RESUMO
Long noncoding RNAs (lncRNAs) contribute to esophageal squamous cell carcinoma (ESCC) progression, but the underlying mechanisms remain elusive. In this study, we verified a hitherto uncharacterized hypoxia-responsive lncRNA, G077640, which is upregulated in human ESCC cells and tissues, supporting the proliferation and migration of ESCC cells. Mechanistically, G077640 prevented hypoxia-inducible factor-1α (HIF1α) from being degraded by directly interacting with histone H2AX and further modulated the interaction of HIF1α and H2AX. In addition, G077640 reprogrammed glycolytic metabolism by regulating the expression of glucose transporter 4 (GLUT4), hexokinase 2 (HK2) and pyruvate dehydrogenase kinase 1 (PDK1) for ESCC proliferation and migration. Clinically, G077640 was associated with poor prognosis in ESCC patients. Taken together, our findings identified a hypoxia-responsive lncRNA that contributes to ESCC cells proliferation and migration, and targeting G077640 and its pathway might be a potential therapeutic strategy for ESCC.
Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , RNA Longo não Codificante , Humanos , Carcinoma de Células Escamosas do Esôfago/patologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias Esofágicas/patologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Linhagem Celular Tumoral , Carcinogênese/genética , Transformação Celular Neoplásica/genética , Hipóxia , Glicólise/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Movimento Celular/genéticaRESUMO
BACKGROUND: As an H3K27me3 demethylase and counteracts polycomb-mediated transcription repression, KDM6B has been implicated in the development and malignant progression in various types of cancers. However, its potential roles in esophageal squamous cell carcinoma (ESCC) have not been explored. METHODS: The expression of KDM6B in human ESCC tissues and cell lines was examined using RT-qPCR, immunohistochemical staining and immunoblotting. The effects of KDM6B on the proliferation and metastasis of ESCC were examined using in vitro and in vivo functional tests. RNA-seq and ChIP-seq assay were used to demonstrate the molecular biological mechanism of KDM6B in ESCC. RESULTS: We show that the expression level of KDM6B increased significantly in patients with lymph node metastasis. Furthermore, we confirmed that KDM6B knockdown reduces proliferation and metastasis of ESCC cells, while KDM6B overexpression has the opposite effects. Mechanistically, KDM6B regulates TNFA_SIGNALING_VIA_NFκB signalling pathways, and H3K27me3 binds to the promoter region of C/EBPß, leading to the promotion of C/EBPß transcription. Besides, we show that GSK-J4, a chemical inhibitor of KDM6B, markedly inhibits proliferation and metastasis of ESCC cells. CONCLUSIONS: The present study demonstrated that KDM6B promotes ESCC progression by increasing the transcriptional activity of C/EBPß depending on its H3K27 demethylase activity.
Assuntos
Proteína beta Intensificadora de Ligação a CCAAT/genética , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Regulação Neoplásica da Expressão Gênica/genética , Histona Desmetilases com o Domínio Jumonji/metabolismo , Animais , Benzazepinas/farmacologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Sequenciamento de Cromatina por Imunoprecipitação , Desmetilação do DNA , Conjuntos de Dados como Assunto , Progressão da Doença , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Histonas/metabolismo , Humanos , Histona Desmetilases com o Domínio Jumonji/antagonistas & inibidores , Histona Desmetilases com o Domínio Jumonji/genética , Masculino , Camundongos , Regiões Promotoras Genéticas , Pirimidinas/farmacologia , RNA-Seq , Ativação Transcricional , Regulação para Cima , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Tight junction is a structural constitution in cell-cell adhesion and play an important role in the maintenance of permeability and integrity of normal epithelial cell barrier. The protein encoded by Claudin 1 (CLDN1), a member of the claudin family, is an integral membrane protein and a component of tight junction strands. CLDN1 has been proved to regulate the proliferation and metastasis of multiple tumors, but little is known about its role in esophageal squamous cell carcinoma (ESCC). Here, we found that CLDN1 was aberrantly increased in ESCC tissues and cell lines, and mainly distributed in the nucleus of tumor cells. Furthermore, we confirmed that CLDN1 promoted the proliferation and metastasis of ESCC by triggering autophagy both in vitro and in vivo. Mechanically, we validated that CLDN1-induced autophagy via increasing Unc-51 like autophagy activating kinase 1 (ULK1) expression through AMP-activated protein kinase (AMPK)/signal transducer and activator of transcription 1 (STAT1) signaling pathway in ESCC cells. Taken together, our findings demonstrated that aberrant expression and distribution of CLDN1 promoted the proliferation and metastasis of esophageal squamous carcinoma by triggering autophagy through AMPK/STAT1/ULK1 signaling pathway.
Assuntos
Autofagia/genética , Proliferação de Células/genética , Claudina-1/genética , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Metástase Neoplásica/genética , Transdução de Sinais/genética , Proteínas Quinases Ativadas por AMP/genética , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/genética , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/patologia , Fator de Transcrição STAT1/genéticaRESUMO
OBJECTIVE: To determine the expression of tight junction protein CLDN1 in esophageal squamous carcinoma (ESCC) and to explore the effect of CLDN1 on the biological function of ESCC TE-11 cells. METHODS: This study collected 30 ESCC tissues,30 adjacent normal tissues and 30 distal esophageal tissues to detected the expression of CLDN1 in tissue microaary by immunohistochemistry method. Western blot was employed to determine the expression of CLDN1 in 15 ESCC tissues and cell lines,and then the distribution of CLDN1 in tumor cells and normal esophageal epithelial cells was analyzed. Lentivirus containing the sequence of CLDN1 shRNA was constructed and transfected into TE-11 cells,the transfection efficiency and intracellular distribution was determined by Western blot and flow cytometry. Cell proliferation was detected by CCK-8,the invasion and migration ability of cells was determined with Transwell. Cytoskeleton changes was observed by laser scanning confocal microscope. RESULTS: Immunohistochemical results showed no significant difference between the cancer tissues and adjacent tissues in term of the positive rate of CLDN1 ( P>0.05). CLDN1 was highly expressed in highly and moderately differentiated ESCC tissues,but its expression was significantly decreased in poorly differentiated cancer tissues. Western blot revealed that CLDN1 was mainly distributed in the nucleus of TE-11 cells. The proliferation of TE-11 cells,as well as invasion and migration ability,were declined obviously when the expression of CLDN1 being down-regulated,while the cytoskeleton protein fluorescence intensity deceased. CONCLUSION: The expression of CLDN1 in ESCC tissue is associated with its differentiation and may promote carcinogenesis in TE-11 cells.
Assuntos
Carcinoma de Células Escamosas/genética , Claudina-1/genética , Neoplasias Esofágicas/genética , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Invasividade Neoplásica , RNA Interferente Pequeno , TransfecçãoRESUMO
BACKGROUND: The use of MRI in isolated pediatric nystagmus remains a gray area in clinical management. Many clinicians prefer to order an MRI to rule out intracranial pathology despite the lack of clinically significant findings in most cases. OBJECTIVE: To assess the yield of MR imaging in isolated pediatric nystagmus and define a management algorithm to minimize avoidable MRI referrals and streamline MRI protocols. MATERIALS AND METHODS: We reviewed the charts of 148 children who underwent neuro MRI for isolated nystagmus between January 2008 and September 2014. We noted nystagmus onset and clinical characteristics and compared them with the MRI features and visual electrophysiology results. RESULTS: We included 85 boys and 63 girls (total 148, average age at MRI 4.24 ± 4.19 years). Twenty-three (15.5%) children had abnormal intracranial findings on MRI including abnormal signal lesions (4.1%; n=6), Chiari I malformations (3.4%; n=5) and optic pathway glioma (2.0%; n=3). The time of onset of nystagmus was not associated with an abnormal MRI (P=0.2). Seventy children underwent visual electrophysiology testing but this test could not predict abnormality at MRI, either (P=0.12). CONCLUSION: Among children with isolated nystagmus, 15.5% had abnormalities on neuroimaging. Neither clinical characteristics of nystagmus nor the visual electrophysiology results allowed prediction of intracranial pathology. We were unable to formulate a management algorithm for the optimal sequence of investigations (MRI preceding visual electrophysiology or vice versa), but we discuss the use of gadolinium contrast agent and orbital sequences in isolated pediatric nystagmus.
Assuntos
Imageamento por Ressonância Magnética/métodos , Nistagmo Patológico/diagnóstico por imagem , Adolescente , Criança , Pré-Escolar , Olho/diagnóstico por imagem , Feminino , Humanos , Lactente , Masculino , Estudos RetrospectivosRESUMO
Recent single-arm studies involving neoadjuvant camrelizumab, a PD-1 inhibitor, plus chemotherapy for resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC) have shown promising results. This multicenter, randomized, open-label phase 3 trial aimed to further assess the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy followed by adjuvant camrelizumab, compared to neoadjuvant chemotherapy alone. A total of 391 patients with resectable thoracic LA-ESCC (T1b-3N1-3M0 or T3N0M0) were stratified by clinical stage (I/II, III or IVA) and randomized in a 1:1:1 ratio to undergo two cycles of neoadjuvant therapy. Treatments included camrelizumab, albumin-bound paclitaxel and cisplatin (Cam+nab-TP group; n = 132); camrelizumab, paclitaxel and cisplatin (Cam+TP group; n = 130); and paclitaxel with cisplatin (TP group; n = 129), followed by surgical resection. Both the Cam+nab-TP and Cam+TP groups also received adjuvant camrelizumab. The dual primary endpoints were the rate of pathological complete response (pCR), as evaluated by a blind independent review committee, and event-free survival (EFS), as assessed by investigators. This study reports the final analysis of pCR rates. In the intention-to-treat population, the Cam+nab-TP and Cam+TP groups exhibited significantly higher pCR rates of 28.0% and 15.4%, respectively, compared to 4.7% in the TP group (Cam+nab-TP versus TP: difference 23.5%, 95% confidence interval (CI) 15.1-32.0, P < 0.0001; Cam+TP versus TP: difference 10.9%, 95% CI 3.7-18.1, P = 0.0034). The study met its primary endpoint of pCR; however, EFS is not yet mature. The incidence of grade ≥3 treatment-related adverse events during neoadjuvant treatment was 34.1% for the Cam+nab-TP group, 29.2% for the Cam+TP group and 28.8% for the TP group; the postoperative complication rates were 34.2%, 38.8% and 32.0%, respectively. Neoadjuvant camrelizumab plus chemotherapy demonstrated superior pCR rates compared to chemotherapy alone for LA-ESCC, with a tolerable safety profile. Chinese Clinical Trial Registry identifier: ChiCTR2000040034 .
RESUMO
BACKGROUND: As a new surgical procedure for non-small cell lung cancer, single-port video-assisted thoracoscopic surgery (VATS) has lately gained popularity; nevertheless, it is unknown if single-port VATS offers any advantages over multi-portal. The study aims to assess the different impacts of using single-port VATS versus 2-port or multi-port VATS such as operation and drainage time, blood loss volume, number of resected lymph nodes, and hospital stay in lung cancer patients. METHODS: Inclusion criteria included studies from different languages that compare single-port against 2 or multi-port VATS. The outcomes of these studies were analyzed using a random-effect model and it was used to calculate the mean difference with 95 percent confidence intervals to quantify the impact of different surgical techniques on clinical parameters. RESULTS: Single or Uni-portal video-assisted thoracoscopic surgery results in significantly lower drainage time after surgery compared with 2-port (P = .03) and multi-port (P < .001) VATS. In contrast to the resection of lymph nodes, there was no significant difference between uni-port and 2-port (P = .49) or multiport (P = .29) VATS. While operation time, blood loss, complications, and hospital stay were significantly lower in uni-port compared with multi-port VATS (P = .04, P = .002, P < .001, respectively), but not with 2-port VATS (P = .44, 0.06, P = .13). There were no significant differences between uni-port and multi-port VATS regarding conversion rate, mortality, and staging. CONCLUSION: Single or Uni-portal video-assisted thoracoscopic surgery has high efficacy and lower side effects compared with multi-port regarding the perioperative outcomes. Two-port VATS has similar results with uni-port in several parameters.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/etiologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Cirurgia Torácica Vídeoassistida/métodos , Pneumonectomia/métodos , PulmãoRESUMO
Cartilage has a limited self-repair capability and the repair of large cartilage defects remains a challenge in clinic. This study aimed to investigate the effect of mesenchymal stem cells (MSCs) loaded three-dimensional bilayer collagen scaffold for cartilage repair. Cross-linked three-dimensional bilayer collagen scaffolds seeded with or without MSCs were implanted into large cartilage defects (4 mm in diameter; 3 mm in depth) in rabbit knees. The untreated cartilage defects served as control. The tissue response was evaluated at 6 and 12 weeks after implantation by general histology and semi-quantitative histological grading systems. In addition, the repaired tissues were evaluated by mechanical test at 12 weeks after implantation. The MSCs-loaded collagen scaffold group showed the most hyaline cartilage, highest histological scores and compressive modulus. Moreover, it showed a good integration with the subchondral bone and adjacent cartilage. The structure of the novel bilayer collagen scaffolds provided architectural support for the differentiation of MSCs and demonstrated successful induction of in vivo chondrogenesis. These findings suggested that MSCs-loaded bilayer collagen scaffold could be an appealing candidate to be used for cartilage regeneration.
Assuntos
Cartilagem Articular/lesões , Cartilagem Articular/fisiologia , Regeneração Tecidual Guiada/métodos , Transplante de Células-Tronco Mesenquimais/métodos , Engenharia Tecidual/métodos , Alicerces Teciduais , Análise de Variância , Animais , Diferenciação Celular/fisiologia , Colágeno/metabolismo , Técnicas Histológicas , Masculino , Coelhos , Estresse Mecânico , Resultado do TratamentoRESUMO
Purpose: Accurate clinical staging is crucial to managing esophageal cancer. [68Ga]Ga-DOTA-FAPI-04 exhibits good diagnostic performance in various tumors, showing a promising alternative to [18F]FDG. Here, we investigated the diagnostic performance of [68Ga]Ga-DOTA-FAPI-04 PET/CT and [18F]FDG PET/CT in the diagnosis of primary and metastatic lesions of esophageal cancer. Methods: Patients with esophageal cancer who underwent concurrent [68Ga]Ga-DOTA-FAPI-04 and [18F]FDG PET/CT between January 2020 and June 2021 were retrospectively analyzed. [68Ga]Ga-DOTA-FAPI-04 and [18F]FDG PET/CT uptakes were compared by using the paired samples t test. The McNemar test was used to compare the diagnostic performance between the two techniques. Results: Thirty-five patients (ranging from 44-83 years old with a median age of 63.5 years) were evaluated in our study. In treatment-naive patients (n=25), [68Ga]Ga-DOTA-FAPI-04 PET could detect all esophageal cancers, whereas 1 patient with superficial esophageal cancer was negative in FDG but positive in [68Ga]Ga-DOTA-FAPI-04 (T1). [68Ga]Ga-DOTA-FAPI-04 uptake was higher than [18F]FDG in primary lesions (13.8 ± 6.9 vs 10.9 ± 6.8, respectively, P=0.004), involved lymph nodes (9.3 ± 5.2 vs 6.4 ± 5.9, respectively, P=0.002), and bone and visceral metastases (10.4 ± 6.0 vs 6.1 ± 7.5, respectively, P=0.001). In addition, [68Ga]Ga-DOTA-FAPI-04 PET/CT has a higher detection sensitivity than [18F]FDG PET/CT for primary tumors [100% (25/25) vs. 96.0% (24/25), respectively], lymph nodes [95.0% (57/60) vs 75.0% (45/60), P<0.001], and bone and visceral metastases [100% (25/25) vs 72% (18/25), respectively; P= 0.008]. Conclusion: [68Ga]Ga-DOTA-FAPI-04 PET/CT has higher tracer uptake value and is superior to [18F]FDG PET/CT in detecting primary and metastatic lesions in patients with esophageal cancer.
RESUMO
Platinum-based chemotherapy is the standard first-line treatment for advanced esophageal squamous cell carcinoma (ESCC). In this phase 3 study (ClinicalTrial.gov: NCT03829969), 514 patients with treatment-naïve advanced ESCC were randomized (1:1) to receive toripalimab or placebo in combination with paclitaxel plus cisplatin (TP) every 3 weeks for up to 6 cycles, followed by toripalimab or placebo maintenance. At the prespecified final analysis of progression-free survival (PFS), a significant improvement in PFS is observed for the toripalimab arm over the placebo arm (hazard ratio [HR] = 0.58; 95% CI, 0.46-0.74; p < 0.0001). The prespecified interim analysis of overall survival (OS) also reveals a significant OS improvement for patients treated with toripalimab plus TP over placebo plus TP (HR = 0.58; 95% CI, 0.43-0.78; p = 0.0004). The incidences of grade ≥3 treatment-emergent adverse events are similar between the two arms. Toripalimab plus TP significantly improves PFS and OS in patients with treatment-naïve, advanced ESCC, with a manageable safety profile.
Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Esofágicas/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Humanos , Intervalo Livre de ProgressãoRESUMO
BACKGROUND: Immune-related genes (IRGs) are highly relevant to the progression and prognosis of esophageal squamous cell carcinoma (ESCC). A prognostic signature could be reliable in stratifying ESCC patients according to the risk score, which may help manage systematic treatments. In this study, a systematic and reliable immune signature was developed to estimate the prognostic stratification in ESCC. METHODS: Ribonucleic acid (RNA) expression data of 79 ESCC samples from the Cancer Genome Atlas (TCGA) database and 269 normal esophageal mucosal samples from the Genotype-Tissue Expression (GTEx) project database were downloaded from the University of California, Santa Cruz (UCSC) website to form a TCGA-GTEx dataset. First, we screened differentially expressed genes (DEGs) and then filtered IRGs based on the Immunology Database and Analysis Portal (ImmPort) database to obtain immune-related DEGs (IRDEGs). Next, a novel prognostic signature based on IRDEGs was developed using multivariable Cox analysis. Immune infiltration status was evaluated via single-sample gene set enrichment analysis (ssGSEA). ESCC tissues were grouped into three clusters in terms of immune infiltration (Immunity-L, Immunity-M, and Immunity-H) by applying an unsupervised hierarchical clustering algorithm. Finally, the samples were divided into high- and low-risk groups using the median of the risk score scores for GSEA pathway enrichment analysis in the three clusters. RESULTS: The prognostic signature based on IRDEGs (FCER1G, ISG20, and EGFR) performed moderately in prognostic predictions, with a concordance index (C-index) value of 0.73 [95% (confidence interval) CI: 0.63-0.84, P=2.02E-05] and an area under the curve (AUC) value of 0.817. The xenobiotic metabolism pathway was significantly enriched and up-regulated both in the high-risk group of the immunity-M and immunity-H clusters. CONCLUSIONS: The novel immune-related prognostic signature we constructed has a good prognostic, predictive ability and can be used as an independent prognostic indicator. Our study provides clinicians with a quantitative tool to predict the probability of individual survival time and helps clinicians select targets for immunotherapies and individualized treatment strategies for ESCC patients.
RESUMO
BACKGROUND: The therapeutic response and prognosis of patients with non-small cell lung carcinoma (NSCLC) are widely related to immunity. To improve the prognosis of patients and provide reliable information to guide appropriate personalized treatment strategies, it is necessary to identify reliable prognostic or predictive indicators closely related to tumor phenotype and immune traits in NSCLC. METHODS: Based on The Cancer Genome Atlas (TCGA)-NSCLC mRNA expression profile data, a novel approach combining differential gene expression analysis, single-sample gene set enrichment analysis (ssGSEA), and weighted gene co-expression network analysis (WGCNA) was used to screen hub genes. Subsequently, the regulator of hemoglobinization and erythroid cell expansion (RHEX) was identified as a key gene using the log-rank test and confirmed in the ArrayExpress database. The relationship between RHEX and clinicopathological parameters was analyzed using the Wilcoxon rank-sum test. More importantly, through gene set enrichment analysis (GSEA) and cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) algorithms, and with reference to the Tumor IMmune Estimation Resource (TIMER) database, we explored the relevant pathways of RHEX and its relationship with tumor-infiltrating immune cells (TICs). Finally, we depicted the association between RHEX and immunomodulators in the TCGA and a web portal TISIDB. RESULTS: The RHEX mRNA expression levels in tumor tissues were lower than those in normal tissues and declined with the progression of NSCLC. Meanwhile, RHEX overexpression was associated with high immune infiltration levels and a favorable clinical prognosis. RHEX may participate in tumor microenvironment (TME) regulation through multiple tumor-immune related pathways, especially the JAK-STAT signaling pathway. Furthermore, RHEX expression affected the infiltrating abundance of multiple TICs and positively correlated with most of the immunomodulators in NSCLC. CONCLUSIONS: Our study is the first to propose that RHEX is an immune-related gene with prognostic value in NSCLC and reveals the underlying mechanism between RHEX and tumor-immune system interactions. These results ultimately provide guidance for prognosis and immunotherapy for NSCLC patients.
RESUMO
Diphenhydramine (DPH) is an over-the-counter antihistamine medication commonly used for symptom management in palliative care. Despite the ease of access and perceived safety of DPH, there is documented evidence of potential for abuse of this medication. We present a case of a 61-year-old man with metastatic carcinoma of the distal esophagus, who was initially admitted with a pain crisis but subsequently developed a severe DPH withdrawal syndrome consisting of hyperactive delirium, autonomic dysfunction, and increased muscle tone. With careful selection of the antipsychotic agent loxapine, additional symptom management medications and scheduled tapering the patient was able to be discharged home for end-of-life care. We highlight the challenges of recognizing and managing a withdrawal syndrome in patients with terminal illnesses at end of life.
Assuntos
Antipsicóticos , Enfermagem de Cuidados Paliativos na Terminalidade da Vida , Difenidramina/uso terapêutico , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados PaliativosRESUMO
BACKGROUND: The SVV tests the ability of a person to perceive the gravitational vertical. A tilt in SVV indicates vestibular imbalance in the roll plane, and thus injuries to the utricle or its connecting nerves. A validated bedside method (et, al., 2009, 72(19):1689-1692, Neurol, Zwergal) is the bucket method, in which the subject estimates the true vertical by attempting to properly align a straight line visible on the bottom of a bucket that is rotated at random by the examiner. In our study, the subjects need to align the plumb line on the Visual Vertical iOS app to the vertical direction. METHODS: Measurements of the SVV were made in 22 healthy subjects (16 females and 6 males). Each subject conducted 10 iterations of bucket test and 10 iterations of iOS app test. The reliability and validity of the iOS app was analyzed by SPSS21. RESULTS: Cronbach's α for the plumb line method was 0.976, and the iOS app was 0.978. Statistical comparison of SVV values measured by the iOS app and the bucket method showed no significant difference in distribution (Mann Whitney U test U = 0.944). CONCLUSION: The Visual Vertical iOS app is an effective and accessible substitute to the plumb line for the measurement of the validated bucket test.
Assuntos
Aplicativos Móveis , Testes de Função Vestibular/métodos , Adulto , Feminino , Voluntários Saudáveis , Humanos , Masculino , Reprodutibilidade dos TestesRESUMO
PURPOSE OF REVIEW: An increasing number of patients are turning to cannabis and cannabinoids for management of their palliative and nonpalliative cancer pain and other cancer-related symptoms. Canadians have a legal framework for access to medical cannabis, which provides a unique perspective in a setting lacking robust clinical evidence. This review seeks to delineate the role of cannabis and cannabinoids in cancer pain management and offers insight into the Canadian practice. RECENT FINDINGS: A cohort study using nabiximols on advanced cancer pain in patients already optimized on opioids, over 3 weeks, demonstrated improved average pain score. A large observational study of cancer patients using cannabis over 6 months demonstrated a decreased number of patients with severe pain and decreased opioid use, whereas the number of patients reporting good quality of life increased. SUMMARY: Good preclinical animal data and a large body of observational evidence point to the potential efficacy of cannabinoids for cancer pain management. However, there are relatively weak data pointing to clinical efficacy from clinical trial data to date. In Canada, the burgeoning cannabis industry has driven the population to embrace a medicine before clinical evidence. There remains a need for high-quality randomized controlled trials to properly assess the effectiveness and safety of medical cannabis, compared with placebo and standard treatments for cancer-related symptoms.
Assuntos
Dor do Câncer/tratamento farmacológico , Maconha Medicinal/uso terapêutico , Manejo da Dor/métodos , Cuidados Paliativos/métodos , Analgésicos Opioides/uso terapêutico , Canadá , Canabidiol/uso terapêutico , Dor Crônica/tratamento farmacológico , Ensaios Clínicos como Assunto , Dronabinol/uso terapêutico , Combinação de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Humanos , Maconha Medicinal/administração & dosagem , Maconha Medicinal/efeitos adversos , Qualidade de Vida , Índice de Gravidade de DoençaRESUMO
PURPOSE: MiR-654-3p plays important roles in many types of malignant tumours. However, the biological function of miR-654-3p in non-small cell lung cancer (NSCLC) remains unknown. In this study, the role of miR-654-3p in NSCLC was investigated. METHODS: qRT-PCR was used to evaluate the level of miR-654-3p in NSCLC tissues and cell lines, while Cell Counting Kit-8, Annexin V/propidium iodide dual staining or TUNEL staining were used to investigate proliferation and apoptosis of NSCLC cells. Luciferase assays and Western blotting were performed to validate potential targets of miR-654-3p. RESULTS: MiR-654-3p levels were significantly decreased in NSCLC patients and cell lines and were significantly correlated with the tumour size and tumour node metastasis stage of NSCLC patients. In A549 cells, miR-654-3p overexpression significantly increased apoptosis and inhibited growth both in vivo and in vitro, while downregulation of miR-654-3p had the opposite effects. In addition, polo-like kinase 4 (PLK4) was shown to be a target gene of miR-654-3p that is negatively regulated by miR-654-3p in A549 cells. Furthermore, PLK4 was observed to be highly expressed in NSCLC tissues and cells, and PLK4 overexpression abolished the inhibitory effects of miR-654-3p overexpression on NSCLC cell proliferation. Finally, the animal experiment results further demonstrated that miR-654-3p inhibits tumour growth and regulates PLK4 expression. CONCLUSION: Our results demonstrate that miR-654-3p functions as a growth-suppressing miRNA by targeting PLK4 in NSCLC.
RESUMO
BACKGROUND: Recurrence and metastasis are the leading causes of tumour-related death in patients with oesophageal squamous cell carcinoma (ESCC). Tumour-infiltrating natural killer cells (NK cells) display powerful cytotoxicity to tumour cells and play a pivotal role in tumour therapy. However, the phenotype and functional regulation of NK cells in oesophageal squamous cell carcinoma (ESCC) remains largely unknown. METHODS: Single cell suspensions from blood and tissue samples were isolated by physical dissociation and filtering through a 70 µm cell strainer. Flow cytometry was applied to profile the activity and function of NK cells, and an antibody chip experiment was used to identify and quantitate cytokine levels. We studied IL-6 and IL-8 function in primary oesophageal squamous carcinoma and NK cell co-cultures in vitro and by a xenograft tumour model in vivo. Western blotting was used to quantitate STAT3 (signal transducer and activator of transcription 3) and p-STAT3 levels. Finally, we performed an IHC array to analyse IL-6/IL-8 (interleukin 6/interleukin 8) expression in 103 pairs of tumours and matched adjacent tissues of patients with ESCC to elucidate the correlation between IL-6 or IL-8 and clinical characteristics. RESULTS: The percentages of NK cells in both peripheral blood and tumour tissues from patients with ESCC were significantly increased in comparison with those in the controls and correlated with the clinical characteristics. Furthermore, the decrease in activating receptors and increase in inhibitory receptors on the surface of tumour-infiltrating NK cells was confirmed by flow cytometry. The level of granzyme B, the effector molecule of tumour-infiltrating NK cells, was also decreased. Mechanistically, primary ESCC cells activated the STAT3 signalling pathway on NK cells through IL-6 and IL-8 secretion, leading to the downregulation of activating receptors (NKp30 and NKG2D) on the surface of NK cells. An ex vivo study showed that blockade of STAT3 attenuated the IL-6/IL-8-mediated impairment of NK cell function. Moreover, the expression of IL-6 or IL-8 in tumour tissues was validated by immunohistochemistry to be positively correlated with tumour progression and poor survival, respectively. CONCLUSIONS: Tumour cell-secreted IL-6 and IL-8 impair the activity and function of NK cells via STAT3 signalling and contribute to oesophageal squamous cell carcinoma malignancy.
Assuntos
Carcinoma de Células Escamosas do Esôfago/genética , Interleucina-6/genética , Interleucina-8/genética , Fator de Transcrição STAT3/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Linhagem Celular Tumoral , Proliferação de Células/genética , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/patologia , Masculino , Camundongos , Pessoa de Meia-Idade , Metástase Neoplásica , Transdução de Sinais/genética , Análise de Célula Única , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Propofol and midazolam are widely used for the sedation of bronchoscopy. This systematic review and meta-analysis is conducted to compare the efficacy of propofol and midazolam for bronchoscopy. METHODS: The databases including PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases are systematically searched for collecting the randomized controlled trials (RCTs) regarding the efficacy of propofol and midazolam for bronchoscopy. RESULTS: This meta-analysis has included 4 RCTs. Compared with midazolam intervention in patients undergoing bronchoscopy, propofol intervention is associated with remarkably reduced recovery time [standard mean difference (SMD)â=â-0.74; 95% confidence interval (95% CI)â=â-1.04 to -0.45; Pâ<â.00001], but demonstrates no significant impact on operation time (SMDâ=â-0.01; 95% CIâ=â-0.16 to 0.13; Pâ=â.87), induction time (SMDâ=â-0.58; 95% CIâ=â-1.19 to 0.03; Pâ=â.06), lowest oxyhemoglobin saturation (SpO2, SMDâ=â0.24; 95% CIâ=â-0.09 to 0.58; Pâ=â.15), SpO2 <90% [risk ratio (RR)â=â1.02; 95% CIâ=â0.82-1.25; Pâ=â.88), and major arrhythmias (RRâ=â0.56; 95% CIâ=â0.26-1.19; Pâ=â.13). CONCLUSION: Propofol sedation is able to reduce recovery time and shows similar safety compared with midazolam sedation during bronchoscopy.