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Bridge inspection and monitoring are usually used to evaluate the status and integrity of bridge structures to ensure their safety and reliability. Computer vision (CV)-based methods have the advantages of being low cost, simple to operate, remote, and non-contact, and have been widely used in bridge inspection and monitoring in recent years. Therefore, this paper reviews three significant aspects of CV-based methods, including surface defect detection, vibration measurement, and vehicle parameter identification. Firstly, the general procedure for CV-based surface defect detection is introduced, and its application for the detection of cracks, concrete spalling, steel corrosion, and multi-defects is reviewed, followed by the robot platforms for surface defect detection. Secondly, the basic principle of CV-based vibration measurement is introduced, followed by the application of displacement measurement, modal identification, and damage identification. Finally, the CV-based vehicle parameter identification methods are introduced and their application for the identification of temporal and spatial parameters, weight parameters, and multi-parameters are summarized. This comprehensive literature review aims to provide guidance for selecting appropriate CV-based methods for bridge inspection and monitoring.
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Residual strength of corroded textile-reinforced concrete (TRC) is evaluated using the deep learning-based method, whose feasibility is demonstrated by experiment. Compared to the traditional method, the proposed method does not need to know the climatic conditions in which the TRC exists. Firstly, the information about the faster region-based convolutional neural networks (Faster R-CNN) is described briefly, and then procedures to prepare datasets are introduced. Twenty TRC specimens were fabricated and divided into five groups that were treated to five different corrosion degrees corresponding to five different residual strengths. Five groups of images of microstructure features of these TRC specimens with five different residual strengths were obtained with portable digital microscopes in various circumstances. With the obtained images, datasets required to train, validate, and test the Faster R-CNN were prepared. To enhance the precision of residual strength evaluation, parameter analysis was conducted for the adopted model. Under the best combination of considered parameters, the mean average precision for the residual strength evaluation of the five groups of the TRC is 98.98%. The feasibility of the trained model was finally verified with new images and the procedures to apply the presented method were summarized. The paper provides new insight into evaluating the residual strength of structural materials, which would be helpful for safety evaluation of engineering structures.
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The first generation of immune checkpoint inhibitors (ICIs) including anti-CTLA-4 and anti-PD-1/anti-PD-L1 has achieved profound and great success. Till 2019 Q1, there are nine ICIs landing the oncology market: Ipilimumab (anti-CTLA-4, Bristol-Myers Squibb), Nivolumab (anti-PD-1, Bristol-Myers Squibb), Pembrolizumab (anti-PD-1, Merck), Atezolizumab (anti-PD-L1, Roche/Genentech), Durvalumab (anti-PD-L1, Astra Zeneca), Tremelimumab (anti-CTLA-4, Astra Zeneca), Cemiplimab (anti-PD-1, Sanofi/Regeneron), Toripalimab (anti-PD-1, Junshi), and Sintilimab (anti-PD-1, Innovent), which have covered the majority of hematologic and solid malignancies' indication. Beyond the considerable benefits for the patients, frustrated boundary still exists: limited response rate in monotherapy in late-stage population, poor effectiveness in neoplasms with immune desert and immune excluded types, and immune-related toxicities, some are life-threatened and with higher incidence in I-O combination regiment. Moreover, clinicians observed some cases switching to progression after achieving partial or complete response, indicating treatment failure or drug resistance. So people begin looking for the next generation of immune checkpoint members.
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Puntos de Control del Ciclo Celular/efectos de los fármacos , Puntos de Control del Ciclo Celular/inmunología , Descubrimiento de Drogas , Neoplasias/tratamiento farmacológico , Neoplasias/inmunología , Receptores Inmunológicos/antagonistas & inhibidores , Humanos , Neoplasias/patologíaRESUMEN
We present a facile strategy to prepare the molecularly imprinted polymers layer on the surface of Fe3 O4 nanoparticles with core-shell structure via sol-gel condensation for recognition and enrichment of triclosan. The Fe3 O4 nanoparticles were first synthesized by a solvothermal method. Then, template triclosan was self-assembled with the functional monomer 3-aminopropyltriethoxysilane on the silica-coated Fe3 O4 nanoparticles in the presence of ethanol and water. Finally, the molecularly imprinted polymers were formed on the surface of silica-coated Fe3 O4 nanoparticles to obtain the product. The morphology, magnetic susceptibility, adsorption, and recognition property of magnetic molecularly imprinted polymers were characterized using transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray diffractometry, vibrating sample magnetometry, and re-binding experiments. The magnetic molecularly imprinted polymers showed binding sites with good accessibility, fast adsorption rate, and high adsorption capacity (218.34 µg/g) to triclosan. The selectivity of magnetic molecularly imprinted polymers was evaluated by the rebinding capability of triclosan and two other structural analogues (phenol and p-chlorophenol) in a mixed solution and good selectivity with an imprinting factor of 2.46 was obtained. The application of triclosan removal in environmental samples was demonstrated.
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OBJECTIVE: The purpose of this study was to determine if transcutaneous electrical nerve stimulation (TENS) improves sleep in chronic low back pain (CLBP). BACKGROUND: There is uncertainty over the effectiveness of TENS in CLBP. In most studies, pain intensity has been the primary outcome measure. Although sleep abnormalities are common in CLBP, sleep outcomes have not been evaluated in most studies of TENS effectiveness. Subjective and objective sleep measures are often inconsistent in CLBP, suggesting that perception of sleep and actual sleep may differ. METHODS: This retrospective cohort study evaluated TENS for CLBP over 10 weeks. The source database included demographics, pain characteristics, pain intensity and interference on an 11-point numerical rating scale, adherence and actigraphic sleep data from real-world TENS users. Key inclusion criteria were CLBP with self-reported history of back injury and baseline pain interference with sleep ≥4. Study participants were stratified into improved and unimproved groups based on changes in pain interference with sleep (improved ≥1-point decrease). Actigraphic sleep metrics were compared between the two groups for weeks 1-2 and weeks 9-10. RESULTS: The inclusion criteria were met by 554 TENS users. There were 282 (50.9%) participants in the improved group and 272 (49.1%) in the unimproved group. The two groups had similar baseline characteristics and high TENS adherence. At the weeks 1-2 assessment, there were no differences among actigraphic sleep. At the weeks 9-10 assessment, there was a difference in total sleep time, with the improved group sleeping 29 minutes longer. In addition, the periodic leg movement (PLM) index was lower in the improved group. CONCLUSION: Regular TENS improved self-reported and objective sleep measures in individuals with CLBP. When compared to the unimproved group, the improved group had longer total sleep time and fewer PLMs. Sleep may be an important outcome for TENS effectiveness in CLBP.
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The abnormal expression of microRNAs (miRNAs) in colorectal cancer (CRC) progression has been widely investigated. It was reported that the same hairpin RNA structure could generate mature products from each strand, termed 5p and 3p, which binds different target mRNAs. Here, we explored the expression, functions, and mechanisms of miR-514b-3p and miR-514b-5p in CRC cells and tissues. We found that miR-514b-3p was significantly down-regulated in CRC samples, and the ratio of miR-514b-3p/miR-514b-5p increased from advanced CRC, early CRC to matched normal colorectal tissues. Follow-up functional experiments illustrated that miR-514b-3p and miR-514b-5p had distinct effects through interacting with different target genes: MiR-514b-3p reduced CRC cell migration, invasion and drug resistance through increasing epithelial marker and decreasing mesenchymal marker expressions, conversely, miR-514b-5p exerted its pro-metastatic properties in CRC by promoting EMT progression. MiR-514b-3p overexpressing CRC cells developed tumors more slowly in mice compared with control cells, however, miR-514b-5p accelerated tumor metastasis. Overall, our data indicated that though miR-514b-3p and miR-514b-5p were transcribed from the same RNA hairpin, each microRNA has distinct effect on CRC metastasis.
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Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , MicroARNs/metabolismo , Animales , Secuencia de Bases , Línea Celular Tumoral , Progresión de la Enfermedad , Resistencia a Antineoplásicos , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Ratones Desnudos , MicroARNs/genética , Invasividad Neoplásica , Metástasis de la NeoplasiaRESUMEN
OBJECTIVE: The objective of this study was to assess the effectiveness of fixed-site high-frequency transcutaneous electrical nerve stimulation (FS-TENS) in a real-world chronic pain sample. BACKGROUND: There is a need for nonpharmacological treatment options for chronic pain. FS-TENS improved multisite chronic pain in a previous interventional study. Large observational studies are needed to further characterize its effectiveness. METHODS: This retrospective observational cohort study examined changes in chronic pain measures following 60 days of FS-TENS use. The study data were obtained from FS-TENS users who uploaded their device utilization and clinical data to an online database. The primary outcome measures were changes in pain intensity and pain interference with sleep, activity, and mood on an 11-point numerical rating scale. Dose-response associations were evaluated by stratifying subjects into low (≤30 days), intermediate (31-56 days), and high (≥57 days) utilization subgroups. FS-TENS effectiveness was quantified by baseline to follow-up group differences and a responder analysis (≥30% improvement in pain intensity or ≥2-point improvement in pain interference domains). RESULTS: Utilization and clinical data were collected from 11,900 people using FS-TENS for chronic pain, with 713 device users meeting the inclusion and exclusion criteria. Study subjects were generally older, overweight adults. Subjects reported multisite pain with a mean of 4.8 (standard deviation [SD] 2.5) pain sites. A total of 97.2% of subjects identified low back and/or lower extremity pain, and 72.9% of subjects reported upper body pain. All pain measures exhibited statistically significant group differences from baseline to 60-day follow-up. The largest changes were pain interference with activity (-0.99±2.69 points) and mood (-1.02±2.78 points). A total of 48.7% of subjects exhibited a clinically meaningful reduction in pain interference with activity or mood. This proportion increased to 57.1% for the high utilization subgroup. CONCLUSION: FS-TENS is a practical option for treating multisite chronic pain. The greatest impact is on pain interference with activity and mood. FS-TENS utilization and effectiveness exhibit a dose-response association, suggesting that daily use maximizes pain relief.
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AIM: To investigate the factors influencing the occurrence of gastric varioliform lesions (GVLs) and their possible link with gastric cancer. METHODS: A 1:1 matched case-control study was performed to retrospectively analyze data from 1638 chronic gastritis patients who had undergone gastroscopy at one of two Chinese hospitals between 2009 and 2014. Patients with GVLs (cases) were compared to those without such lesions (controls). Endoscopic and pathological findings were recorded, along with interview information on Helicobacter pylori (H. pylori) infection, medical, drug and family histories, lifestyle and eating habits. The association between each factor and the occurrence of GVLs was estimated, and then multivariate conditional logistic regression was used to evaluate the independent factors. RESULTS: The frequency and severity of glandular atrophy, intestinal metaplasia (IM) and low-grade intraepithelial neoplasia were significantly increased in the GVL group (P < 0.01). Overall analysis showed that H. pylori infection [3.051 (2.157, 4.317), P <0.001], allergic respiratory diseases [3.636 (2.183, 6.055), P < 0.001], work-related stress [2.019 (1.568, 2.600), P < 0.001], irregular meals [2.300 (1.462, 3.619), P < 0.001], high intake of spicy food [1.754 (1.227, 2.507), P = 0.002] and high intake of fresh fruit [0.231 (0.101, 0.529), P = 0.001] were significantly correlated with the occurrence of GVLs (positively, except for the latter). Stratified analyses indicated that pickled food consumption in patients over 50 years old [7.224 (2.360, 22.115), P = 0.001] and excessive smoking in men [2.013 (1.282, 3.163), P = 0.002] were also positively correlated, and that, for antral GVLs, vegetable consumption [0.491 (0.311, 0.776), P = 0.002] was negatively correlated. CONCLUSION: Seven risk factors and two protective factors are determined for GVLs, which were found to be associated with premalignant abnormalities.
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Carcinoma in Situ/etiología , Mucosa Gástrica/patología , Gastritis/etiología , Lesiones Precancerosas/etiología , Neoplasias Gástricas/etiología , Atrofia , Carcinoma in Situ/patología , Distribución de Chi-Cuadrado , China , Enfermedad Crónica , Femenino , Gastritis/patología , Gastroscopía , Humanos , Modelos Logísticos , Masculino , Metaplasia , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Lesiones Precancerosas/patología , Factores Protectores , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la Enfermedad , Neoplasias Gástricas/patologíaRESUMEN
OBJECTIVE: To assess patient satisfaction with outpatient and inpatient care between primary care providers and secondary/tertiary hospitals, and to examine its association with socio-demographic characteristics and type of institution, based on self-reported survey data. DESIGN: Cross-sectional survey. SETTING: Healthcare facilities within Jilin province, China. PARTICIPANTS: In total, 993 outpatients and 925 inpatients aged ≥15 years old were recruited. MAIN OUTCOME MEASURES: Patient satisfaction with the care experience. RESULTS: Patient satisfaction with outpatient and inpatient care was significantly associated with type of healthcare delivery setting in Jilin, China. Seeking outpatient care from community health centers (CHCs) was significantly associated with a higher ratio of patient satisfaction. Patients of county and tertiary hospitals complained about long-waiting times, bad attitudes of health workers, high expense of treatment, and their overall satisfaction towards outpatient care was lower. In the terms of inpatient care, patients were more satisfied with treatment expense in CHCs compared with county hospitals. CONCLUSIONS: CHCs and hospitals face different challenges regarding patient satisfaction. Further healthcare reform in China need to adopt more measures (e.g. increasing quality of primary care, setting up a referral medical system etc.) to improve patient satisfaction.
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Servicios de Salud Comunitaria/estadística & datos numéricos , Hospitales/estadística & datos numéricos , Satisfacción del Paciente/estadística & datos numéricos , Atención Primaria de Salud/estadística & datos numéricos , Adolescente , Adulto , Anciano , Actitud del Personal de Salud , China , Servicios de Salud Comunitaria/economía , Estudios Transversales , Femenino , Financiación Personal , Estado de Salud , Humanos , Pacientes Internos , Masculino , Persona de Mediana Edad , Pacientes Ambulatorios , Atención Primaria de Salud/economía , Factores Socioeconómicos , Factores de Tiempo , Listas de Espera , Adulto JovenRESUMEN
OBJECTIVE: Octamer transcription factor 1 (OCT1) was found to be expressed in intestinal metaplasia and gastric cancer (GC), but the exact roles of OCT1 in GC remain unclear. The objective of this study was to determine the functional and prognostic implications of OCT1 in GC. DESIGN: Expression of OCT1 was examined in paired normal and cancerous gastric tissues and the prognostic significance of OCT1 was analysed by univariate and multivariate survival analyses. The functions of OCT1 on synbindin expression and extracellular signal-regulated kinase (ERK) phosphorylation were studied in vitro and in xenograft mouse models. RESULTS: The OCT1 gene is recurrently amplified and upregulated in GC. OCT1 overexpression and amplification are associated with poor survival in patients with GC and the prognostic significance was confirmed by independent patient cohorts. Combining OCT1 overexpression with American Joint Committee on Cancer staging improved the prediction of survival in patients with GC. High expression of OCT1 associates with activation of the ERK mitogen-activated protein kinase signalling pathway in GC tissues. OCT1 functions by transactivating synbindin, which binds to ERK DEF domain and facilitates ERK phosphorylation by MEK. OCT1-synbindin signalling results in the activation of ERK substrates ELK1 and RSK, leading to increased cell proliferation and invasion. Immunofluorescent study of human GC tissue samples revealed strong association between OCT1 protein level and synbindin expression/ERK phosphorylation. Upregulation of OCT1 in mouse xenograft models induced synbindin expression and ERK activation, leading to accelerated tumour growth in vivo. CONCLUSIONS: OCT1 is a driver of synbindin-mediated ERK signalling and a promising marker for the prognosis and molecular subtyping of GC.
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Quinasas MAP Reguladas por Señal Extracelular/fisiología , Sistema de Señalización de MAP Quinasas/fisiología , Proteínas del Tejido Nervioso/fisiología , Transportador 1 de Catión Orgánico/fisiología , Neoplasias Gástricas/fisiopatología , Proteínas de Transporte Vesicular/fisiología , Animales , Ratones , PronósticoRESUMEN
It is increasingly evident that long noncoding RNAs (lncRNA) have causative roles in carcinogenesis. In this study, we report findings implicating a novel lncRNA in gastric cancer, termed GAPLINC (gastric adenocarcinoma predictive long intergenic noncoding RNA), based on the use of global microarray and in situ hybridization (ISH) analyses to identify aberrantly expressed lncRNA in human gastric cancer specimens. GAPLINC is a 924-bp-long lncRNA that is highly expressed in gastric cancer tissues. GAPLINC suppression and with gene expression profiling in gastric cancer cells revealed alterations in cell migration pathways, with CD44 expression the most highly correlated. Manipulating GAPLINC expression altered CD44 mRNA abundance and the effects of GAPLINC on cell migration and proliferation were neutralized by suppressing CD44 expression. Mechanistic investigations revealed that GAPLINC regulates CD44 as a molecular decoy for miR211-3p, a microRNA that targets both CD44 and GAPLINC. Tissue ISH analysis suggested that GAPLINC overexpression defines a subgroup of patients with gastric cancer with very poor survival. Taken together, our results identify a noncoding regulatory pathway for the CD44 oncogene, shedding new light on the basis for gastric cancer cell invasiveness.
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Receptores de Hialuranos/genética , ARN Largo no Codificante/genética , ARN Neoplásico/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica , Células HCT116 , Humanos , MicroARNs/genética , Invasividad Neoplásica , Pronóstico , ARN Mensajero/genéticaRESUMEN
In this study we investigated the biological role and mechanism of miR-198 in colorectal carcinoma (CRC). MiR-198 expression was shown to exhibit a strongly negative correlation with lymph node invasion, distant metastasis and patient survival in examinations of colorectal cancer tissues and paired normal colorectal mucosa tissues. fucosyl transferase 8 (FUT8) was identified as a potential target of miR-198 in bioinformatics analysis and luciferase reporter assays. Overexpression of miR-198 in CRC cell lines decreased FUT8 levels as shown by immunofluorescence analysis, and inhibited cell proliferation, migration, and invasion. These anti-tumor phenotypes were rescued by reconstitution of FUT8 expression. Furthermore, miR-198 was shown to target the 3'UTR of FUT8 directly to downregulate FUT8 expression at both mRNA and protein levels in qRT-PCR and Western blot analyses, respectively. In vivo, restoration of miR-198 significantly inhibited xenograft growth and invasion of CRC tumors in nude mice. Therefore, it could be concluded that miR-198 suppresses the proliferation and invasion of CRC by directly targeting FUT8.
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Movimiento Celular/genética , Proliferación Celular/genética , Neoplasias Colorrectales/genética , Fucosiltransferasas/genética , MicroARNs/genética , Metástasis de la Neoplasia/genética , Regiones no Traducidas 3'/genética , Animales , Línea Celular Tumoral , Neoplasias Colorrectales/patología , Regulación hacia Abajo/genética , Regulación Neoplásica de la Expresión Génica/genética , Células HCT116 , Humanos , Ratones , Ratones Desnudos , Metástasis de la Neoplasia/patologíaRESUMEN
Covalent modification adding acetyl groups to the C terminus of the p53 protein has been suggested to be required for its functional activation as a tumour suppressor. However, it remains largely unknown how p53 acetylation is deregulated in colorectal cancer (CRC), which is the third most commonly diagnosed cancer worldwide. Here we show that ArhGAP30, a Rho GTPase-activating protein, is a pivotal regulator for p53 acetylation and functional activation in CRC. ArhGAP30 binds to p53 C-terminal domain and P300, facilitating P300-mediated acetylation of p53 at lysine 382. ArhGAP30 expression is required for p53 activation upon DNA damage stress, and the level of ArhGAP30 correlates with p53 acetylation and functional activation in CRC tissues. Moreover, low level of ArhGAP30 expression associates with poor survival of CRC patients. In summary, ArhGAP30 is required for p53 acetylation and functional activation in CRC, and the expression of ArhGAP30 is a potential prognostic marker for CRC.
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Neoplasias Colorrectales/metabolismo , Proteínas Activadoras de GTPasa/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Acetilación , Animales , Apoptosis/fisiología , Puntos de Control del Ciclo Celular , Movimiento Celular , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Daño del ADN , Proteínas Activadoras de GTPasa/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Masculino , Ratones Endogámicos BALB C , Valores de Referencia , Proteína p53 Supresora de Tumor/genéticaRESUMEN
The extracellular signal-regulated kinase (ERK), mitogen-activated protein kinase (MAPK) pathway is an important cell proliferation pathway. We previously reported that the transport protein particle complex 4 (TRAPPC4), ERK2 interaction may activate ERK1/2, modulate pERK2 nuclear localization and regulate proliferation and apoptosis in colorectal cancer (CRC) cells. The present study further investigated the function of the TRAPPC4-ERK2 interaction in CRC in vitro and in vivo. Silencing of TRAPPC4 induced G0/G1 phase cell cycle arrest, upregulated p21 and downregulated cyclin B1 in CRC cells. Overexpression of TRAPPC4 after ERK2 silencing decreased the percentage of G0/G1 phase cells, increased the percentage of G2/M and S phase cells, downregulated p21, upregulated cyclin B1, and enhanced CRC cell viability. Immunohistochemical staining revealed that knockdown of TRAPPC4 downregulated pERK2, whereas overexpression of TRAPPC4 upregulated pERK2. Epidermal growth factor (EGF) stimulated upregulation of TRAPPC4 and pERK2 in SW1116 cells; EGF stimulation or overexpression of TRAPPC4 induced pERK2 nuclear translocation. Silencing of TRAPPC4 reduced SW1116 xenograft tumor growth in vivo, whereas overexpression of TRAPPC4 increased tumor growth, compared to control tumors. Moreover, modulation of TRAPPC4 expression in vivo affected the levels of pERK2 in the cytoplasm and nucleus and expression of p21. These results conclusively demonstrate that TRAPPC4 regulates ERK2 activation and also affects the distribution of activated pERK2 in CRC cells. The ability of ERK2 to play a role in colorectal carcinogenesis depends, at least in part, on TRAPPC4.
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Neoplasias Colorrectales/metabolismo , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Proteínas del Tejido Nervioso/fisiología , Proteínas de Transporte Vesicular/fisiología , Animales , Apoptosis , Western Blotting , Ciclo Celular , Núcleo Celular/metabolismo , Proliferación Celular , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Factor de Crecimiento Epidérmico/farmacología , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Proteína Quinasa 1 Activada por Mitógenos/antagonistas & inhibidores , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Proteínas del Tejido Nervioso/antagonistas & inhibidores , Fosforilación , ARN Interferente Pequeño/genética , Transducción de Señal , Activación Transcripcional , Células Tumorales Cultivadas , Proteínas de Transporte Vesicular/antagonistas & inhibidoresRESUMEN
The development of gastric cancer (GC) is a complex multistep process, including numerous genetic and epigenetic changes. CD24 is associated with enhanced invasiveness of GC and a poor prognosis. However, the mechanism by which CD24 induces GC progression remains poorly characterized. Here, we found that the expression of CD24 gradually increased in samples of normal gastric mucosa, non-atrophic chronic gastritis, chronic atrophic gastritis (CAG), CAG with intestinal metaplasia, dysplasia and GC. Moreover, the knockdown of CD24 induced significant levels of apoptosis in GC cells via the mitochondrial apoptotic pathway. CD24 may also promote cellular invasion and regulate the expression of E-cadherin, fibronectin and vitamin D receptor in GC cells. The activation of signal transducer and activator of transcription 3 (STAT3) may mediate CD24-induced GC survival and invasion in vitro. Furthermore, CD24-induced GC progression and STAT3 activation could also be detected in vivo and in clinical GC tissues samples. Taken together, our results indicate that CD24 mediates gastric carcinogenesis and may promote GC progression by suppressing apoptosis and promoting invasion, with the activation of STAT3 playing a critical role.
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Antígeno CD24/metabolismo , Carcinogénesis/metabolismo , Factor de Transcripción STAT3/metabolismo , Neoplasias Gástricas/metabolismo , Adulto , Anciano , Animales , Apoptosis , Antígeno CD24/genética , Carcinogénesis/patología , Caspasa 3/metabolismo , Línea Celular Tumoral , Proliferación Celular , Supervivencia Celular , Enfermedad Crónica , Progresión de la Enfermedad , Femenino , Gastritis/metabolismo , Xenoinjertos , Humanos , Mucosa Intestinal/metabolismo , Masculino , Metaplasia , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Mitocondrias/metabolismo , Trasplante de Neoplasias , Neoplasias Gástricas/patologíaRESUMEN
BACKGROUND: The molecular mechanisms that control the aggressiveness of gastric cancer (GC) remain poorly defined. Here we show that synbindin contributes to the aggressiveness of GC by activating extracellular signal-regulated protein kinase (ERK) signaling on the Golgi apparatus. METHODS: Expression of synbindin was examined in normal gastric mucosa (n = 44), intestinal metaplastic gastric mucosa (n = 66), and GC tissues (n=52), and the biological effects of synbindin on tumor growth and ERK signaling were detected in cultured cells, nude mice, and human tissue samples. The interaction between synbindin and mitogen-activated protein kinase kinase (MEK1)/ERK was determined by immunofluorescence and fluorescence resonance energy transfer assays. The transactivation of synbindin by nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) was detected using luciferase reporter assay and chromatin immunoprecipitation. RESULTS: High expression of synbindin was associated with larger tumor size (120.8 vs 44.8 cm(3); P = .01), advanced tumor node metastasis (TNM) stage (P = .003), and shorter patient survival (hazard ratio = 1.51; 95% confidence interval [CI] = 1.01 to 2.27; P = .046). Synbindin promotes cell proliferation and invasion by activating ERK2 on the Golgi apparatus, and synbindin is directly transactivated by NF-κB. Synbindin expression level was statistically significantly higher in human GCs with activated ERK2 than those with low ERK2 activity (intensity score of 11.5, 95% CI = 10.4 to 12.4 vs intensity score of 4.6, 95% CI 3.9 to 5.3; P < .001). Targeting synbindin in xenograft tumors decreased ERK2 phosphorylation and statistically significantly reduced tumor volume (451.2mm(3), 95% CI = 328.3 to 574.1 vs 726.1mm(3), 95% CI = 544.2 to 908.2; P = .01). CONCLUSIONS: Synbindin contributes to malignant phenotypes of GC by activating ERK on the Golgi, and synbindin is a potential biomarker and therapeutic target for GC.
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Aparato de Golgi/metabolismo , MAP Quinasa Quinasa 1/metabolismo , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , FN-kappa B/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Proteínas de Transporte Vesicular/metabolismo , Animales , Línea Celular Tumoral , Inmunoprecipitación de Cromatina , Citometría de Flujo , Transferencia Resonante de Energía de Fluorescencia , Técnica del Anticuerpo Fluorescente , Mucosa Gástrica/metabolismo , Regulación Enzimológica de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Aparato de Golgi/enzimología , Xenoinjertos , Humanos , Estimación de Kaplan-Meier , Luciferasas , Sustancias Luminiscentes , Sistema de Señalización de MAP Quinasas , Ratones , Ratones Desnudos , Proteínas del Tejido Nervioso/genética , Oportunidad Relativa , Fosforilación , Análisis por Matrices de Proteínas , Estudios Retrospectivos , Neoplasias Gástricas/enzimología , Neoplasias Gástricas/mortalidad , Activación Transcripcional , Regulación hacia Arriba , Proteínas de Transporte Vesicular/genéticaRESUMEN
The mechanism by which butyrate prevents colorectal cancer (CRC) is unclear. The objective of this study was to identify potential target genes of butyrate in 1,2-dimethylhydrazine (DMH)-induced CRC in mice. Nontumor colorectal tissues of mice from DMH + butyrate, DMH, and control groups were hybridized on Agilent Mouse Whole Genome 44K Oligo Microarrays. Selected genes were validated by qRT-PCR. Data was further analyzed by KEGG, gene ontology (GO), and pathway studio software. The tumor incidence in the DMH + butyrate and DMH groups was 30% and 90%, respectively (P < 0.05). There were 355 genes downregulated due to DMH treatment while upregulated by butyrate, and 475 genes upregulated by DMH while downregulated by butyrate. The results revealed that most of the tumor-related signaling pathways (e.g., MAPK pathway, Wnt pathway, insulin pathway, and VEGF pathway) were downregulated by butyrate. The GO terms related to cell differentiation, cell cycle, cell proliferation, cell death, cell adhesion, and cell migration were significantly affected. The chemopreventive effects of butyrate were confirmed in the DMH-induced CRC mice model. And mechanisms encompassing multiple pathways and GO terms are involved in the regulation of gene expression.
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Butiratos/farmacología , Neoplasias Colorrectales/genética , Regulación Neoplásica de la Expresión Génica , 1,2-Dimetilhidrazina/toxicidad , Animales , Adhesión Celular/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Neoplasias Colorrectales/inducido químicamente , Modelos Animales de Enfermedad , Regulación hacia Abajo/efectos de los fármacos , Femenino , Perfilación de la Expresión Génica , Genes Relacionados con las Neoplasias , Ratones , Ratones Endogámicos ICR , Análisis por Micromatrices , Transducción de Señal/genéticaRESUMEN
Gastric cancer (GC) remains a major cause of morbidity and mortality worldwide and there is therefore a clear need to search for more sensitive early diagnostic biomarkers. We performed a systematic review of eight published miRNA profiling studies that compared GC tissues with adjacent noncancerous tissues. A miRNA ranking system was used that took the frequency of comparisons, direction of differential expression and total sample size into consideration. We identified five miRNAs that were most consistently reported to be upregulated (miR-21, miR-106b, miR-17, miR-18a and miR-20a) and two miRNAs that were downregulated (miR-378 and miR-638). Six of these were further validated in 32 paired sets of GC and adjacent noncancerous tissue samples using real-time PCR. MiR-21, miR-106b, miR-17, miR-18a and miR-20a were confirmed to be upregulatedin GC tissues, while the expression of miR-378 was decreased. Moreover, we found a significant association between expression levels of miR-21, miR-106b, miR-17, miR-18a and miR-20a and clinicopathological features of GC. These miRNAs may be used for diagnostic and/or prognostic biomarkers for GC and therefore warrant further investigation.
Asunto(s)
Biomarcadores de Tumor/genética , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , Neoplasias Gástricas/genética , Transcriptoma , Humanos , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Pronóstico , Reproducibilidad de los Resultados , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Neoplasias Gástricas/diagnósticoRESUMEN
BACKGROUND/AIMS: To evaluate the efficacy of on-demand strategy with proton pump inhibitors (PPIs) in mild gastroesophageal reflux disease (GERD). METHODOLOGY: A literature search was conducted to identify randomized controlled clinical trials which investigating on-demand treatment with PPIs in mild GERD. The control group should be placebo or once-daily treatment. Comparison of treatment effect was performed. RESULTS: Eight studies met the inclusion criteria, of which six were compared with placebo, two others with once-daily treatment. The percentage of patients unwilling to continue the study was 12.1% in the on-demand group while 39.6% in the placebo group. The meta-analysis revealed a statistically significant difference between the two groups (RR: 0.32; 95% CI: 0.23, 0.43). We obtained a similar result when compared with once-daily treatment (RR: 0.52; 95% CI: 0.34, 0.79). CONCLUSIONS: This meta-analysis indicates that on-demand therapy with PPIs is superior to placebo or once-daily treatment in terms of mild GERD.
Asunto(s)
Reflujo Gastroesofágico/tratamiento farmacológico , Inhibidores de la Bomba de Protones/administración & dosificación , Esquema de Medicación , Humanos , Inhibidores de la Bomba de Protones/uso terapéuticoRESUMEN
Many Rho GTPase activation proteins (RhoGAPs) are deleted or downregulated in cancers, but the functional consequences are still unclear. Here, we show that the RhoGAP ArhGAP11A induces cell-cycle arrest and apoptosis by binding to the tumor suppressor p53. The RhoGAP domain of ArhGAP11A binds to the tetramerization domain of p53, but not to its family members p63 or p73. The interaction stabilizes the tetrameric conformation of p53 and enhances its DNA-binding activity, thereby inducing cell-cycle arrest and apoptosis. Upon DNA damage stress, ArhGAP11A accumulates in the nucleus and interacts with p53, whereas knockdown of ArhGAP11A partially blocks p53 transcriptional activity. These findings explain why RhoGAPs are frequently deleted in cancers and suggest that the RhoGAP family sits at the crossroads between the cell-migration and proliferation pathways.