote cell apoptosis and regulate the function of immune cells. As an important part of the tumor microenvironment, macrophages play an important role in tumor regulation. The present study demonstrated that the treatment of macrophages with ciprofloxacin was able to promote the production of interleukin1ß, tumor necrosis factorα and the polarization of CD86+CD206 macrophages, while inhibiting the polarization of CD86CD206+ macrophages. This transformation may help macrophages promote tumor cell apoptosis, inhibit tumor cell proliferation, reduce metastasis and downregulate the phosphoinositide 3kinase/AKT signaling pathway in liver cancer cell lines. In vivo experiments demonstrated that macrophages treated with ciprofloxacin inhibited the growth of subcutaneous implanted tumors in nude mice. In conclusion, the findings of the present study indicated that ciprofloxacin may inhibit liver cancer by upregulating the expression of CD86+CD206 macrophages. This study further revealed the biological mechanism underlying the potential value of ciprofloxacin in antitumor therapy and provided new targets for the treatment of liver cancer.
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Antígeno B7-2/metabolismo , Ciprofloxacina/administración & dosificación , Neoplasias Hepáticas/tratamiento farmacológico , Macrófagos/inmunología , Glicoproteínas de Membrana/metabolismo , Receptores Inmunológicos/metabolismo , Línea Celular Tumoral , Polaridad Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Ciprofloxacina/farmacología , Células Hep G2 , Humanos , Interleucina-1beta/metabolismo , Neoplasias Hepáticas/inmunología , Macrófagos/efectos de los fármacos , Microambiente Tumoral/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
The health-related quality of life (HRQL) is generally accepted as an important parameter for patients undergoing oncologic surgery. We conducted this prospective, randomized study to compare the effect of narrow gastric tube (NGT) reconstruction and whole-stomach (WS) reconstruction on the long-term HRQL in patients after esophagectomy. One hundred and four patients undergoing esophagectomy were enrolled in our study from 2007 to 2008, with 52 in NGT group and 52 in WS group. A questionnaire with reference to the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-OES18 was used to assess the HRQL at 3 weeks, 6 months, 1, 2, 3, 4, and 5 years after esophagectomy. Data collection and follow-up were performed regularly. No significant difference was found between NGT group and WS group in the patients' baseline characteristics. Patients in NGT group had decreased risk of postoperative reflux esophagitis by comparison with those in WS group. The 5-year cumulative survival rate was 42 % (NGT) and 27 % (WS), respectively. Compared with WS group, a significant increased survival rate (P = 0.027) was found in NGT group. Additionally, patients had lower dysphagia scores (better) in NGT group than those in WS group at 5 years after esophagectomy (P < 0.05). However, the scores of the other scales did not show statistical difference at 5-year follow-up. NGT is a better option for the reconstruction after esophagectomy because of decreased risk of postoperative complication, increased survival rate, and better HRQL, and NGT should be preferred to be recommended for patients undergoing esophagectomy.
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Adenocarcinoma/cirugía , Carcinoma de Células Pequeñas/cirugía , Carcinoma de Células Escamosas/cirugía , Neoplasias Esofágicas/cirugía , Procedimientos de Cirugía Plástica/métodos , Complicaciones Posoperatorias , Calidad de Vida , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adulto , Anciano , Carcinoma de Células Pequeñas/mortalidad , Carcinoma de Células Pequeñas/patología , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Femenino , Estudios de Seguimiento , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Prospectivos , Encuestas y Cuestionarios , Tasa de SupervivenciaRESUMEN
In the bone morphogenetic protein (BMP) family, BMP9 is the strongest inducer of osteogenic differentiation in mesenchymal stem cells. Recent studies have suggested that the miR-30 family regulates cell proliferation and osteoblastic differentiation. In the present study, we found that expression of only one miR-30 family member, miR-30a, first decreased and then increased during BMP9-induced osteogenic differentiation. Cell proliferation assays revealed that miR-30a had no effect on the proliferation of C3H10T1/2 cells. However, over-expression of miR-30a led to expression of an early osteogenic marker and a reduction in Runx2 expression. In addition, we observed decreases in the expression of late osteogenic markers and osteopontin, as well as calcium deposition. Dual-luciferase reporter assays indicated that this process might be mediated by suppressing Runx2 protein expression. In vivo stem cell implantation revealed inhibition of BMP9-induced ectopic bone formation and matrix mineralization by miR-30a. This study provides a better understanding of the molecular mechanisms through which miR-30a negatively regulates BMP9-induced osteogenic differentiation.
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Diferenciación Celular/genética , Factor 2 de Diferenciación de Crecimiento/genética , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , MicroARNs/genética , Osteogénesis/genética , Animales , Diferenciación Celular/efectos de los fármacos , Línea Celular , Proliferación Celular/genética , Subunidad alfa 1 del Factor de Unión al Sitio Principal/química , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Expresión Génica , Factor 2 de Diferenciación de Crecimiento/farmacología , Humanos , Células Madre Mesenquimatosas/efectos de los fármacos , Ratones , MicroARNs/química , Osteogénesis/efectos de los fármacos , Interferencia de ARN , ARN Mensajero/química , ARN Mensajero/genéticaRESUMEN
Bone metastases from hepatocellular carcinoma (HCC) seem to be increasing. Previous studies showed that soluble factors secreted by host cells and direct cell-to-cell interactions contributed to the preferential metastasis and growth of cancer cells in bone, while the underlying mechanism(s) of the metastasis of HCC in the bone are poorly understood. Here, we determined the effect of HS-5 cells on Huh7 cell proliferation, and investigated the role of CCL5 from HS-5 cells on the development of Huh7 cells. In addition, the underlying mechanisms on the influence in Huh7 cells were investigated. Our results showed that HS-5 cells could promote the proliferation, migration and invasion of Huh7 cells, and inhibited apoptosis. CCL5 downregulation was able to inhibit the effects of HS-5 cells on Huh7 cell migration and invasion via the PI3K-Akt signaling pathway and reduce MMP-2 expression. Therefore, these findings suggest that CCL5 secreted from MSCs can promote the migration and invasion of Huh7 cells and could be an important factor in HCC related to occurrence of bone metastases.
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Carcinoma Hepatocelular/patología , Quimiocina CCL5/metabolismo , Neoplasias Hepáticas/patología , Animales , Células de la Médula Ósea/metabolismo , Línea Celular Tumoral , Movimiento Celular , Humanos , Neoplasias Hepáticas Experimentales , Sistema de Señalización de MAP Quinasas , Masculino , Ratones , Ratones SCID , Invasividad Neoplásica , Células del Estroma/metabolismoRESUMEN
OBJECTIVE: To investigate the effect of 1,25-dihydroxyvitamin D(3) and 5-fluorouracil, either alone or in combination, on the expression of IGFBP-3 in human esophageal carcinoma 109 cell xenograft in nude mice. METHODS: In vitro cultured esophageal carcinoma Eca-109 cells were inoculated subcutaneously in BALB/c mice. The tumor-bearing mice were randomly divided into control group (A), 1,25-dihydroxyvitamin D(3) group (B), 5-fluorouracil group (C), and 1,25-dihydroxyvitamin D(3) plus 5-fluorouracil group (D). 1,25-dihydroxyvitamin D(3) and 5-fluorouracil were administered at the doses of 2.5 ug/kg and 25 mg/kg via intraperitoneal injections, respectively, and the mice in the control group received saline injection only. The tumor growth was observed and the expression of IGFBP-3 in the tumor xenograft was detected using immunohistochemistry. An automatic biochemistry analyzer was used to determine serum calcium levels, and Von Kossa staining was utilized for observation of calcium deposition in the kidneys. RESULTS: Compared with that in group A, the xenograft in groups B, C, and D all showed a lowered growth rate with a smaller tumor volume, and presented with stronger IGFBP-3 positivity and significantly higher levels of IGFBP-3 protein expression (P<0.05). In group D, the protein expression of IGFBP-3 was significantly increased compared with that in groups B and C (P<0.05). Compared with that in group A, serum calcium level was slightly increased in groups B, C, and D, , but no obvious calcium deposition was found in the kidney tissue sections. CONCLUSION: Both 1,25-dihydroxyvitamin D(3) and 5-fluorouracil can inhibit the growth of the tumor xenograft in nude mice, and their combination is more effective. This effect is probably associated with increased protein expression of IGFBP-3 in the xenograft tumor. No calcium deposition occurs in the kidney tissue of the tumor-bearing mice.
Asunto(s)
Fluorouracilo/farmacología , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Vitamina D/análogos & derivados , Ensayos Antitumor por Modelo de Xenoinjerto , Animales , Línea Celular Tumoral , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Vitamina D/farmacologíaRESUMEN
OBJECTIVE: For patients undergoing oncologic surgery, the quality of life (QoL) is generally accepted as an important outcome parameter in addition to long-term survival, mortality and complication rates. This study focussed on the QoL in patients after oesophagectomy for cancer, comparing the method of reconstruction (narrow gastric tube vs whole stomach). METHODS: In a prospective randomised single-centre study from 2007 to 2008, 104 patients underwent oesophagectomy for cancer. To assess the QoL, a questionnaire in reference to the EORTC-QLQ-C30 and the QLQ-OES24 was administered at 3 weeks, 6 months and 1 year after surgery. Clinical data were collected prospectively, and follow-up was performed regularly. RESULTS: There were no significant differences between the narrow gastric tube group (NGT group, n=52) and the whole-stomach group (WS group, n=52) with regard to patient and cancer characteristics, operative procedure, postoperative intensive care unit (ICU) hospitalisation, and overall survival at 1 year. Regarding the postoperative complication, there were more cases of postoperative reflux oesophagitis and impairment of pulmonary function in the WS group (P<0.05). Regarding the QoL investigation, the scores of QoL dropped for all patients at 3 weeks after surgery. Slowly, recovery was found at both 6 months and 1 year in both groups. Patients in the NGT group reported significantly (P<0.05) better scores of QoL at both 6 months and 1 year. CONCLUSIONS: Patients who underwent gastric tube reconstruction develop less postoperative digestive tract complications, and have a quicker recovery and a better QoL during the follow-up period. Further investigation and data collection will allow the assessment of this procedure beyond 1 year after operation.