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OBJECTIVE: The aim of this study was to explore barriers and facilitators to implementing enhanced recovery pathways, with a focus on identifying factors that distinguished hospitals achieving greater levels of implementation success. BACKGROUND: Despite the clinical effectiveness of enhanced recovery pathways, the implementation of these complex interventions varies widely. While there is a growing list of contextual factors that may affect implementation, little is known about which factors distinguish between higher and lower levels of implementation success. METHODS: We conducted in-depth interviews with 168 perioperative leaders, clinicians, and staff from 8 US hospitals participating in the Agency for Healthcare Research and Quality Safety Program for Improving Surgical Care and Recovery. Guided by the Consolidated Framework for Implementation Research, we coded interview transcripts and conducted a thematic analysis of implementation barriers and facilitators. We also rated the perceived effect of factors on different levels of implementation success, as measured by hospitals' adherence with 9 process measures over time. RESULTS: Across all hospitals, factors with a consistently positive effect on implementation included information-sharing practices and the implementation processes of planning and engaging. Consistently negative factors included the complexity of the pathway itself, hospitals' infrastructure, and the implementation process of "executing" (particularly in altering electronic health record systems). Hospitals with the greatest improvement in process measure adherence were distinguished by clinicians' positive knowledge and beliefs about pathways and strong leadership support from both clinicians and executives. CONCLUSION: We draw upon diverse perspectives from across the perioperative continuum of care to qualitatively describe implementation factors most strongly associated with successful implementation of enhanced recovery pathways.
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Hospitais , Humanos , Pesquisa QualitativaRESUMO
BACKGROUND: A growing number of US states are implementing programs to address the social needs (SNs) of their Medicaid populations through managed care contracts. Incorporating SN might also improve risk adjustment methods used to reimburse Medicaid providers. OBJECTIVES: Identify classes of SN present within the Medicaid population and evaluate the performance improvement in risk adjustment models of health care utilization and cost after incorporating SN classes. RESEARCH DESIGN: A secondary analysis of Medicaid patients during the years 2018 and 2019. Latent class analysis (LCA) was used to identify SN classes. To evaluate the impact of SN classes on measures of hospitalization, emergency (ED) visits, and costs, logistic and linear regression modeling for concurrent and prospective years was used. Model performance was assessed before and after incorporating these SN classes to base models controlling for demographics and comorbidities. SUBJECTS: 262,325 Medicaid managed care program patients associated with a large urban academic medical center. RESULTS: 7.8% of the study population had at least one SN, with the most prevalent being related to safety (3.9%). Four classes of SN were determined to be optimal based on LCA, including stress-related needs, safety-related needs, access to health care-related needs, and socioeconomic status-related needs. The addition of SN classes improved the performance of concurrent base models' AUC (0.61 vs. 0.58 for predicting ED visits and 0.61 vs. 0.58 for projecting hospitalizations). CONCLUSIONS: Incorporating SN clusters significantly improved risk adjustment models of health care utilization and costs in the study population. Further investigation into the predictive value of SN for costs and utilization in different Medicaid populations is merited.
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Gliomas are the most prevalent type of primary brain tumors and are resistant to radiation therapy. ß1,6-GlcNAc branched N-glycans, which are encoded by N-acetylglucosaminyltransferase V (GnT-V), play important roles in glioma progression. However, the relationship between ß1,6-GlcNAc branched expression and radiosensitivity in glioma cells is still unknown. In this study, the expression of ß1,6-GlcNAc branched N-glycans in nonneoplastic brain and glioma samples was characterized by lectin histochemistry. The radiosensitivity of glioma cells was evaluated by colony formation assay. We found that ß1,6-GlcNAc branches were highly expressed in glioblastoma specimens, compared with diffuse astrocytomas and nonneoplastic brain. In addition, ß1,6-GlcNAc branched expression was negatively correlated with the radiosensitivity of glioblastoma cells. Furthermore, the inhibition of N-linked ß1,6-GlcNAc branches by GnT-V silencing in U251 cells could reduce the cell clonogenic survival after X-irradiation. Meanwhile, the G2/M checkpoint was impaired and there was an increase in the number of apoptotic cells. Tunicamycin, an inhibitor of N-glycan biosynthesis, was also able to enhance the radiosensitivity of U251 cells. Thus, our results suggest that development of therapeutic approaches targeting N-linked ß1,6-GlcNAc branches may be a promising strategy in glioblastoma treatment.
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Glioma/genética , N-Acetilglucosaminiltransferases/biossíntese , Polissacarídeos/biossíntese , Tolerância a Radiação/genética , Adulto , Idoso , Apoptose/efeitos da radiação , Linhagem Celular Tumoral , Proliferação de Células/efeitos da radiação , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Glioma/tratamento farmacológico , Glioma/patologia , Glioma/radioterapia , Humanos , Masculino , Pessoa de Meia-Idade , N-Acetilglucosaminiltransferases/antagonistas & inibidores , N-Acetilglucosaminiltransferases/genética , Polissacarídeos/genética , Radiação , Ensaio Tumoral de Célula-Tronco , Tunicamicina/administração & dosagemRESUMO
OBJECTIVES: Enhanced recovery pathways (ERPs) are evidence-based approaches to improving perioperative surgical care. However, the role of electronic health records (EHRs) in their implementation is unclear. We examine how EHRs facilitate or hinder ERP implementation. MATERIALS AND METHODS: We conducted interviews with informaticians and clinicians from US hospitals participating in an ERP implementation collaborative. We used inductive thematic analysis to analyze transcripts and categorized hospitals into 3 groups based on process measure adherence. High performers exhibited a minimum 80% adherence to 6 of 9 metrics, high improvers demonstrated significantly better adherence over 12 months, and strivers included all others. We mapped interrelationships between themes using causal loop diagrams. RESULTS: We interviewed 168 participants from 8 hospitals and found 3 thematic clusters: (1) "EHR difficulties" with the technology itself and contextual factors related to (2) "EHR enablers," and (3) "EHR barriers" in ERP implementation. Although all hospitals experienced issues, high performers and improvers successfully integrated ERPs into EHRs through a dedicated multidisciplinary team with informatics expertise. Strivers, while enacting some fixes, were unable to overcome individual resistance to EHR-supported ERPs. DISCUSSION AND CONCLUSION: We add to the literature describing the limitations of EHRs' technological capabilities to facilitate clinical workflows. We illustrate how organizational strategies around engaging motivated clinical teams with informatics training and resources, especially with dedicated technical support, moderate the extent of EHRs' support to ERP implementation, causing downstream effects for hospitals to transform technological challenges into care-improving opportunities. Early and consistent involvement of informatics expertise with frontline EHR clinician users benefited the efficiency and effectiveness of ERP implementation and sustainability.
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Registros Eletrônicos de Saúde , Hospitais , Humanos , MotivaçãoRESUMO
BACKGROUND: Limonin is one of the most abundant active ingredients of Tetradium ruticarpum. It exerts antitumor effects on several kinds of cancer cells. However, whether limonin exerts antitumor effects on colorectal cancer (CRC) cells and cancer stem-like cells (CSCs), a subpopulation responsible for a poor prognosis, is unclear. AIM: To evaluate the effects of limonin on CSCs derived from CRC cells. METHODS: CSCs were collected by culturing CRC cells in serum-free medium. The cytotoxicity of limonin against CSCs and parental cells (PCs) was determined by cholecystokinin octapeptide-8 assay. The effects of limonin on stemness were detected by measuring stemness hallmarks and sphere formation ability. RESULTS: As expected, limonin exerted inhibitory effects on CRC cell behaviors, including cell proliferation, migration, invasion, colony formation and tumor formation in soft agar. A relatively low concentration of limonin decreased the expression stemness hallmarks, including Nanog and ß-catenin, the proportion of aldehyde dehydrogenase 1-positive CSCs, and the sphere formation rate, indicating that limonin inhibits stemness without presenting cytotoxicity. Additionally, limonin treatment inhibited invasion and tumor formation in soft agar and in nude mice. Moreover, limonin treatment significantly inhibited the phosphorylation of STAT3 at Y705 but not S727 and did not affect total STAT3 expression. Inhibition of Nanog and ß-catenin expression and sphere formation by limonin was obviously reversed by pretreatment with 2 µmol/L colievlin. CONCLUSION: Taken together, these results indicate that limonin is a promising compound that targets CSCs and could be used to combat CRC recurrence and metastasis.
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The role of AXL in various oncogenic processes has made it an attractive target for cancer therapy. Currently, kinase selectivity profiles, especially circumventing MET inhibition, remain a scientific issue of great interest in the discovery of selective type II AXL inhibitors. Starting from a dual MET/AXL-targeted lead structure from our previous work, we optimized a 1,6-naphthyridinone series using molecular modeling-assisted compound design to improve AXL potency and selectivity over MET, resulting in the potent and selective type II AXL-targeted compound 25c. This showed excellent AXL inhibitory activity (IC50 = 1.1 nM) and 343-fold selectivity over the highly homologous kinase MET in biochemical assays. Moreover, compound 25c significantly inhibited AXL-driven cell proliferation, dose-dependently suppressed 4T1 cell migration and invasion, and induced apoptosis. Compound 25c also showed noticeable antitumor efficacy in a BaF3/TEL-AXL xenograft model at well-tolerated doses. Overall, this study presented a potent and selective type II AXL-targeted lead compound for further drug discovery.
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Antineoplásicos , Inibidores de Proteínas Quinases , Humanos , Linhagem Celular Tumoral , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/química , Relação Estrutura-Atividade , Proliferação de Células , Modelos Moleculares , Antineoplásicos/farmacologia , Antineoplásicos/química , Estrutura MolecularRESUMO
As an inflammatory bowel disease, ulcerative colitis (UC) does not respond well to current treatments. It is of positive clinical significance to further study the pathogenesis of UC and find new therapeutic targets. B lymphocytes play an important role in the pathogenesis of UC. The effect of anti-CD20 therapy on UC also provides new evidence for the involvement of B cells in UC process additionally, suggesting the important role and potential therapeutic value of B cells in UC. In this study, we screened the most critical immune cell-related gene modules associated with UC and found that activated B cells were closely related to the gene modules. Subsequently, key activated B cell-associated gene (BRG) signatures were obtained based on WGCNA and differential expression analysis, and three overlapping BRG-associated genes were obtained by RF and LASSO algorithms as BRG-related diagnostic biomarkers for UC. Nomogram model was further performed to evaluate the diagnostic ability of BRG-related diagnostic biomarkers, subsequently followed by UC molecular subsets identification and immunoinfiltration analysis. We also further verified the expressions of the three screened BRGs in vitro by using an LPS-induced NCM460 cell line model. Our results provide new evidence and potential intervention targets for the role of B cells in UC from a new perspective.
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Colite Ulcerativa , Doenças Inflamatórias Intestinais , Humanos , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/genética , Doenças Inflamatórias Intestinais/complicações , Redes Reguladoras de Genes , BiomarcadoresRESUMO
BACKGROUND: It has been well documented that the diagnosis of cancer is psychologically devastating to both the patients and caregivers. The incidence and mortality of esophageal cancer were 20.85 and 16.24 per 100,000 persons and the sixth most commonly diagnosed cancer and the fourth main cause of cancer death in China. We surveyed patients-caregivers dyad and examined the determinants of their depression and hopelessness. RESULTS: The prevalence of depression among patients and caregivers was 52.8% and 47.2%, and the prevalence for hopelessness was 64.4% and 53.9%, respectively Regression models indicate that the variables measured could explain 58.9% and 51.7% of the variance in depression and 66.8% and 45.7% of the variance in hopelessness among patients and caregivers, respectively. Overall, hopelessness was a determinant of depression and vice versa to both patients and caregivers. CONCLUSION: Esophageal patients' depression and hopelessness could also affect caregivers' depression and hopelessness despite the social support that family caregivers have. Psychosocial interventions should be planned to both Chinese patients and caregivers considering the predictors found in this study.
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Povo Asiático/psicologia , Atitude Frente a Morte , Cuidadores/psicologia , Depressão/etnologia , Neoplasias Esofágicas/psicologia , Pacientes Internados/psicologia , Adaptação Psicológica , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Estudos Transversais , Depressão/diagnóstico , Depressão/psicologia , Neoplasias Esofágicas/epidemiologia , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Análise de Regressão , Fatores de Risco , Apoio Social , Fatores Socioeconômicos , Inquéritos e QuestionáriosRESUMO
Background: Testicular torsion is the reduction of blood flow to the testis after spermatic cord torsion. For patients, the diagnosis of testicular torsion is controversial and complicated by the fact that ultrasound blood flow signals are not significantly reduced in comparison to the unaffected, healthy, testis, despite persistent symptoms on the affected side. Our study aims to investigate the diagnostic characteristics of high-resolution ultrasonography (US) in pediatric testicular torsion with the preserved flow to increase diagnostic accuracy. Methods: Seven pediatric patients aged 49 days to 15 years old, with the preserved blood flow, but surgically diagnosed as testicular torsion, from October 2017 to August 2019, were retrospectively included in the study. The imaging manifestations of high-frequency ultrasonography were evaluated. Results: All cases had preserved testicular blood flow, but the surgical findings showed various degrees of twist, from 90 to 540 degrees. Preoperative ultrasound showed spermatic cord distortion in all cases, and testicular long axis tilting in four cases (4/7 = 57.1%). Conclusion: In some testicular torsion cases, Color Doppler may show normal or increased blood flow signals in the testis. We should further observe the morphology and position of the testes and epididymides, the echo of the testicular parenchyma, and, especially evaluate the "whirlpool sign" in the spermatic cord, to avoid missing testicular torsion with blood flow signals.
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A novel class of benzyl-free and benzyl-substituted carbamylated tryptamine derivatives (CDTs) was designed and synthesized to serve as effective building blocks for the development of novel multi-target directed ligands (MTDLs) for the treatment of neurological disorders linked to cholinesterase (ChE) activity. The majority of them endowed butyrylcholinesterase (BuChE) with more substantial inhibition potency than acetylcholinesterase (AChE), according to the full study of ChE inhibition. Particularly, hybrids with dibenzyl groups (2b-2f, 2j, 2o, and 2q) showed weak or no neuronal toxicity and hepatotoxicity and single-digit nanomolar inhibitory effects against BuChE. Through molecular docking and kinetic analyses, the potential mechanism of action on BuChE was first investigated. In vitro H2O2-induced HT-22 cells assay demonstrated the favorable neuroprotective potency of 2g, 2h, 2j, 2m, 2o, and 2p. Besides, 2g, 2h, 2j, 2m, 2o, and 2p endowed good antioxidant activities and COX-2 inhibitory effects. This study suggested that this series of hybrids can be applied to treat various ChE-associated neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD), as well as promising building blocks for further structure modification to develop efficient MTDLs.
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Patients enrolled in Medicaid have significantly higher social needs (SNs) than others. Using claims and electronic health records (EHRs) data, managed care organizations (MCOs) could systemically identify high-risk patients with SNs and develop population health management interventions. Impact of SNs on models predicting health care utilization and costs was assessed. This retrospective study included claims and EHRs data on 39,267 patients younger than age 65 years who were continuously enrolled during 2018-2019 in a Medicaid-managed care plan. SN marker was developed suggesting presence of International Classification of Diseases, 10th revision codes in any of the 5 SN domains. Impact of SN marker was compared across demographic and 2 diagnosis-based (ie, Charlson and Adjusted Clinical Groups risk score) prediction models of emergency department (ED) visit and hospitalizations, and total, medical, and pharmacy costs. After combining data sources, prevalence of documented SN marker increased from 11% and 13% to 18% of the study population across claims, EHRs, and both combined, respectively. SN marker improved predictions of demographic models for all utilization and total costs outcomes (area under the curve [AUC] of ED model increased from 0.57 to 0.61 and R2 of total cost model increased from 10.9 to 12.2). In both diagnosis-based models, adding SN marker marginally improved outcomes prediction (AUC of ED model increased from 0.65 to 0.66). This study demonstrated feasibility of using claims and EHRs data to systematically capture SNs and incorporate in prediction models that could enable MCOs and policy makers to adjust and develop effective population health interventions.
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Registros Eletrônicos de Saúde , Medicaid , Idoso , Custos de Cuidados de Saúde , Humanos , Programas de Assistência Gerenciada , Aceitação pelo Paciente de Cuidados de Saúde , Estudos Retrospectivos , Estados UnidosRESUMO
BACKGROUND: Tuberous sclerosis complex (TSC) is a rare genetic disease which leads to formation of benign tumors in the brain and other organs of the body. Ultrasound (US) can detect the location, quantity, size and internal echo of TSC-associated renal diseases, liver angiomyolipoma (AML), and co-existing lesions, providing important diagnostic basis for clinical diagnosis. The aim of the present study was to investigate the abdominal ultrasonographic features of pediatric TSC and explore the advantages of abdominal ultrasonography in clinical practice. METHODS: Data of children with TSC, who presented to the Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, between January 2016 and November 2018, were analyzed by a retrospective chart review. The cases were identified from electronic medical records (EMR) system and underwent ultrasonography, we yielded a total of 12 patients. RESULTS: The 12 pediatric patients, including 5 boys and 7 girls, ranged in age from 9 months to 13 years old. And they all had a history of epilepsy. All the patients underwent brain magnetic resonance imaging (MRI) or computed tomography (CT) examination, which revealed a scattered distribution of multiple hyperintense nodules. Of the 12 patients, 10 had TSC-associated bilateral renal AMLs, 5 had hepatic AML, and 4 had renal cysts. CONCLUSIONS: US is a useful and non-invasive tool for the detection of TSC-associated renal and liver lesions and for clinical follow-up among pediatric patients.
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Mild mitochondrial stress experienced early in life can have beneficial effects on the life span of organisms through epigenetic regulations. Here, we report that acetyl-coenzyme A (CoA) represents a critical mitochondrial signal to regulate aging through the chromatin remodeling and histone deacetylase complex (NuRD) in Caenorhabditis elegans. Upon mitochondrial stress, the impaired tricarboxylic acid cycle results in a decreased level of citrate, which accounts for reduced production of acetyl-CoA and consequently induces nuclear accumulation of the NuRD and a homeodomain-containing transcription factor DVE-1, thereby enabling decreased histone acetylation and chromatin reorganization. The metabolic stress response is thus established during early life and propagated into adulthood to allow transcriptional regulation for life-span extension. Furthermore, adding nutrients to restore acetyl-CoA production is sufficient to counteract the chromatin changes and diminish the longevity upon mitochondrial stress. Our findings uncover the molecular mechanism of the metabolite-mediated epigenome for the regulation of organismal aging.
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Montagem e Desmontagem da Cromatina , Longevidade , Acetilcoenzima A/metabolismo , Acetilação , Animais , Caenorhabditis elegans/metabolismo , Cromatina/metabolismo , Histonas/metabolismoRESUMO
BACKGROUND: Previous studies have demonstrated that P21 (WAF1/CIP1) is a valuable prognostic factor in several malignant tumors. However, it is not known whether P21 can predict the prognosis in patients with esophageal cancer (EC). The aim of this research was to investigate the contribution of P21 expression to the clinicopathological characteristics and of EC. METHODS: A systematic review and meta-analysis of study focusing on P21 expression, clinicopathological characteristics, and clinical outcomes in patients with EC was performed using seven databases (PubMed, Embase, Web of Science, and four Chinese databases). Pooled hazard ratios and odds ratios were used to explore the association between P21 expression, clinicopathological characteristics, and outcomes in patients with EC. The heterogeneity of the studies was classified by the I 2 statistic. The sensitivity analysis was then utilized to assess the robustness of the results. Finally, the funnel plot and Begg's test were used to evaluate the publication bias. RESULTS: Forty-five studies with 3098 patients were eligible for inclusion in the meta-analysis. Thirty of these studies reported on clinicopathological characteristics and 15 on clinical outcomes. The pooled hazard ratio of 1.456 (95% confidence intervals 1.033-2.053, P = 0.032) for overall survival indicated that a low P21 expression level was an unfavorable prognostic factor for a clinical outcome in patients with EC. Furthermore, the pooled odds ratio confirmed an association between decreased P21 expression and poor clinicopathological characteristics, including differentiation, lymph node metastasis, invasion, and higher grade and clinical stage. Notably, high P21 expression was a significant predictor of a favorable response to chemotherapy. There was no evidence of publication bias. CONCLUSION: Reduced P21 expression is associated with a poor outcome in patients with EC.
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Biomarcadores Tumorais/genética , Inibidor de Quinase Dependente de Ciclina p21/genética , Neoplasias Esofágicas/metabolismo , Biomarcadores Tumorais/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Humanos , Metástase NeoplásicaRESUMO
Gastric cancer (GC) is a highly metastatic disease and one of the leading causes of cancer death in the world. Aberrant glycosylation is one of many molecular changes that accompany malignant transformation. This study was aimed at identification of glycan profiling changes in GC progression and its potential mechanisms. We employed a microarray with 91 lectins to compare the differential glycans in the three human GC cell lines, SGC-7901, BGC-823 and MGC-803. According to glycan-binding specificities of lectins, all GC cell lines expressed common sugar structures, such as mannose, galactose and fucose. Importantly, we found that the binding of Maackia amurensis lectin-I (MAL-I) to GC cells was proportional to their metastatic capacity. Further analysis revealed that the level of α2,3-linked sialic acids (α2-3Sia), which can be recognized by MAL-I, was significantly overexpressed in MGC-803 cells, while low expression was detected in SGC-7901 cells. In addition, the mRNA and protein expression levels of ß-galactoside α2,3-sialyltransferase IV (ST3Gal-IV), which was related to the synthesis of α2-3Sia, were substantially increased in MGC-803 cells. Knockdown of ST3Gal-IV in MGC-803 cells led to a decreased level of α2-3Sia and decreased ability of invasion and migration. Exogenous expression of ST3Gal-IV in SGC-7901 cells enhanced cell migration, invasion and the content of α2-3Sia. Furthermore, the staining of MAL-I in GC tissues showed that high expression of α2-3Sia was closely correlated with lymph node metastasis, TNM stage and poor overall survival. These findings lead to better understanding of the function of α2-3Sia in the progression and metastasis of GC. This property may be important for developing new therapeutic approaches for GC.
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Hexoses/metabolismo , Lectinas/metabolismo , Ácidos Siálicos/biossíntese , Sialiltransferases/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Biomarcadores Tumorais/biossíntese , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Movimento Celular , Feminino , Galactosídeos/metabolismo , Glicosilação , Humanos , Metástase Linfática , Maackia/química , Masculino , Análise em Microsséries , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Estadiamento de Neoplasias , Polissacarídeos/metabolismo , Prognóstico , RNA Mensageiro/metabolismo , Neoplasias Gástricas/tratamento farmacológico , beta-Galactosídeo alfa-2,3-SialiltransferaseRESUMO
Gastric cancer (GC) is one of the most common malignancies worldwide. The expression of CD147 protein is associated with GC. However, the clinical role of CD147 in GC has not been investigated extensively. Hence, we focused on studying the association between the expression of CD147 and clinicopathological features of GC patients in this study. Firstly, sixteen publications (1752 cases and 391 controls) and one from our own original research (143 cases) were included in the meta-analysis to obtain a more precise estimation of the diagnostic value of CD147. The results showed that expression rate of CD147 in the GC group is higher than that in control group. Moreover, gender, TNM stage, lymph node metastasis, and depth of invasion are all associated with CD147. Further, sections of gastric tissue from 143 cases underwent immunohistochemical staining for evaluation of CD147 protein expression. Our retrospective analysis demonstrated CD147 protein expression was significantly associated with clinical N stage, and tumor stage. Meanwhile, it can also serve as an independent prognosis biomarker. In conclusion, our results support the role of CD147 as a good indicator of diagnosis and prognosis.
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Basigina/genética , Biomarcadores Tumorais , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Basigina/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Invasividade Neoplásica , Estadiamento de Neoplasias , Razão de Chances , Prognóstico , Viés de Publicação , Neoplasias Gástricas/mortalidadeRESUMO
Radiotherapy is the primary treatment for human nasopharyngeal carcinoma (NPC), yet radioresistance remains a major obstacle to successful treatment in many cases. N-acetylglucosaminyltransferase V (GnT-V), which synthesizes ß1, 6-GlcNAc branched N-glycans, is closely related to the radiosensitivity of NPC cells. However, a better understanding of the functional role of GnT-V in NPC radioresistance and the related mechanisms is urgently needed. In the present study, a radioresistant NPC cell line, CNE-2R, was established by repeated γ-irradiation. We found that GnT-V levels, as well as ß1, 6-GlcNAc branched N-glycans were significantly increased in the CNE-2R cells as compared with that in the parental cells. Meanwhile, knockdown of GnT-V in the CNE-2R cells enhanced cell radiosensitivity and inhibited the formation of ß1, 6-branched N-glycans. In addition, the regulated expression of GnT-V in the CNE-2R cells converted the heterogeneous N-glycosylated forms of CD147. Furthermore, swainsonine, an inhibitor of N-glycan biosynthesis, was also able to reverse the radioresistance of the CNE-2R cells. Taken together, the present study revealed a novel mechanism of GnT-V as a regulator of radioresistance in NPC cells, which may be useful for fully understanding the biological role of N-glycans in NPC radioresistance.
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N-Acetilglucosaminiltransferases/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Polissacarídeos/metabolismo , Tolerância a Radiação/fisiologia , Apoptose/efeitos da radiação , Western Blotting , Carcinoma , Linhagem Celular Tumoral , Citometria de Fluxo , Humanos , Carcinoma Nasofaríngeo , RNA Interferente Pequeno , Reação em Cadeia da Polimerase Via Transcriptase Reversa , TransfecçãoRESUMO
Laryngeal carcinoma, as a malignant tumor that occurs in the head and neck region, is widely treated by radiation, but in some cases, the cancer is radioresistant to the radiotherapy. The reason for the radioresistant response needs to be clinically understood. We designed our present study to identify the molecules that may be involved in this radioresistant response. In this study, we initially established the inherent radioresistant (Hep-2max) and radiosensitive (Hep-2min) cell lines from the parental laryngeal cancer cell line Hep-2. Furthermore, using microarray analysis, we identified a novel inherent radioresistance-related gene, phosphoprotein associated with glycosphingolipid-enriched microdomains1 (PAG1). We showed that siRNA directed against PAG1 in a radioresistant (Hep-2max) cell line dramatically enhanced the radiosensitivity and IR-induced cell death. On the contrary, ectopic expression of PAG1 in radiosensitive (Hep-2min) cell lines led to radioresistance and suppressed the IR-induced cell death. Taken together, our results indicate that the PAG1 gene may be a novel, promising radiosensitization target for laryngeal carcinoma.
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Proteínas Adaptadoras de Transdução de Sinal/genética , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/radioterapia , Proteínas de Membrana/genética , Proteínas Adaptadoras de Transdução de Sinal/biossíntese , Morte Celular/efeitos da radiação , Linhagem Celular Tumoral , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Raios Infravermelhos , Neoplasias Laríngeas/metabolismo , Proteínas de Membrana/biossíntese , Análise de Sequência com Séries de Oligonucleotídeos , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/genética , Tolerância a Radiação/genética , TransfecçãoRESUMO
Theoretical estimates indicate that graphene thin films can be used as transparent electrodes for thin-film devices such as solar cells and organic light-emitting diodes, with an unmatched combination of sheet resistance and transparency. We demonstrate organic light-emitting diodes with solution-processed graphene thin film transparent conductive anodes. The graphene electrodes were deposited on quartz substrates by spin-coating of an aqueous dispersion of functionalized graphene, followed by a vacuum anneal step to reduce the sheet resistance. Small molecular weight organic materials and a metal cathode were directly deposited on the graphene anodes, resulting in devices with a performance comparable to control devices on indium-tin-oxide transparent anodes. The outcoupling efficiency of devices on graphene and indium-tin-oxide is nearly identical, in agreement with model predictions.