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1.
J Cancer Res Clin Oncol ; 150(4): 171, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38558328

RESUMO

BACKGROUND: Tryptophan (Trp) is an essential amino acid. Increasing evidence suggests that tryptophan metabolism plays a complex role in immune escape from Lung adenocarcinoma (LUAD). However, the role of long non-coding RNAs (lncRNAs) in tryptophan metabolism remains to be investigated. METHODS: This study uses The Cancer Genome Atlas (TCGA)-LUAD dataset as the training cohort, and several datasets from the Gene Expression Omnibus (GEO) database are merged into the validation cohort. Genes related to tryptophan metabolism were identified from the Molecular Signatures Database (MSigDB) database and further screened for lncRNAs with Trp-related expression. Subsequently, a prognostic signature of lncRNAs related to tryptophan metabolism was constructed using Cox regression analysis, (Least absolute shrinkage and selection operator regression) and LASSO analysis. The predictive performance of this risk score was validated by Kaplan-Meier (KM) survival analysis, (receiver operating characteristic) ROC curves, and nomograms. We also explored the differences in immune cell infiltration, immune cell function, tumor mutational load (TMB), tumor immune dysfunction and exclusion (TIDE), and anticancer drug sensitivity between high- and low-risk groups. Finally, we used real-time fluorescence quantitative PCR, CCK-8, colony formation, wound healing, transwell, flow cytometry, and nude mouse xenotransplantation models to elucidate the role of ZNF8-ERVK3-1 in LUAD. RESULTS: We constructed 16 tryptophan metabolism-associated lncRNA prognostic models in LUAD patients. The risk score could be used as an independent prognostic indicator for the prognosis of LUAD patients. Kaplan-Meier survival analysis, ROC curves, and risk maps validated the prognostic value of the risk score. The high-risk and low-risk groups showed significant differences in phenotypes, such as the percentage of immune cell infiltration, immune cell function, gene mutation frequency, and anticancer drug sensitivity. In addition, patients with high-risk scores had higher TMB and TIDE scores compared to patients with low-risk scores. Finally, we found that ZNF8-ERVK3-1 was highly expressed in LUAD tissues and cell lines. A series of in vitro experiments showed that knockdown of ZNF8-ERVK3-1 inhibited cell proliferation, migration, and invasion, leading to cell cycle arrest in the G0/G1 phase and increased apoptosis. In vivo experiments with xenografts have shown that knocking down ZNF8-ERVK3-1 can significantly inhibit tumor size and tumor proliferation. CONCLUSION: We constructed a new prognostic model for tryptophan metabolism-related lncRNA. The risk score was closely associated with common clinical features such as immune cell infiltration, immune-related function, TMB, and anticancer drug sensitivity. Knockdown of ZNF8-ERVK3-1 inhibited LUAD cell proliferation, migration, invasion, and G0/G1 phase blockade and promoted apoptosis.


Assuntos
Adenocarcinoma , Antineoplásicos , RNA Longo não Codificante , Animais , Camundongos , Humanos , RNA Longo não Codificante/genética , Triptofano/genética , Prognóstico , Imunidade , Fatores de Transcrição Kruppel-Like
2.
Microbiol Spectr ; : e0401223, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38497715

RESUMO

Esophageal squamous cell carcinoma (ESCC) is one of the most predominant subtypes of esophageal cancer. The characteristics of the gut microbiome and its metabolites from patients with ESCC have not been adequately studied and discussed. In this study, 40 fecal samples (20 from ESCC patients and 20 from healthy controls) were analyzed by 16S rRNA gene sequencing and untargeted metabolomics. The data sets were analyzed individually and synthesized using various bioinformatics methods. Alpha and beta diversity indicated significant differences in microbial diversity and abundance between ESCC and healthy control feces. At the genus level, the abundance of Phascolarctobacterium, Sutterella, and Streptococcus was significantly increased in ESCC. At the genus level, linear discriminant analysis effect size identified two biomarkers: Bacteroides_stercoris and Prevotella_copri. Untargeted metabolomics analysis revealed 307 differential metabolites between ESCC and healthy control feces, with indoles and derivatives, tropane alkaloids, lipids, and lipid-like molecules in higher relative abundance in ESCC feces than in healthy control feces. Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that unsaturated fatty acids (FAs), ascorbate and aldarate metabolism, and hypoxia-inducible factor 1 signaling pathway were significantly associated with differential metabolite. Phenylethanolamine and despropionyl p-fluoro fentanyl could be used as reliable biomarkers to differentiate ESCC from healthy control. The correlation analysis showed that Prevotella may be involved in the synthesis of fatty acyl, carboxylic acids and derivatives, benzenes and substituted derivatives, organic oxygenates, and indoles and derivatives as metabolites. Fusicatenibacter and Lachnospira may be involved in the degradation of indoles and derivatives. Alistipes, Agathobacter, and Parabacteroides may be involved in the synthesis of indoles and derivatives with strong contributions. There is an intricate relationship between the gut microbiome and the levels of several metabolites (e.g., fatty acyls, carboxylic acids and derivatives, indoles, and derivatives). Microbial-associated metabolites can be used as diagnostic biomarkers in therapeutic exploration. Further analysis revealed that Prevotella, Alistipes, Agathobacter, and Parabacteroides might promote ESCC by regulating the synthesis of indoles and their derivatives. The results of this study provide favorable evidence for the early diagnosis of ESCC and subsequent individualized treatment and targeted interventions.IMPORTANCEWe describe for the first time the differences in fecal microbiome composition and metabolites between patients with esophageal squamous cell carcinoma (ESCC) and healthy controls by 16S rRNA gene sequencing and untargeted metabolomics. The results of this study provide a favorable basis for the early diagnosis of ESCC and subsequent targeted interventional therapy.

4.
Support Care Cancer ; 31(12): 633, 2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37843658

RESUMO

PURPOSE: Nutritional management of patients with esophageal cancer is a significant issue. This systematic review aimed to comprehensively synthesize qualitative research evidence on the experiences and requirements in nutritional management from the perspective of patients with esophageal cancer. METHODS: A systematic review and meta-synthesis of qualitative studies were conducted. Studies written in Chinese or English were retrieved from nine databases, namely, PubMed, Web of Science, Cochrane Library, CINAHL, Embase, CNKI, WanFang, VIP, and SinoMed, from inception to December 23, 2022. After screening the titles, abstracts, and full texts, 19 articles were finally included for quality assessment and meta-synthesis. RESULTS: Three comprehensive themes were derived. These were dietary experiences (perception of symptoms and dietary behaviors), emotional experiences (negative and positive emotions), and social support (inappropriate social support and inadequate nutritional management). CONCLUSIONS: The experiences and requirements of esophageal cancer patients in terms of nutritional management during treatment and rehabilitation were reviewed and factors influencing nutritional management were discussed. The findings suggested that medical institutions should expedite the development of comprehensive nutritional management systems, create conducive nutritional environmental facilities, and establish interdisciplinary teams to implement personalized comprehensive interventional models for the management of patient nutrition. These steps would maximize the effectiveness of nutritional therapy, promote early patient recovery, and bridge the gap between healthcare professionals and patients in the understanding of nutritional management.


Assuntos
Neoplasias Esofágicas , Terapia Nutricional , Humanos , Apoio Social , Pessoal de Saúde , Estado Nutricional , Pesquisa Qualitativa
5.
BMC Cancer ; 23(1): 921, 2023 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-37773107

RESUMO

BACKGROUND: Phospholipase C Delta 3 (PLCD3) is a member of phospholipase C(PLC) Protein and PLCD3 protein plays a prominent role in many cancers. However, little is known about the role of PLCD3 in esophageal squamous cell carcinoma (ESCC). MATERIAL AND METHODS: We analyzed PLCD3 mRNA and protein expression in ESCC tissues and cell lines by immunohistochemistry, quantitative real-time PCR, and western blot. The correlation between PLCD3 expression and clinicopathological characteristics was also analyzed. CCK8, colony formation, wound-healing, and transwell assays were conducted to measure cell functional alternations. Flow cytometry was performed to assess the apoptosis rate and cell cycle caused by PLCD3 knockdown. Xenograft models in nude mice to clarify the role of PLCD3 in ESCC. Key proteins in the PI3K / AKT signaling pathway after treatment of ECA109 and KYSE150 cells with the AKT inhibitor MK2206 were analyzed by western blot. RESULTS: PLCD3 was highly expressed in ESCC tissues and cell lines. PLCD3 expression levels correlated with pathologic stage and lymphatic metastasis. PLCD3 knockdown inhibited cell proliferation, migration, invasion, promoted apoptosis, and caused the cell cycle arrest in the G1 phase. PLCD3 overexpression promoted cell proliferation, migration, and invasion. In vivo experiments with xenografts demonstrated that PLCD3 promoted ESCC tumorigenesis. Finally, Overexpression of PLCD3 activated the PI3K / AKT / P21 signaling. CONCLUSION: PLCD3 promotes malignant cell behaviors in esophageal squamous cell carcinoma via the PI3K/AKT/P21 signaling and could serve as a potential target for ESCC treatment.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Fosfolipase C delta , Animais , Humanos , Camundongos , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Camundongos Nus , Fosfatidilinositol 3-Quinases/metabolismo , Fosfolipase C delta/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/genética
7.
World J Surg Oncol ; 21(1): 155, 2023 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-37211596

RESUMO

OBJECTIVE: To investigate the predictive merit of combined preoperative nutritional condition and systemic inflammation on the prognosis of patients receiving esophagectomy, with the assessment of model construction to extract a multidisciplinary phantom having clinical relevance and suitability. METHODS: The software of R 4.1.2 was utilized to acquire the survival optimal truncation value and the confusion matrix of survival for the continuity variables. SPSS Statistics 26 was employed to analyze the correlation of parameters, where including t-test, ANOVA and the nonparametric rank sum test shall. Pearson chi-square test was used for categorical variables. The survival curve was retrieved by Kaplan-Meier method. Univariate analysis of overall survival (OS) was performed through log-rank test. Cox analysis was for survival analyze. The performance of the prediction phantom through the area under curve (AUC) of receiver operating characteristic curve (ROC), decision curve analysis (DCA), nomogram and clinical impact curve (CIC) was plotted by R. RESULTS: The AUC value of albumin-globulin score and skeletal muscle index (CAS) is markedly superior. Patients with diminished AGS and greater SMI were associated with improved overall survival (OS) and recurrence-free survival (RFS) (P < 0.01). The CAS composite evaluation model was calibrated with better accuracy and predictive performance. The DCA and CIC indicated a relatively higher net revenue for the prediction model. CONCLUSIONS: The prediction model including the CAS score has excellent accuracy, a high net revenue, and favorable prediction function.


Assuntos
Esofagectomia , Nomogramas , Humanos , Esofagectomia/efeitos adversos , Prognóstico , Inflamação
9.
Front Oncol ; 12: 1068198, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36568178

RESUMO

Background: Prediction of prognosis for patients with esophageal cancer(EC) is beneficial for their postoperative clinical decision-making. This study's goal was to create a dependable machine learning (ML) model for predicting the prognosis of patients with EC after surgery. Methods: The files of patients with esophageal squamous cell carcinoma (ESCC) of the thoracic segment from China who received radical surgery for EC were analyzed. The data were separated into training and test sets, and prognostic risk variables were identified in the training set using univariate and multifactor COX regression. Based on the screened features, training and validation of five ML models were carried out through nested cross-validation (nCV). The performance of each model was evaluated using Area under the curve (AUC), accuracy(ACC), and F1-Score, and the optimum model was chosen as the final model for risk stratification and survival analysis in order to build a valid model for predicting the prognosis of patients with EC after surgery. Results: This study enrolled 810 patients with thoracic ESCC. 6 variables were ultimately included for modeling. Five ML models were trained and validated. The XGBoost model was selected as the optimum for final modeling. The XGBoost model was trained, optimized, and tested (AUC = 0.855; 95% CI, 0.808-0.902). Patients were separated into three risk groups. Statistically significant differences (p < 0.001) were found among all three groups for both the training and test sets. Conclusions: A ML model that was highly practical and reliable for predicting the prognosis of patients with EC after surgery was established, and an application to facilitate clinical utility was developed.

10.
J Zhejiang Univ Sci B ; 23(11): 899-914, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36379610

RESUMO

OBJECTIVES: This study aimed to observe the clinical and immune response characteristics of vaccinated persons infected with the delta variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Yangzhou, China. METHODS: We extracted the medical data of 129 patients with delta-variant infection who were admitted to Northern Jiangsu People's Hospital (Yangzhou, China) between August and September, 2021. The patients were grouped according to the number of vaccine doses received into an unvaccinated group: a one-dose group and a two-dose group. The vaccine used was SARS-CoV-2-inactivated vaccine developed by Sinovac. We retrospectively analyzed the patients' epidemiological, clinical, laboratory, and imaging data. RESULTS: Almost all patients with delta-variant infection in Yangzhou were elderly, and patients with severe/critical illness were over 70 years of age. The rates of severe/critical illness (P=0.006), fever (P=0.025), and dyspnea (P=0.045) were lower in the two-dose group than in the unvaccinated group. Compared to the unvaccinated group, the two-dose group showed significantly higher lymphocyte counts and significantly lower levels of C-reactive protein (CRP), interleukin-6 (IL-6), and D-dimer during hospitalization and a significantly higher positive rate of immunoglobulin G (IgG) antibodies at admission (all P<0.05). The cumulative probabilities of hospital discharge and negative virus conversion were also higher in the two-dose group than in the unvaccinated group (P<0.05). CONCLUSIONS: Two doses of the SARS-CoV-2-inactivated vaccine were highly effective at limiting symptomatic disease and reducing immune response, while a single dose did not seem to be effective.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Idoso , Idoso de 80 Anos ou mais , Humanos , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Estado Terminal , Imunidade , Estudos Retrospectivos , SARS-CoV-2 , Vacinas de Produtos Inativados/efeitos adversos , Vacinas Virais/efeitos adversos
12.
Dis Esophagus ; 35(10)2022 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-35373248

RESUMO

BACKGROUND AND PURPOSE: This meta-analysis assesses the surgical outcomes between robot-assisted minimally-invasive McKeown esophagectomy and conventional one. METHOD: This meta-analysis searched the Web of Science, PUBMED, and EMBASE from the database's inception to January 2022. Altogether, 1073 records were identified in the literature search. Studies that evaluated the outcomes between robot-assisted minimally-invasive McKeown esophagectomy and conventional one among postoperative patients with oesophageal neoplasms were included. The assessed outcomes involved complications and clinical outcomes. In addition, heterogeneity was analyzed, and evidence quality was evaluated. RESULT: Evidence indicated that RAMIE (minimally-invasive esophagectomy assisted with robot) decreased incidences of lung complications and hospital stay as well as increased harvested lymph nodes. CONCLUSIONS: There was currently little evidence from randomized studies depicting that robot surgery manifested a clear overall advantage, but there was growing evidence regarding the clinical benefits of robot-assisted minimally invasive McKeown esophagectomy over conventional one.


Assuntos
Neoplasias Esofágicas , Procedimentos Cirúrgicos Robóticos , Robótica , Neoplasias Esofágicas/patologia , Esofagectomia/efeitos adversos , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Resultado do Tratamento
13.
Front Med (Lausanne) ; 9: 1030644, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36714109

RESUMO

We aimed to study the molecular mechanisms of chronic obstructive pulmonary disease (COPD) caused by cigarette smoke more comprehensively and systematically through different perspectives and aspects and to explore the role of protein acetylation modification in COPD. We established the COPD model by exposing C57BL/6J mice to cigarette smoke for 24 weeks, then analyzed the transcriptomics, proteomics, and acetylomics data of mouse lung tissue by RNA sequencing (RNA-seq) and liquid chromatography-tandem mass spectrometry (LC-MS/MS), and associated these omics data through unique algorithms. This study demonstrated that the differentially expressed proteins and acetylation modification in the lung tissue of COPD mice were co-enriched in pathways such as oxidative phosphorylation (OXPHOS) and fatty acid degradation. A total of 19 genes, namely, ENO3, PFKM, ALDOA, ACTN2, FGG, MYH1, MYH3, MYH8, MYL1, MYLPF, TTN, ACTA1, ATP2A1, CKM, CORO1A, EEF1A2, AKR1B8, MB, and STAT1, were significantly and differentially expressed at all the three levels of transcription, protein, and acetylation modification simultaneously. Then, we assessed the distribution and expression in different cell subpopulations of these 19 genes in the lung tissues of patients with COPD by analyzing data from single-cell RNA sequencing (scRNA-seq). Finally, we carried out the in vivo experimental verification using mouse lung tissue through quantitative real-time PCR (qRT-PCR), Western blotting (WB), immunofluorescence (IF), and immunoprecipitation (IP). The results showed that the differential acetylation modifications of mouse lung tissue are widely involved in cigarette smoke-induced COPD. ALDOA is significantly downregulated and hyperacetylated in the lung tissues of humans and mice with COPD, which might be a potential biomarker for the diagnosis and/or treatment of COPD.

14.
Zhongguo Fei Ai Za Zhi ; 24(7): 468-474, 2021 Jul 20.
Artigo em Chinês | MEDLINE | ID: mdl-34120430

RESUMO

BACKGROUND: The good prognosis of lepidic predominant invasive adenocarcinoma (LPA) and adenocarcinoma in situ (AIS)/microinvasive adenocarcinoma (MIA) in the pathological subtypes of early lung adenocarcinoma is similar, and the means to distinguish LPA from non-LPA is urgently needed in clinical practice. This study intends to analyze the correlation between positron emission computed tomography (PET)/computed tomography (CT) maximal standard uptake value (SUVmax) with CT three-dimensional reconstruction parameters and the pathological subtypes of early lung adenocarcinoma with part-solid nodules (PSNs) in preoperative imaging. METHODS: The data of early lung adenocarcinoma patients who underwent anatomical pneumonectomy at the Department of Thoracic Surgery of Northern Jiangsu People's Hospital from January 2016 to January 2019 retrospectively analyzed and subsolid nodules on imaging were showed. All patients with enhanced chest CT and PET/CT data can be obtained completely, using Mimics software to perform three-dimensional reconstruction to obtain tumor volume, 3-dimensional mean-CT value (3Dm-CT) of tumor and SUVmax, using SPSS 25.0 for statistical analysis and GraphPad Prism 8.3.0 for drawing receiver operating curve (ROC). P<0.05 indicates that the difference is statistically significant. RESULTS: 67 patients were included in this study. All patients were divided into two groups according to different pathological subtypes. AIS, MIA and LPA in invasive adenocarcinoma (IAC) were in the low-risk group, 28 cases (41.8%), and the remaining non-LPA were in high-risk group, 39 cases (58.2%). SUVmax (t=3.153, P=0.002), tumor volume (t=3.331, P=0.001), solid/ground glass component volume (t=2.74, P=0.006)/(t=3.127, P=0.002) and 3Dm-CT of solid/ground glass component (t=3.655, P<0.001)/(t=7.082, P<0.001) between the two groups were all statistically significant. ROC curve prompts: SUVmax [area under curve (AUC)=0.727], tumor volume (AUC=0.740), ground glass component volume (AUC=0.725), 3Dm-CT of solid components (AUC=0.763), 3Dm-CT of ground glass components (AUC=0.756) have the best predictive performance. The above-mentioned covariates with AUC>0.7 were included in the multivariate ROC curve analysis, and the joint predictor (AUC=0.835) was obtained with medium or above predictive value. CONCLUSIONS: PET/CT SUVmax and CT three-dimensional reconstruction parameters have a significant correlation with the different pathological subtypes of early lung adenocarcinoma with PSNs in imaging. The combination of SUVmax, tumor volume, ground glass component volume and 3Dm-CT of solid/ground glass component CT value has certain value in identifying the pathological subtype of early stage lung adenocarcinoma with PSNs nodules in imaging.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia Computadorizada por Raios X , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/cirurgia , Adulto , Idoso , Feminino , Humanos , Imageamento Tridimensional , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Pneumonectomia , Estudos Retrospectivos
15.
Cancer Biol Ther ; 22(4): 324-332, 2021 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-33970779

RESUMO

Evidence suggests that Tripartite Motif Containing 11 (TRIM11) has pro-tumor activity in human non-small cell lung cancer (NSCLC). However, the roles and underlying mechanisms of TRIM11 in NSCLC have not yet been fully elucidated. In this work, human lung cancer cell lines (A549, H446, and H1975) were transfected with siRNA or lentiviruses to knockdown or overexpress TRIM11 and dual-specificity phosphatase 6 (DUSP6). The cell tumor response was assessed by determining the rate of proliferation, apoptosis, the uptake of 2-[N-(7-nitrobenz-2-oxa-1, 3-diaxol-4-yl) amino]-2-deoxyglucose (2-NBDG), and the secretion of lactic acid (LD). Dominant-negative (dn)-MEK1 was used to block the ERK1/2 pathway. The mechanism was investigated by assessing the protein levels of pyruvate kinase isozymes M2 (PKM2) and DUSP6, as well as the activation of ERK1/2 pathway. Our data confirmed the anti-cancer effect of siTRIM11 in human lung cancer by demonstrating inhibition of cancer cell proliferation, induction of apoptosis, prevention of 2-NBDG uptake, suppression of LD production, and prevention of lung cancer cell (A549) tumorigenicity in nude mice. The underlying mechanism involved the up-regulation of DUSP6 and the inhibition of ERK1/2 activity. Overexpression of TRIM11 induced tumorigenesis of NSCLC in vitro, and the activation of ERK1/2 was significantly reversed by DUSP6 overexpression or additional dn-MEK1 treatment. Interestingly, we confirmed TRIM11 as a deubiquitinase that regulated DUSP6 accumulation, indicating that lung cancer progression is regulated via the DUSP6-ERK1/2 pathway. In conclusion, TRIM11 is an oncogene in NSCLC, likely through the DUSP6-mediated ERK1/2 signaling pathway.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Fosfatase 6 de Especificidade Dupla , Neoplasias Pulmonares , Proteínas com Motivo Tripartido , Células A549 , Animais , Carcinoma Pulmonar de Células não Pequenas/genética , Linhagem Celular Tumoral , Proliferação de Células , Fosfatase 6 de Especificidade Dupla/genética , Fosfatase 6 de Especificidade Dupla/metabolismo , Xenoenxertos , Humanos , Neoplasias Pulmonares/genética , Sistema de Sinalização das MAP Quinases , Camundongos , Camundongos Nus , Oncogenes , Transdução de Sinais , Proteínas com Motivo Tripartido/genética , Ubiquitina-Proteína Ligases/genética
16.
Oncol Rep ; 45(1): 359-367, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33416121

RESUMO

Long non­coding RNA Fer­1­like protein 4 (FER1L4) has been reported to play crucial regulatory roles in tumor progression and apoptosis. However, its clinical significance and biological role in non­small cell lung cancer (NSCLC) are completely unknown. The purpose of this study was to investigate the expression of lncRNA FER1L4 in plasma and tissues of patients with NSCLC and study the mechanism of proliferation and apoptosis of lung cancer cells. The expression levels of FER1L4 in plasma and tissues of NSCLC patients and cell lines were analyzed via RT­qPCR. The effects of FER1L4 on cell proliferation, migration and invasion were analyzed by CCK­8, wound healing and Transwell assays, respectively. The expression levels of related proteins were detected by western blot assay, while cell apoptosis was determined by Hoechst staining and flow cytometry. The results revealed that FER1L4 was significantly downregulated in NSCLC plasma and tissues and lung cancer cell lines compared to corresponding controls. Moreover, a significant decrease of cell proliferation, migration and invasion were observed in FER1L4­overexpressed cells. FER1L4 could promote phosphatase and tension homolog deleted on chromosome ten (PTEN) and p53 expression, inhibit AKT phosphorylation expression, thus increasing the proportion of apoptotic cells. The present study indicated that FER1L4 may inhibit cell proliferation and promote apoptosis of NSCLC cells via the PTEN/AKT/p53 pathway, which provides a better understanding of the pathogenesis of NSCLC and may provide a novel potential therapeutic target for clinical treatment.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , PTEN Fosfo-Hidrolase/genética , RNA Longo não Codificante/metabolismo , Adolescente , Adulto , Apoptose/genética , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação para Baixo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Pulmão/patologia , Pulmão/cirurgia , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , PTEN Fosfo-Hidrolase/metabolismo , Fosforilação/genética , Pneumonectomia , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/análise , RNA Longo não Codificante/genética , Transdução de Sinais/genética , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Adulto Jovem
17.
Cell Mol Biol (Noisy-le-grand) ; 66(7): 174-179, 2020 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-33287938

RESUMO

At present, in vitro cell experiments have confirmed that RaddeaninA can effectively inhibit the proliferation of some tumor cells, but the effect of RaddeaninA on lung cancer cells has not been observed. Therefore, this study explored its effect on lung cancer cells and its mechanism of action. Human lung cancer cell lines were treated with serum-free medium and varied concentrations of Raddeanin A. Cell proliferation and apoptosis were determined using MTT, and flow cytometric assays, respectively. The intracellular level of ROS was determined using DCFH-DA assay. Protein and mRNA expressions of bax, bcl-2 and cyt c were measured using Western blotting and qRT-PCR. RaddeaninA treatment can promote PC-9 cell apoptosis in a time and dose-dependent manner (p<0.05). Treatment of PC-9 cells with Raddeanin significantly and dose-dependently increased the activities of caspase-9 and caspase-3 (p<0.05), and led to significant and dose-dependent increases in ROS levels (p<0.05). Treatment of PC-9 cells with Raddeanin A led to significant and dose-dependent decreases in mitochondrial membrane potential (p<0.05). It significantly and dose-dependently upregulated bax mRNA and protein expressions, but down-regulated bcl-2 mRNA and protein expressions significantly and dose-dependently (p<0.05). On the other hand, Raddeanin significantly and dose-dependently down-regulated cytoplasmic bax protein expression, while upregulating cyt c expression (p<0.05). Similarly, bax protein expression was significantly and dose-dependently upregulated in mitochondria, but the corresponding cyt c expression was significantly and dose-dependently down-regulated (p<0.05). Raddeanin A is a potential and effective lung cancer chemotherapy drug, which can induce lung cancer cell apoptosis and inhibit proliferation.


Assuntos
Apoptose/efeitos dos fármacos , Neoplasias Pulmonares/patologia , Espécies Reativas de Oxigênio/metabolismo , Saponinas/farmacologia , Acetilcisteína/farmacologia , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Citocromos c/metabolismo , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Proteína X Associada a bcl-2/metabolismo
18.
J Clin Nurs ; 29(23-24): 4514-4531, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32869888

RESUMO

AIM: To explore nurses' experiences in natural disaster response. BACKGROUND: Nurses are key to disaster response. There is a growing body of qualitative research exploring this emerging nursing issue. However, there is a need to synthesise and summarise this body of knowledge to identify the overarching elements of how nurses experience working in disaster situations to reflect on their experiences so that we may help shape future clinical practice, research and education. DESIGN: Qualitative meta-synthesis. METHOD: Following PROSPERO guidelines (Moher et al., 2015), an exhaustive and systematic literature search and quality appraisal was undertaken in December 2019 to reveal nurses' experiences during natural disaster response. Sandelowski and Barroso's systematic retrieval, analysis and interpretation of findings method was used to produce a meta-summary of findings from 10 papers evaluating experiences across 9 disasters. A meta-aggregation was used to synthesise the findings from the studies and was methodically quality assessed with PRISMA and CASP. RESULTS: Our findings aggregated data from 42 sub-themes, into the following four themes to capture nurses' experiences after responding to disasters. These included agile response; leadership and innovative problem solving; building resilience; positive communication and need for psychological/emotional support. DISCUSSION: This meta-synthesis provides evidence to illustrate nurses' resilience and leadership capabilities as means to manage and perceive their disaster relief response. Factors such as emotional intelligence, capacity to react to changing situations, to manage scant resources in extreme situations were highlighted in nurses practising in highly stressful environments. Managers can use these examples to support ways to improve disaster management policies, but also, to engage in support for their staff. RELEVANCE TO CLINICAL PRACTICE: The role of nursing staff in disaster rescue is receiving significant attention. Understanding nurses' experiences during disaster rescue can help future leaders to improve capacity to respond and nursing preparedness through education, training and management, but also for continuing emotional support after the event.


Assuntos
Desastres Naturais , Recursos Humanos de Enfermagem , Humanos , Liderança , Pesquisa Qualitativa
19.
Zhongguo Fei Ai Za Zhi ; 22(11): 732-737, 2019 Nov 20.
Artigo em Chinês | MEDLINE | ID: mdl-31771744

RESUMO

BACKGROUND: The pathogenesis of a ciliated muconodular papillary tumor (CMPT) of the lung is extremely rare which is difficult to distinguish from other lung lesions and it is easy to cause misdiagnosis and missed diagnosis. By collecting CMPT data, its clinical and pathological features can provide medical treatment ideas for the majority of medical workers and reduce medical errors. METHODS: The clinical data, pathological features, immunophenotype of a typical CMPT patient and related literature were analyzed. RESULTS: The chest computed tomography (CT) showed there was a mixed density nodule in the right lower lung near the pleura with a diameter of about 9 mm. We performed a wedge resection on the patient. The pathological results showed that the nodule was composed of proliferated ciliated cells, mucous cells, and basal-like cells. The ciliated cells were lined on the surface of papillary structures. The basal-like cells were located in the outer layer, while the mucous cells were located between the two. The cell atypia was not obvious. Immunohistochemistry: epithelial cells CEA (+), CK7 (+), CA125 (+), weakly positive for TTF-1, CK20 (-), Ki67 (1%+), CK5/6 (+), and basal cells P63 (+). CONCLUSIONS: CMPT is a rare pulmonary neoplasm. There is no definite conclusion about its biologic nature, but most experts prefer a benign to a malignant tumor. CMPT can show many malignant tumor signs on imaging and is often mistaken for lung adenocarcinoma. According to its typical histopathological characteristics and immunohistochemical phenotype, it can be differentiated from other pulmonary diseases. Whether gene mutation is the driving factor is still unknown. Surgical resection for the tumor reveals a good prognosis.


Assuntos
Neoplasias Pulmonares/patologia , Humanos , Imunoquímica , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
20.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-749620

RESUMO

@#Esophageal carcinoma is one of the most common malignant tumor, a serious threat to human health. In the early and middle esophageal carcinoma patients, surgery is the only expected treatment to cure esophageal carcinoma. Traditional surgery of esophageal cancer needs thoracotomy and laparotomy, which has great trauma and high incidence of complications. So surgeons are looking for a minimally invasive surgical methods alternative to traditional esophagectomy. Video-mediastinoscopy is used to free middle and upper esophagus, as a minimally invasive surgical method, it is used in radical resection of esophageal cancer gradually. This article reviews the recent progress and the related research results in the application of mediastinoscopy in the radical resection of esophageal cancer. It is found that mediastinoscopy assisted the radical resection of esophageal cancer is a safe and feasible operation. It provides a feasible treatment option for early and middle stage esophageal cancer patients with pulmonary insufficiency who can not be resected by thoracoscopy.

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