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This article explores the "On-Demand Health Education System" in healthcare, highlighting its role in enhancing nursing efficiency and quality. Using a database, it allows nurses to provide tailored education via QR codes for patients and families. Key findings show its positive impact on education quality and efficiency, though improvements are needed in user interface and accessibility for certain groups like the elderly. Future enhancements should focus on user experience and expanding accessibility, acknowledging the potential of such systems in medical education with technological advancement.
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Carga de Trabajo , Humanos , Educación en Enfermería , Instrucción por Computador/métodosRESUMEN
SCOPE: Kaempferol (KMP), a bioactive flavonoid compound found in fruits and vegetables, contributes to human health in many ways but little is known about its relationship with muscle mass. The effect of KMP on C2C12 myoblast differentiation and the mechanisms that might underlie that effect are studied. METHODS AND RESULTS: This study finds that KMP (1, 10 µM) increases the migration and differentiation of C2C12 myoblasts in vitro. Studying the possible mechanism underlying its effect on migration, the study finds that KMP activates Integrin Subunit Beta 1 (ITGB1) in C2C12 myoblasts, increasing p-FAK (Tyr398) and its downstream cell division cycle 42 (CDC42), a protein previously associated with cell migration. Regarding differentiation, KMP upregulates the expression of myosin heavy chain (MHC) and activates IGF1/AKT/mTOR/P70S6K. Interestingly, pretreatment with an AKT inhibitor (LY294002) and siRNA knockdown of IGF1R leads to a decrease in cell differentiation, suggesting that IGF1/AKT activation is required for KMP to induce C2C12 myoblast differentiation. CONCLUSION: Together, the findings suggest that KMP enhances the migration and differentiation of C2C12 myoblasts through the ITG1B/FAK/paxillin and IGF1R/AKT/mTOR pathways. Thus, KMP supplementation might potentially be used to prevent or delay age-related loss of muscle mass and help maintain muscle health.
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Diferenciación Celular , Movimiento Celular , Integrina beta1 , Quempferoles , Mioblastos , Paxillin , Proteínas Proto-Oncogénicas c-akt , Receptor IGF Tipo 1 , Transducción de Señal , Serina-Treonina Quinasas TOR , Animales , Quempferoles/farmacología , Serina-Treonina Quinasas TOR/metabolismo , Ratones , Proteínas Proto-Oncogénicas c-akt/metabolismo , Diferenciación Celular/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Mioblastos/efectos de los fármacos , Mioblastos/metabolismo , Integrina beta1/metabolismo , Paxillin/metabolismo , Línea Celular , Receptor IGF Tipo 1/metabolismo , Receptor IGF Tipo 1/genética , Quinasa 1 de Adhesión Focal/metabolismo , Quinasa 1 de Adhesión Focal/genéticaRESUMEN
An integrated medication management (IMM) model was implemented in a medical center ward to improve the delivery of clinical pharmaceutical services (CPSs). This model incorporated a ward-based clinical pharmacist who performed medication reconciliation and medication reviews. It was perceived to promote interprofessional collaboration between pharmacists and non-pharmacist healthcare professionals (NPHPs, including attending physicians, nurse practitioners, and registered nurses). This study aimed to evaluate the effects of the IMM on NPHPs' intentions to collaborate with pharmacists and understand the mechanism of the impact of the IMM on interprofessional collaboration. A sequential explanatory mixed methods design was employed in the study. Initially, a questionnaire was administered to assess the effects of the IMM on NPHPs' intentions to collaborate with pharmacists. The NPHPs' experiences with the IMM were then documented using semi-structured interviews with inductive thematic analysis. Fifty-eight NPHPs completed the questionnaire, and NPHPs from the intervention ward reported a higher intention to discuss patient-related medication issues with pharmacists, indicating collaboration. Eleven NPHPs were interviewed, and they stated having better working relationships with pharmacists, experiencing more effective CPSs, and noting improved communication with pharmacists. The integration of quantitative and qualitative findings demonstrates that the critical mechanism of the IMM in promoting collaborative relationships is to integrate pharmacists into medical practice, which familiarizes NPHPs with pharmacists' roles, improves communication, and enables pharmacists to identify NPHPs' needs. To summarize, allowing ward-based pharmacists to engage in medical teams on a regular basis appears vital for improving interprofessional teamwork. Furthermore, stakeholders aiming to promote CPS in their institutions should consider the needs and communication channels among NPHPs.
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Relaciones Interprofesionales , Administración del Tratamiento Farmacológico , Humanos , Actitud del Personal de Salud , Hospitales , FarmacéuticosRESUMEN
Aging and muscle disorders frequently cause a decrease in myoblast migration and differentiation, leading to losses in skeletal muscle function and regeneration. Several studies have reported that natural flavonoids can stimulate muscle development. Quercetin, one such flavonoid found in many vegetables and fruits, has been used to promote muscle development. In this study, we investigated the effect of quercetin on migration and differentiation, two processes critical to muscle regeneration. We found that quercetin induced the migration and differentiation of mouse C2C12 cells. These results indicated quercetin could induce myogenic differentiation at the early stage through activated p-IGF-1R. The molecular mechanisms of quercetin include the promotion of myogenic differentiation via activated transcription factors STAT3 and the AKT signaling pathway. In addition, we demonstrated that AKT activation is required for quercetin induction of myogenic differentiation to occur. In addition, quercetin was found to promote myoblast migration by regulating the ITGB1 signaling pathway and activating phosphorylation of FAK and paxillin. In conclusion, quercetin can potentially be used to induce migration and differentiation and thus improve muscle regeneration.
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Proteínas Proto-Oncogénicas c-akt , Quercetina , Animales , Diferenciación Celular , Línea Celular , Ratones , Desarrollo de Músculos/fisiología , Músculo Esquelético/metabolismo , Paxillin/metabolismo , Paxillin/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Quercetina/metabolismo , Quercetina/farmacologíaRESUMEN
BACKGROUND/AIM: Chlorogenic acid (CGA) is a polyphenol compound found in a variety of foods, including coffee, tea, cherries, and apples. It has been found by a number of studies to affect the viability of human cancer cells. No study has investigated its effect on esophageal squamous cell carcinoma (ESCC) metastasis or the molecular mechanism underlying its effect on this disease. MATERIALS AND METHODS: We first used the Taiwanese ESCC cell line CE81T/VGH to create CE81T-M4 cells. Treatment of higher motility cells with chlorogenic acid for 24 h led to inhibition of cell migration and invasion as shown by scratch migration and transwell assays. RESULTS: Western blotting showed that chlorogenic acid halted the activation of EGFR/p-Akt/Snail pathway and suppressed the expression of MMP-2 and MMP-9. Knockdown of either EGFR or Akt inhibited Snail, MMP2, and MMP9 activity as well as cell migration and invasion. CONCLUSION: Chlorogenic acid inhibited cancer cell motility via the EGFR/p-Akt/Snail pathway and could potentially be used to develop an antimetastatic agent for ESCC in the future.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Línea Celular Tumoral , Ácido Clorogénico/farmacología , Receptores ErbB/metabolismo , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/patología , Humanos , Invasividad Neoplásica/patología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de SeñalRESUMEN
BACKGROUND: Medication errors (MEs) are harmful to patients during hospitalization, especially elderly patients. To reduce MEs, an integrated medication management (IMM) model was developed in a 2500-bed medical center, allowing a clinical pharmacist to participate in the daily ward round and perform medication reconciliation and medication reviews. This study aimed to evaluate the impact of the IMM model on MEs and medication utilization using a quasi-experimental design. METHODS: We conducted an interrupted time-series study using the aggregated data of monthly admissions from two wards of a medical center, where one ward served as the intervention and the other served as the external control. The pre- and post-intervention phases comprised of 40 and 12 monthly observational units, respectively. The primary outcome was the mean number of ME reports, which were further investigated for different ME types. The mean number of daily inpatient prescriptions, mean number of daily self-prepared medications, and median daily medication costs were measured. All outcomes were measured per admission episode. Segmented regression was used to evaluate the level and slope changes in the outcomes after IMM model implementation, and subgroup analyses were performed to examine the effects on different groups. RESULTS: After IMM model implementation, the mean number of ME reports increased (level change: 1.02, 95% confidence interval [CI]: 0.68 to 1.35, P < 0.001). The number of reports has shown a dramatic increase in omissions or medication discrepancies, inappropriate drug choices, and inappropriate routes or formulations. Furthermore, the mean number of daily inpatient prescriptions was reduced for patients aged ≥75 years (level change: -1.78, 95% CI: -3.06 to -0.50, P = 0.009). No significant level or slope change was observed in the control ward during the post-intervention phase. CONCLUSIONS: The IMM model improved patient safety and optimized medication utilization by increasing the reporting of MEs and decreasing the number of medications used.
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Administración del Tratamiento Farmacológico , Admisión del Paciente , Anciano , Humanos , Análisis de Series de Tiempo Interrumpido , Errores de Medicación/prevención & control , Conciliación de Medicamentos , FarmacéuticosRESUMEN
This study aims to identify new upregulated genes related to secretory or membranous proteins to help detect esophageal squamous cell carcinoma (ESCC). First, we performed microarray-based screening of esophageal tumors from both N-nitrosomethylbenzylamine- and arecoline-induced F344 rats and seventeen human ESCC specimens. Candidate genes were validated by quantitative PCR (qPCR) and immunohistochemical (IHC) staining of ESCC tissues. Among the paired cancer and adjacent normal tissues from 14 ESCC patients, 10 pairs (71.4%) had overexpression of ATP1A1 (ATPase Na+/K+ transporting alpha 1 polypeptide) by qPCR (P = 0.0052). ATP1A1 protein expression was re-confirmed by tissue arrays in 243 ESCC tissues and 126 adjacent normal tissues and by ELISA in 78 serum specimens of ESCC patients. ATP1A1 was 12.3 times (adjusted odds ratio=12.3, 95% CI = 7.2-21.0) more likely to be overexpressed in cancer tissues than in normal tissues. ATP1A1 expression was also correlated to tumor stage. Patients with higher serum ATP1A1 levels had a 2.9-fold (95% CI = 1.1-7.4) risk of late-stage disease (stages III-IV vs. I-II). Downregulation of ATP1A1 expression inhibited the migration and invasion ability of ESCC cell lines in vitro. We concluded that the overexpression of ATP1A1 is strongly associated with the presence and severity of ESCC.
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Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Neoplasias Esofágicas/diagnóstico , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Animales , Arecolina/toxicidad , Biomarcadores de Tumor/genética , Carcinogénesis , Carcinoma de Células Escamosas/inducido químicamente , Línea Celular Tumoral , Dimetilnitrosamina/análogos & derivados , Dimetilnitrosamina/toxicidad , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Análisis por Micromatrices , Ratas , ATPasa Intercambiadora de Sodio-Potasio/genética , Regulación hacia ArribaRESUMEN
This study aimed to identify noninvasive protein markers capable of detecting the presence and prognosis of esophageal squamous-cell carcinoma (ESCC). Analyzing microarray expression data collected from 17-pair ESCC specimens, we identified one protein, matrix metalloproteinase-1 (MMP1), as a possibly useful marker. Plasma MMP1 was then measured by enzyme-linked immunosorbent assay (ELISA) in 210 ESCC patients and 197 healthy controls. ESCC patients had higher mean levels of MMP1 than controls (8.7 ± 7.5 vs. 6.7 ± 4.9 ng/mL, p < 0.0001). Using the highest quartile level (9.67 ng/mL) as cut-off, we found a 9.0-fold risk of ESCC in those with higher plasma MMP1 after adjusting for covariates (95% confidence interval = 2.2, 36.0). Heavy smokers and heavy drinkers with higher plasma MMP1 had 61.4- and 31.0 times the risk, respectively, than non-users with lower MMP1. In the survival analysis, compared to those with MMP1 ≤ 9.67 ng/mL, ESCC patients with MMP1 > 9.67 ng/mL had a 48% increase in the risk of ESCC death (adjusted hazard ratio = 1.48; 95% CI = 1.04-2.10). In conclusion, plasma MMP1 may serve as a noninvasive marker of detecting the presence and predicting the survival of ESCC.
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Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patología , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/patología , Metaloproteinasa 1 de la Matriz/sangre , Plasma/química , Adulto , Anciano , Carcinoma de Células Escamosas/mortalidad , Ensayo de Inmunoadsorción Enzimática , Neoplasias Esofágicas/mortalidad , Carcinoma de Células Escamosas de Esófago , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Análisis de SupervivenciaRESUMEN
Background. To achieve the weight gain of preterm infants who are appropriate for gestational age without adverse effect, there should be no interruption in delivery of nutrients from time of birth. Methods. Twenty-eight very low birth weight infants were eligible for the study. Those administered conventional nutrition (amino acids 2 g/kg/day started on third day of life) were classified as the conventional support (CVS) group, and those administered aggressive early nutrition (amino acid 2 g/kg/day started on first day of life) were classified as the aggressive support (AGS) group. Results. The days babies took to reach the weight of 2000 g in the AGS group was significantly shorter than for babies in the CVS group, and babies in the AGS group showed better tolerance to enteral nutrition and had shortened neonatal intensive care unit days. Conclusion. The results demonstrated that aggressive early nutrition showed better tolerance to enteral nutrition, higher total calories, and shortened the stay in the neonatal intensive care unit.
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Water-soluble polysaccharides extracted from mushrooms have been found to have some physiological effects. In this study, exopolysaccharides (EPSs) were extracted by alcohol precipitation from cultivated broth of the mushroom Clitocybe maxima. EPSs with molecular weights of 10(4) and 10(5) Da were obtained by ultrafiltration; they are referred to as EPA and EPB, respectively. The major components of these EPSs were glucose, galactose, mannose, rhamnose, and arabinose. ICR mice with artificially induced metastatic pulmonary tumors were fed a daily diet containing EPA or EPB at doses of 8, 20, or 50 mg/kg. Results showed that the proliferation of pulmonary sarcoma lesions was lower in the groups fed EPS. In addition, the numbers of total T cells, CD4+ cells, CD8+ cells, and macrophages significantly increased in EPS-fed mice compared with the negative control group. The antitumor and immunomodulating effects observed in the EPB-fed groups were higher than those of EPA-fed groups. These results demonstrate the ability of EPSs of C. maxima to inhibit tumor cells while enhancing immune response.
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Antineoplásicos/uso terapéutico , Basidiomycota/química , Productos Biológicos/uso terapéutico , Factores Inmunológicos/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Polisacáridos/uso terapéutico , Sarcoma 180/tratamiento farmacológico , Animales , Antineoplásicos/farmacología , Productos Biológicos/farmacología , Linfocitos T CD4-Positivos/metabolismo , Factores Inmunológicos/farmacología , Inmunomodulación , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Masculino , Ratones Endogámicos ICR , Peso Molecular , Polisacáridos/farmacología , Sarcoma 180/inmunologíaRESUMEN
DMPC and DSPC liposomes were prepared via thin film hydration method followed by sonication. Propranolol solution was incorporated into liposomes at hydration stage. TEM images showed the sizes of DSPC and DMPC were around 88 and 137 nm, respectively. The highest encapsulation ratio of propranolol was approximately 70% using DSPC/CHO/OCT liposomes, which release the drug over 60% in 24 h and reached 100% in 48 h. Both propranolol (10â»8-10â»6 M) and DSCP liposomes-encapsulated propranolol showed over 1.5-fold increases in the proliferation of human osteoblastic cells hFOB1.19 while differentiation of the cells was approximately doubled by plain and liposomal propranolol, indicating that the stimulatory effects of liposomal propranolol are similar with those of propranolol on human osteoblastic hFOB1.19 cells. The phosphatidylcholine liposomes-encapsulated propranolol prepared in this study potentially possesses anabolic effects in vivo and is also a promising anti-osteoporotic agent in future.
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Liposomas/química , Osteoblastos/citología , Osteoblastos/fisiología , Osteogénesis/fisiología , Fosfatidilcolinas/administración & dosificación , Propranolol/administración & dosificación , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/fisiología , Línea Celular , Proliferación Celular/efectos de los fármacos , Proliferación Celular/fisiología , Difusión , Humanos , Ensayo de Materiales , Osteoblastos/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Fosfatidilcolinas/química , Propranolol/químicaRESUMEN
BACKGROUND: Focal hypermethylation in promoter regions of tumor suppressor genes against the background of global hypomethylation is a landmark of carcinogenesis. This study aimed to investigate the methylation status of retinoic acid receptor beta2 (RARß2) and long interspersed nuclear elements (LINE-1) in different stages of esophageal squamous cell carcinoma (ESCC). METHOD: The tumor and adjacent normal esophageal tissues from 125 male ESCC patients who underwent primary surgery were analyzed for the methylation status of RARß2 promoter and LINE-1 through methylation-specific polymerase chain reaction and pyrosequencing. RESULTS: RARß2 hypermethylation was detected in 20% of the tumor samples, but not in the normal counterparts. The methylation frequency of LINE-1 was significantly lower in the tumor than in the normal parts (median: 67.7% vs. 80%, P < 0.0005). Ninety-eight patients (78.4%) had both RARß2 hypermethylation and LINE-1 hypomethylation or either one. There was a trend toward higher risk of advanced T stage (P for trend = 0.05) or lymph node metastasis (P for trend = 0.02) when more adverse gene methylation profiles were present. CONCLUSION: Methylation status of RARß2 and LINE-1 was related to the development and possibly the severity of ESCC.
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Carcinoma de Células Escamosas/genética , Metilación de ADN , Neoplasias Esofágicas/genética , Receptores de Ácido Retinoico/genética , Biomarcadores de Tumor/genética , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Quimioradioterapia , Quimioterapia Adyuvante , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/terapia , Humanos , Elementos de Nucleótido Esparcido Largo/genética , Metástasis Linfática , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Radioterapia AdyuvanteRESUMEN
Sinulariolide is an active compound isolated from the cultured soft coral Sinularia flexibilis. In this study, we investigated the effects of sinulariolide on A375 melanoma cell growth and protein expression. Sinulariolide suppressed the proliferation and migration of melanoma cells in a concentration-dependent manner and was found to induce both early and late apoptosis by flow cytometric analysis. Comparative proteomic analysis was conducted to investigate the effects of sinulariolide at the molecular level by comparison between the protein profiles of melanoma cells treated with sinulariolide and those without treatment. Two-dimensional gel electrophoresis (2-DE) master maps of control and treated A375 cells were generated by analysis with PDQuest software. Comparison between these maps showed up- and downregulation of 21 proteins, seven of which were upregulated and 14 were downregulated. The proteomics studies described here identify some proteins that are involved in mitochondrial dysfunction and apoptosis-associated proteins, including heat shock protein 60, heat shock protein beta-1, ubiquinol cytochrome c reductase complex core protein 1, isocitrate dehydrogenase (NAD) subunit alpha (down-regulated), and prohibitin (up-regulated), in A375 melanoma cells exposed to sinulariolide. Sinulariolide-induced apoptosis is relevant to mitochondrial-mediated apoptosis via caspase-dependent pathways, elucidated by the loss of mitochondrial membrane potential, release of cytochrome c, and activation of Bax, Bad and caspase-3/-9, as well as suppression of p-Bad, Bcl-xL and Bcl-2. Taken together, our results show that sinulariolide-induced apoptosis might be related to activation of the caspase cascade and mitochondria dysfunction pathways. Our results suggest that sinulariolide merits further evaluation as a chemotherapeutic agent for human melanoma.
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Apoptosis/efectos de los fármacos , Apoptosis/genética , Caspasas/genética , Diterpenos/farmacología , Melanoma/tratamiento farmacológico , Mitocondrias/genética , Proteoma/genética , Animales , Antozoos/metabolismo , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Caspasas/metabolismo , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Movimiento Celular/genética , Proliferación Celular/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Regulación hacia Abajo/genética , Humanos , Melanoma/genética , Melanoma/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Potencial de la Membrana Mitocondrial/genética , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Proteoma/metabolismo , Proteómica/métodos , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , Regulación hacia Arriba/efectos de los fármacos , Regulación hacia Arriba/genéticaRESUMEN
With an aim to explore the productivity and quality of the fruiting body of culinary-medicinal golden oyster mushroom Pleurotus citrinopileatus, the carbon dioxide (CO2) concentration of the ambient atmosphere was adjusted and a light-emitting diode panel was used to illuminate the colonized mycelium at different wavelengths. Biological efficiency and yield were higher at CO2 levels of 0.05 and 0.1% than other tested CO2 levels, and the mature fruiting body showed the highest yellow value at a CO2 level of 0.1% (of all tested CO2 levels). The highest biological efficiency and yield was obtained at the 720-nm wavelength. The ergosterol content of the pileus of the fruiting body was higher than that of the stipe in any flush time at a 720-nm wavelength of light and a CO2 concentration of 0.1%. The decreased percentages of cellulose and lignin at the appearance of primordia were larger than those of mycelial growth duration. The fruiting quality of P. citrinopileatus might thus be enhanced by 720-nm illumination and an atmosphere with a CO2 concentration of 0.1 to 0.15%.
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Atmósfera , Luz , Pleurotus/clasificación , Pleurotus/fisiologíaRESUMEN
Esophageal squamous cell cancer (ESCC) is one of the most common fatal human cancers. The identification of biomarkers for early detection could be a promising strategy to decrease mortality. Previous studies utilized microarray techniques to identify more than one hundred genes; however, it is desirable to identify a small set of biomarkers for clinical use. This study proposes a sequential forward feature selection algorithm to design decision tree models for discriminating ESCC from normal tissues. Two potential biomarkers of RUVBL1 and CNIH were identified and validated based on two public available microarray datasets. To test the discrimination ability of the two biomarkers, 17 pairs of expression profiles of ESCC and normal tissues from Taiwanese male patients were measured by using microarray techniques. The classification accuracies of the two biomarkers in all three datasets were higher than 90%. Interpretable decision tree models were constructed to analyze expression patterns of the two biomarkers. RUVBL1 was consistently overexpressed in all three datasets, although we found inconsistent CNIH expression possibly affected by the diverse major risk factors for ESCC across different areas.
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Algoritmos , Biomarcadores de Tumor/análisis , Carcinoma de Células Escamosas/química , Proteínas Portadoras/análisis , ADN Helicasas/análisis , Árboles de Decisión , Proteínas del Huevo/análisis , Neoplasias Esofágicas/química , Perfilación de la Expresión Génica , Proteínas de la Membrana/análisis , Análisis de Secuencia por Matrices de Oligonucleótidos , ATPasas Asociadas con Actividades Celulares Diversas , Biomarcadores de Tumor/biosíntesis , Biomarcadores de Tumor/genética , Carcinoma de Células Escamosas/genética , Proteínas Portadoras/biosíntesis , Proteínas Portadoras/genética , ADN Helicasas/biosíntesis , ADN Helicasas/genética , ADN Complementario/genética , Bases de Datos Genéticas , Detección Precoz del Cáncer , Proteínas del Huevo/biosíntesis , Proteínas del Huevo/genética , Neoplasias Esofágicas/genética , Humanos , Masculino , Proteínas de la Membrana/biosíntesis , Proteínas de la Membrana/genética , Valor Predictivo de las Pruebas , ARN Mensajero/genética , ARN Neoplásico/genética , Sensibilidad y EspecificidadRESUMEN
Sinulariolide, an isolated compound from the soft coral Sinularia flexibilis, possesses the anti-proliferative, anti-migratory and apoptosis-inducing activities against the TSGH bladder carcinoma cell. The anti-tumor effects of sinulariolide were determined by 3-(4,5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, cell migration assay and flow cytometry, respectively. Sinulariolide inhibited the growth and migration of bladder carcinoma cells in a dose-dependent manner, as well as induced both early and late apoptosis as determined by the flow cytometer. Also, the sinulariolide-induced apoptosis is related to the mitochondrial-mediated apoptosis via caspase-dependent pathways, elucidated by the loss of mitochondrial membrane potential, release of cytochrome C, activation of caspase-3/-9, Bax and Bad, as well as suppression of Bcl-2/Bcl-xL/Mcl-1. Detection of the PARP-1 cleaved product suggested the partial involvement of caspase-independent pathways. Moreover, inhibition of p38MAPK activity leads to the rescue of the cell cytotoxicity of sinulariolide-treated TSGH cells, indicating that the p38MAPK pathway is also involved in the sinulariolide-induced cell apoptosis. Altogether, these results suggest that sinulariolide induces apoptosis against bladder cancer cells through mitochondrial-related and p38MAPK pathways.
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Antozoos/química , Antineoplásicos/farmacología , Diterpenos/farmacología , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/aislamiento & purificación , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Citocromos c/metabolismo , Diterpenos/administración & dosificación , Diterpenos/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Citometría de Flujo , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Factores de Tiempo , Neoplasias de la Vejiga Urinaria/patología , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
This study aims to explore whether certain occupations were associated with the risk of esophageal squamous cell carcinoma (ESCC) in Taiwan. In a hospital-based case-control study, we collected 326 newly diagnosed ESCC patients and 386 age-matched controls (the ratio of case patients: controls = 1:1-2). All respondents completed a questionnaire, including 33 occupations in which environments potential exposure to cancer-related hazards are present. Workers with dust and metal exposure were categorized into Groups A and B, respectively. Relative risks for ESCC were estimated by odds ratios adjusting for covariates (AOR). Compared with the controls, farmer/gardener (AOR = 2.08, 95% CI = 1.02-4.24) and workers in Group A (AOR = 2.80, 95% CI = 1.21-6.47) had significantly higher risk for developing ESCC. A tendency of increased risk was also found in workers in group B (OR = 5.72 95% CI = 2.33-14.03), but such association was not significant after adjusting for other covariates (AOR = 1.57, 95% CI = 0.54-6.61). Our results suggested that farmer/gardener and workers with exposure to dust had a significant excess risk of ESCC. This study added further evidence to the current knowledge that occupational hazards are important in the development of ESCC.
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Neoplasias Esofágicas/epidemiología , Enfermedades Profesionales/epidemiología , Anciano , Agricultura , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/etnología , Estudios de Casos y Controles , Polvo , Neoplasias Esofágicas/etnología , Humanos , Masculino , Metales , Persona de Mediana Edad , Enfermedades Profesionales/etnología , Exposición Profesional/efectos adversos , Oportunidad Relativa , Factores de Riesgo , Encuestas y Cuestionarios , Taiwán/epidemiologíaRESUMEN
BACKGROUND: Once diagnosed, esophageal cancer has a very low overall 5-year survival rate. This study investigates the mechanisms behind the invasiveness and severity of esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: Transwell invasion chamber was used to subdivide one Taiwanese ESCC cell line, CE81T/VGH, into sublines (CE81T-0, CE81T-1, CE81T-2, CE81T-3, and CE81T-4) in four rounds of assays; the most invasive were identified, and various factors related to their invasiveness measured. RESULTS: CE81T-1, CE81T-2, CE81T-3 and CE81T-4 sublines were significantly more invasive than the parental cells (CE81T/VGH) and CE81T-0 subline. CE81T-1 and CE81T-4, the sublines we chose to study further, had significantly greater colony-forming ability (3.5- to 2.7-fold) and wound migrating activity (1.95- to 2.6-fold) than the parental cells in vitro (p<0.01). They also displayed greater tumorigenesis in immunodeficient BALB/c Foxlnn mice than the parental cells. We found an inverse correlation between expression of tissue inhibitor of metalloproteinase-2 and invasive ability, and a significant positive correlation between expressions of matrix metalloproteinase-1, vimentin, and p-Src (pY416) in these cell lines and their invasiveness (all p<0.05). CONCLUSION: The subline model may be used to study the molecular and genetic mechanisms underlying the invasion and metastasis of ESCC.
Asunto(s)
Carcinoma de Células Escamosas/patología , Neoplasias Esofágicas/patología , Animales , Western Blotting , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Procesos de Crecimiento Celular/fisiología , Línea Celular Tumoral , Movimiento Celular/fisiología , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Citometría de Flujo , Humanos , Masculino , Metaloproteinasa 1 de la Matriz/biosíntesis , Metaloproteinasa 1 de la Matriz/genética , Metaloproteinasa 2 de la Matriz/biosíntesis , Metaloproteinasa 2 de la Matriz/genética , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Invasividad Neoplásica , Metástasis de la Neoplasia , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Inhibidor Tisular de Metaloproteinasa-2/biosíntesis , Vimentina/biosíntesis , Vimentina/genéticaRESUMEN
Using a microarray technique, we found decorin to be underexpressed, but osteopontin (OPN) to be overexpressed, in esophageal squamous cell carcinoma (ESCC). This study aims to examine whether plasma decorin and OPN plus personal substances use (tobacco, alcohol and areca) can serve as suitable clinical markers to predict the presence of ESCC. In total, 570 archived plasma specimens (275 patients and 295 controls) were collected from 2 medical centers in Taiwan between 2000 and 2008. Decorin and OPN protein levels were measured by ELISA. Means and standard deviation of plasma decorin were 5.6 + or - 3.6 ng/ml in case patients, which were significantly lower than those in controls (7.8 + or - 3.1, p < 0.0001). Plasma OPN levels in case patients were not significantly different from controls (p = 0.33). When compared to subjects with the lowest quartile of plasma decorin, those with the highest quartile one had a significantly lower risk to have ESCC (Adjusted OR = 0.03, p < 0.001). Receiver operator characteristic (ROC) analysis was performed for the combination of plasma decorin and 3 substances use (smoke, alcohol and areca) for the patients compared with the controls. The area under the curve was 88.6% and the optimal cut-point of ROC curve (any 3 factors) had 73.5% sensitivity and 90.2% specificity with approximately 82% of corrected classification. Plasma decorin, but not OPN, is a potential clinical marker for the detection of ESCC. When plasma decorin plus the use of the 3 substances are combined, this factor cluster could be used to detect the presence of ESCC.
Asunto(s)
Biomarcadores de Tumor/sangre , Carcinoma de Células Escamosas/diagnóstico , Neoplasias Esofágicas/diagnóstico , Proteínas de la Matriz Extracelular/sangre , Proteoglicanos/sangre , Consumo de Bebidas Alcohólicas , Estudios de Casos y Controles , Decorina , Femenino , Humanos , Masculino , Persona de Mediana Edad , Osteopontina/sangre , Pronóstico , FumarRESUMEN
OBJECTIVES: To identify a better set of DNA methylation markers to detect superficial, low grade cancer cell in urine sediment for improving cancer treatment, morbidity, and mortality. MATERIALS AND METHODS: Methylation-specific PCR (MSP) assay was used to detect promoter hypermethylation in 4 genes (E-cadherin, p16, p14, and RASSF1A) to identify reliable biomarkers for bladder cancer diagnosis in primary tumor DNA and urine sediment DNA from 57 bladder cancer patients. Urine DNA was compared with 20 healthy controls. RESULTS: Fifty-one (90%) tumor DNA and 47 urine DNA (83%) samples from bladder cancer patients revealed hypermethylation in at least 1 of the 4 analyzed genes, whereas all urine samples from normal controls were negative. The sensitivity of MSP assay for detecting E-cadherin, p16, p14 and RASSF1A in tumor cells in voided urine was 35%, 35%, 33%, and 65%, respectively. Diagnostic sensitivity was 75% for combining RASSF1A and p14, and 83% for RASSF1A, p14 and E-cadherin. Urine cytology, however, detect only 13 (28%) cases of cancer or suspicious cancer. For detecting superficial and invasive bladder tumor, urine cytology revealed a sensitivity of 23% (6/26) and 35% (7/20), respectively. In contrast, MSP detected hypermethylation in the urine of 80% (37/46) bladder cancer patients. Moreover, hypermethylation analysis of E-cadherin, p14 or RASSF1A genes in urine sediment DNA detected in 85% (22/26) of superficial, 85% (11/13) of low grade, 75% (15/20) of invasive and 79% (26/33) of high grade bladder cancers. Importantly, hypermethylation was detected in the urine DNA of 90% (18/20) superficial tumors with negative or atypia cytology. CONCLUSIONS: Hypermethylation of E-cadherin, p14 or RASSF1A in urine sediment DNA is a potential biomarker for detecting superficial, low grade cancer. Besides, hypermethylation of these 3 genes is a valuable adjunct diagnostic marker to urine cytology, which can enhance the diagnostic accuracy and follow-up treatment of bladder cancer patients.