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Aquaporin 3 (AQP3), which is mostly expressed in pulmonary epithelial cells, was linked to lung adenocarcinoma (LUAD). However, the underlying functions and mechanisms of AQP3 in the tumor microenvironment (TME) of LUAD have not been elucidated. Single-cell RNA sequencing (scRNA-seq) was used to study the composition, lineage, and functional states of TME-infiltrating immune cells and discover AQP3-expressing subpopulations in five LUAD patients. Then the identifications of its function on TME were examined in vitro and in vivo. AQP3 was associated with TNM stages and lymph node metastasis of LUAD patients. We classified inter- and intra-tumor diversity of LUAD into twelve subpopulations using scRNA-seq analyses. The analysis showed AQP3 was mainly enriched in subpopulations of M2 macrophages. Importantly, mechanistic investigations indicated that AQP3 promoted M2 macrophage polarization by the PPAR-γ/NF-κB axis, which affected tumor growth and migration via modulating IL-6 production. Mixed subcutaneous transplanted tumor mice and Aqp3 knockout mice models were further utilized, and revealed that AQP3 played a critical role in mediating M2 macrophage polarization, modulating glucose metabolism in tumors, and regulating both upstream and downstream pathways. Overall, our study demonstrated that AQP3 could regulate the proliferation, migration, and glycometabolism of tumor cells by modulating M2 macrophages polarization through the PPAR-γ/NF-κB axis and IL-6/IL-6R signaling pathway, providing new insight into the early detection and potential therapeutic target of LUAD.
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Adenocarcinoma del Pulmón , Acuaporina 3 , Interleucina-6 , Neoplasias Pulmonares , Macrófagos , FN-kappa B , PPAR gamma , Acuaporina 3/metabolismo , Acuaporina 3/genética , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/metabolismo , Adenocarcinoma del Pulmón/genética , Animales , Interleucina-6/metabolismo , Humanos , PPAR gamma/metabolismo , Macrófagos/metabolismo , Ratones , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/genética , FN-kappa B/metabolismo , Microambiente Tumoral , Progresión de la Enfermedad , Regulación hacia Arriba , Masculino , Transducción de Señal , Línea Celular Tumoral , Ratones Noqueados , Ratones Endogámicos C57BL , FemeninoRESUMEN
BACKGROUND: Current evidence provides limited support for the superiority of endovascular thrombectomy (EVT) in patients with M2 segment middle cerebral artery occlusion. We aim to investigate whether imaging features of M2 segment occlusion impact the effectiveness of EVT. METHODS: We conducted a retrospective cohort study from January 2017 to January 2022, drawing data from the CASE II registry (Computer-Based Online Database of Acute Stroke Patients for Stroke Management Quality Evaluation), which specifically documented patients with acute ischemic stroke presenting with M2 segment occlusion undergoing reperfusion therapy. Patients were stratified into the intravenous thrombolysis (IVT) group (IVT alone) and EVT group (IVT plus EVT or EVT alone). The primary outcome was a modified Rankin Scale score 0 to 2 at 90 days. Secondary outcomes included additional thresholds and distribution of modified Rankin Scale scores, 24-hour recanalization, early neurological deterioration, and relevant complications during hospitalization. Safety outcomes encompassed intracranial hemorrhagic events at 24 hours and mortality at 90 days. Binary logistic regression analyses with propensity score matching were used. Subgroup analyses were performed based on the anatomic site of occlusion, including right versus left, proximal versus distal, dominant/co-dominant versus nondominant, single versus double/triple branch(es), and anterior versus central/posterior branch. RESULTS: Among 734 patients (43.3% were females; median age, 73 years) with M2 segment occlusion, 342 (46.6%) were in the EVT group. Propensity score matching analysis revealed no statistical difference in the primary outcome (odds ratio, 0.860 [95% CI, 0.611-1.209]; P=0.385) between the EVT group and IVT group. However, EVT was associated with a higher incidence of subarachnoid hemorrhage (odds ratio, 6.655 [95% CI, 1.487-29.788]; P=0.004) and pneumonia (odds ratio, 2.015 [95% CI, 1.364-2.977]; P<0.001). Subgroup analyses indicated that patients in the IVT group achieved better outcomes when presenting with right, distal, or nondominant branch occlusion (Pall interaction<0.05). CONCLUSIONS: Our study showed similar efficiency of EVT versus IVT alone in acute M2 segment middle cerebral artery occlusion. This suggested that only specific patient subpopulations might have a potentially higher benefit of EVT over IVT alone. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT04487340.
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Infarto de la Arteria Cerebral Media , Trombectomía , Terapia Trombolítica , Humanos , Masculino , Femenino , Trombectomía/métodos , Anciano , Infarto de la Arteria Cerebral Media/cirugía , Terapia Trombolítica/métodos , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Anciano de 80 o más Años , Procedimientos Endovasculares/métodos , Sistema de Registros , Accidente Cerebrovascular Isquémico/cirugía , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/terapiaRESUMEN
Background: Detection rate and isolation yield of circulating tumor cells (CTCs) are low in lung cancer with approaches due to CTC invasiveness and heterogeneity. In this study, on the basis of the epithelial cell adhesion molecule (EpCAM) phenotype, markers of vimentin and epidermal growth factor receptor (EGFR) phenotype were added to jointly construct a precise and efficient CTC capture system for capture of lung cancer CTCs. Methods: A CTC capture system combined with EpCAM lipid magnetic bead (Ep-LMB)/vimentin lipid magnetic bead (Vi-LMB)/EGFR lipid magnetic bead (EG-LMB) was constructed, and its performance was tested. The amount of CTC captured in the blood of patients with lung cancer was detected by immunofluorescence identification and analyzed for clinical relevance. Results: The constructed CTC capture system has low cytotoxicity. The capture efficiency of lung cancer cells in phosphate belanced solution (PBS) system was 95.48%. The capture efficiency in the blood simulation system is 94.55%. The average number of CTCs in the blood of patients with lung cancer was 9.73/2 mL. The quantity distribution of CTCs is significantly correlated with tumor staging and metastasis. The area under the curve (AUC) of CTCs for the diagnosis of lung cancer was 0.9994 (95% CI = 0.9981-1.000, P < .0001). The cutoff value was 4.5/2 mL. The sensitivity was 99.39%, and the specificity was 96.88%. Conclusion: The EpCAM/vimentin/EGFR combined capture system has feasibility and high sensitivity in the detection of lung cancer CTC typing, which can be used as an auxiliary diagnostic indicator for lung cancer and is expected to promote the clinical application of CTCs.
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Background: Lung adenocarcinoma (LUAD) incidence and mortality take the leading place of most malignancies. Previous studies have revealed the regulator of chromosome condensation 1 (RCC1) family members played an essential role during tumorigenesis. However, its biological functions in LUAD still need further investigation. Methods: Several databases were applied to explore potential effects of RCC1 family members on LUAD, such as Oncomine, GEPIA, and cBioPortal. Real-time PCR and immunohistochemistry were used to verify the expression of RCC2 in stage I LUAD. H1975 and A549 were selected to explore the biological function of RCC2 in cellular malignant phenotype. Results: The expressions of RCC1 and RCC2 showed marked differences in malignant tissue compared to lung tissue. The higher the expression levels of RCC1 or RCC2 in LUAD patients, the shorter their overall survival (OS). In normal lung tissues, RCC1 expression was highly enriched in alveolar cells and endothelial cells. Compare with RCC1, RCC2 expression in normal lung tissue was significantly enriched in macrophages, B cells and granulocytes. Additionally, RCC2 expression level was correlated with multiple immune cell infiltration in LUAD. Moreover, the mutation or different sCNA status of RCC2 exerted influence on multiple immune cell infiltration distribution. We found that the upregulation of RCC1 and RCC2 were obviously related to TP53 mutation. GSEA analysis revealed that RCC2 was involved in the process of DNA replication, nucleotide excision repair and cell cycle, which might affect tumor progression through P53 signaling pathway. We further elucidated that downregulation of RCC2 could dramatically repress the migration and invasion of LUAD cells. Conclusions: The study demonstrated that RCC1 and RCC2 expression were markedly increased in early-stage of LUAD. Patients with high expression of RCC1 or RCC2 had a worse prognosis. Based on our analysis, RCC1 and RCC2 might exert influence on LUAD process through DNA replication, nucleotide excision repair and cell cycle, as well as cells migration and invasion. Different from RCC1, RCC2 also involved in immune infiltration. These analyses provided a novel insight into the identification of diagnostic biomarker.
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Objective: This study aimed to elucidate the underlying mechanism of LncRNA PRKCA-AS1 in lung adenocarcinoma (LUAD). Methods: The expression of LncRNA PRKCA-AS1, miR-508-5p and S100A16, in LUAD tissues or cell lines (NCI-H520 and H1299) was analyzed with qRT-PCR. The clinical diagnostic value of LncRNA PRKCAAS1, miR-508-5p and S100A16 in LUAD were analyzed by receptor operating characteristic (ROC) curve. Then we knockdown or overexpression of PRKCAAS1 in NCI-H520 and H1299 cells, and the cell function test was applied to detect the activity and metastasis level of cells in different transfection groups. Then Pearson correlation analysis was used for the correlation between miR-508-5p and PRKCA-AS1. The dual-luciferase reporter experiment and CHIRP analysis was conducted to verify the target binding relationship of PRKCA-AS1, miR-508-5p or S100A16. FISH assay analyzed the colocalization of PRKCA-AS1 and miR-508-5p in NCI-H520 and H1299 cells. Rescue experiment and tumorigenesis experiment in nude mice further explore the regulatory mechanisms of LncRNA PRKCA-AS1, miR-508-5p and S100A16 on LUAD progression in vitro and in vivo. Results: From the results, PRKCA-AS1 and S100A16 were up-regulated in LUAD tissues, while miR-508-5p was downregulated compared with the adjacent tissues. And gain-of-function revealed that PRKCA-AS1 knock-down apparently suppressed the cell proliferation and metastasis, whereas miR-508-5p inhibitors or S100A16 overexpression showed a opposite effect. In addition, there is evidence that PRKCA-AS1, miR-508-5p and S100A16 have a targeted regulatory relationship. Moreover, rescue experiment and tumorigenesis experiment in nude mice further confirmed that LncRNA PRKCA-AS1 regulates S100A16 through sponging miR-508-5p to regulate LUAD progression in vitro and in vivo. Conclusion: These results demonstrated that LncRNA PRKCA-AS1 might regulate LUAD by acting as a ceRNA via sponging miR-508-5p and regulating S100A16 expression, indicating that manipulation of PRKCA-AS1 might be a potential therapeutic strategy in LUAD.
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BACKGROUND: In patients with acute cardiogenic cerebral embolism, a residual thrombus may still be present in the cardiac cavity even after reperfusion therapy. We aimed to investigate the occurrence of a residual cardiac thrombus in cardioembolic stroke after reperfusion therapy and analyze its impact on clinical outcome. METHODS AND RESULTS: We enrolled patients with cardioembolic stroke from our prospectively collected database who underwent 2-phase cardiac computed tomography within 7 days after reperfusion therapy. Residual cardiac thrombus was defined as a filling defect on both early- and late-phase images, whereas circulatory stasis was defined as a filling defect only on the early-phase images in the left atrial appendage. The primary outcome was a poor clinical outcome (modified Rankin Scale score, 3-6) at 90 days. The secondary outcome was a composite end point event (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke) at 90 days. A total of 303 patients were included, of whom 94 (31.0%) had a residual cardiac thrombus. Binary logistic regression analysis showed that the presence of a residual cardiac thrombus was associated with a poor clinical outcome (odds ratio, 1.951 [95% CI, 1.027-3.707]; P=0.041) but not circulatory stasis in the left atrial appendage (odds ratio, 1.096 [95% CI, 0.542-2.217]; P=0.798). Furthermore, there was no correlation between a residual cardiac thrombus and the composite end point event (30.0% versus 31.1%; P=1.000). CONCLUSIONS: Residual cardiac thrombus occurs in approximately one-third of patients with cardioembolic stroke after reperfusion therapy and is often indicative of a poor clinical outcome.
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Apéndice Atrial , Accidente Cerebrovascular Embólico , Accidente Cerebrovascular , Trombosis , Humanos , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/epidemiología , Apéndice Atrial/diagnóstico por imagen , Trombosis/diagnóstico por imagen , Trombosis/etiología , ReperfusiónRESUMEN
BACKGROUND: While intravenous thrombolysis is recommended for patients who had an acute ischaemic stroke (AIS) within 4.5 hours of symptom onset, there are few randomised trials investigating the benefits of thrombolysis beyond this therapeutic window. AIM: To determine whether patients who had an AIS selected with the presence of potentially salvageable tissue on CT perfusion at 4.5-24 hours after stroke onset (for stroke with unknown onset time, the midpoint of the time last known to be well and symptom recognition time; for wake-up stroke, the midpoint of the time last known to be well or sleep onset and wake up time) will benefit from intravenous thrombolysis. DESIGN: HOPE is a prospective, multicentre, randomised, open-label blinded endpoint trial with the stage of phase III. The treatment allocation employs 1:1 randomisation. The treatment arm under investigation is alteplase with standard therapy, the control arm is standard therapy. Eligibility imaging criteria include ischaemic core volume ≤70 mL, penumbra ≥10 mL and mismatch ≥20%. STUDY OUTCOMES: The primary outcome is non-disabled functional outcome (assessed as modified Rankin Scale score of 0-1 at 90 days). DISCUSSION: HOPE is the first trial to investigate whether intravenous thrombolysis with alteplase offers benefits in patients who had an AIS presenting within 4.5-24 hours, which has the potential to extend time window and expand eligible population for thrombolysis therapy.
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Recent efforts on learning-based image denoising approaches use unrolled architectures with a fixed number of repeatedly stacked blocks. However, due to difficulties in training networks corresponding to deeper layers, simply stacking blocks may cause performance degradation, and the number of unrolled blocks needs to be manually tuned to find an appropriate value. To circumvent these problems, this paper describes an alternative approach with implicit models. To our best knowledge, our approach is the first attempt to model iterative image denoising through an implicit scheme. The model employs implicit differentiation to calculate gradients in the backward pass, thus avoiding the training difficulties of explicit models and elaborate selection of the iteration number. Our model is parameter-efficient and has only one implicit layer, which is a fixed-point equation that casts the desired noise feature as its solution. By simulating infinite iterations of the model, the final denoising result is given by the equilibrium that is achieved through accelerated black-box solvers. The implicit layer not only captures the non-local self-similarity prior for image denoising, but also facilitates training stability and thereby boosts the denoising performance. Extensive experiments show that our model leads to better performances than state-of-the-art explicit denoisers with enhanced qualitative and quantitative results.
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BACKGROUND: Our aim was to expose the effect of miR-508-5p on the developmental and biological behaviour of lung adenocarcinoma (LUAC). METHODS: The KM plotter was used to analyze the survival significance of miR-508-5p and S100A16 expression in LUAC patients. qRT-PCR was performed to detect the expression of miR-508-5p and S100A16 in LUAC tissue and LUAC cell lines. CCK8, colony formation and Transwell were performed to evaluate the effects of miR-508-5p and S100A16 on cell proliferation and metastasis. Dual luciferase reporter assay was used to verify that S100A16 were targets of miR-508-5p. Western blot analysis was performed to analyze protein expression. RESULTS: Results showed that low miR-508-5p expression in LUAC tissues indicated poorer overall survival of LUAC patients and miR-508-5p was downregulated in LUAC cell lines compared to the normal human lung epithelial cell line. miR-508-5p mimics could inhibit A549 cell proliferation and metastasis abilities, while miR-508-5p Antagomir showed the opposite effect. We identified S100A16 as one direct target of miR-508-5p, and rescuing S100A16 expression could reverse the effect of miR-508-5p mimics on A549 cell proliferation and metastasis. miR-508-5p could involve the coordination of AKT signaling and epithelial-mesenchymal transition (EMT) progress using western-blot assays and rescuing S100A16 expression could reverse the inhibited AKT signaling and EMT progress induced by miR-508-5p mimics. CONCLUSIONS: We found that miR-508-5p targeted S100A16 to regulate AKT signaling and EMT progress in A549 cells, resulting in impaired cell proliferation and metastasis activity, suggesting that miR-508-5p might be a promising therapeutic target and an important diagnostic and prognostic marker for improved LUAC therapeutic schedule.
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Adenocarcinoma del Pulmón , Adenocarcinoma , Neoplasias Pulmonares , MicroARNs , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transición Epitelial-Mesenquimal/genética , Línea Celular Tumoral , Movimiento Celular , Adenocarcinoma del Pulmón/genética , Adenocarcinoma/genética , Adenocarcinoma/patología , Proliferación Celular/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Genes Supresores de Tumor , Regulación Neoplásica de la Expresión Génica , Proteínas S100/genética , Proteínas S100/metabolismoRESUMEN
Malignant melanoma is one of the most aggressive of cancers; if not treated early, it can metastasize rapidly. Therefore, drug therapy plays an important role in the treatment of melanoma. Cinobufagin, an active ingredient derived from Venenum bufonis, can inhibit the growth and development of melanoma. However, the mechanism underlying its therapeutic effects is unclear. The purpose of this study was to predict the potential targets of cinobufagin in melanoma. We gathered known and predicted targets for cinobufagin from four online databases. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were then performed. Gene expression data were downloaded from the GSE46517 dataset, and differential gene expression analysis and weighted gene correlation network analysis were performed to identify melanoma-related genes. Using input melanoma-related genes and drug targets in the STRING online database and applying molecular complex detection (MCODE) analysis, we identified key targets that may be the potential targets of cinobufagin in melanoma. Moreover, we assessed the distribution of the pharmacological targets of cinobufagin in melanoma key clusters using single-cell data from the GSE215120 dataset obtained from the Gene Expression Omnibus database. The crucial targets of cinobufagin in melanoma were identified from the intersection of key clusters with melanoma-related genes and drug targets. Receiver operating characteristic curve (ROC) analysis, survival analysis, molecular docking, and molecular dynamics simulation were performed to gain further insights. Our findings suggest that cinobufagin may affect melanoma by arresting the cell cycle by inhibiting three protein tyrosine/serine kinases (EGFR, ERBB2, and CDK2). However, our conclusions are not supported by relevant experimental data and require further study.
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OBJECTIVE: To develop a nonenhanced CT-based radiomic signature for the differentiation of iodinated contrast extravasation from intraparenchymal haemorrhage (IPH) following mechanical thrombectomy. METHODS: Patients diagnosed with acute ischaemic stroke who underwent mechanical thrombectomy in 4 institutions from December 2017 to June 2020 were included in this retrospective study. The study population was divided into a training cohort and a validation cohort. The nonenhanced CT images taken after mechanical thrombectomy were used to extract radiomic features. The maximum relevance minimum redundancy (mRMR) algorithm was used to eliminate confounding variables. Afterwards, least absolute shrinkage and selection operator (LASSO) logistic regression was used to generate the radiomic signature. The diagnostic performance of the radiomic signature was evaluated by the area under the curve (AUC), accuracy, specificity, sensitivity, positive predictive value (PPV), and negative predictive value (NPV). RESULTS: A total of 166 intraparenchymal areas of hyperattenuation from 101 patients were used. The areas of hyperattenuation were randomly allocated to the training and validation cohorts at a ratio of 7:3. The AUC of the radiomic signature was 0.848 (95% confidence interval (CI) 0.780-0.917) in the training cohort and 0.826 (95% CI 0.705-0.948) in the validation cohort. The accuracy of the radiomic signature was 77.6%, with a sensitivity of 76.7%, a specificity of 78.9%, a PPV of 85.2%, and a NPV of 68.2% in the validation cohort. CONCLUSIONS: The radiomic signature constructed based on initial post-operative nonenhanced CT after mechanical thrombectomy can effectively differentiate IPH from iodinated contrast extravasation. KEY POINTS: ⢠Radiomic features were extracted from intraparenchymal areas of hyperattenuation on initial post-operative CT scans after mechanical thrombectomy. ⢠The nonenhanced CT-based radiomic signature can differentiate IPH from iodinated contrast extravasation early. ⢠The radiomic signature may help prevent unnecessary rescanning after mechanical thrombectomy, especially in cases where contrast extravasation is highly suggestive.
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Isquemia Encefálica , Accidente Cerebrovascular , Medios de Contraste , Extravasación de Materiales Terapéuticos y Diagnósticos , Hemorragia , Humanos , Estudios Retrospectivos , Trombectomía , Tomografía Computarizada por Rayos X/métodosRESUMEN
BACKGROUND: Accumulating evidence indicates that long non-coding RNAs (lncRNAs) are involving in the tumorigenesis and metastasis of lung cancer. The aim of the study is to systematically characterize the lncRNA-associated competing endogenous RNA (ceRNA) network and identify key lncRNAs in the development of stage I lung adenocarcinoma (LUAD). METHODS: Totally, 1,955 DEmRNAs, 165 DEmiRNAs and 1,107 DElncRNAs were obtained in 10 paired normal and LUAD tissues. And a total of 8,912 paired lncRNA-miRNA-mRNA network was constructed. Using the Cancer Genome Atlas (TCGA) dataset, the module of ME turquoise was revealed to be most relevant to the progression of LUAD though Weighted Gene Co-expression Network Analysis (WGCNA). RESULTS: Of the lncRNAs identified, LINC00639, RP4-676L2.1 and FENDRR were in ceRNA network established by our RNA-sequencing dataset. Using univariate Cox regression analysis, FENDRR was a risk factor of progression free survival (PFS) of stage I LUAD patients (HRs = 1.69, 95%CI 1.07-2.68, P < .050). Subsequently, diffe rential expression of FENDRR in paired normal and LUAD tissues was detected significant by real-time quantitative (qRT-PCR) (P < 0.001). CONCLUSIONS: This study, for the first time, deciphered the regulatory role of FENDRR/miR-6815-5p axis in the progression of early-stage LUAD, which is needed to be established in vitro and in vivo.
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Adenocarcinoma del Pulmón/genética , Factores de Transcripción Forkhead/genética , Redes Reguladoras de Genes/genética , Neoplasias Pulmonares/genética , ARN Largo no Codificante/genética , Adenocarcinoma del Pulmón/mortalidad , Biomarcadores de Tumor/genética , Humanos , Neoplasias Pulmonares/mortalidad , MicroARNs/genética , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , ARN Mensajero/genéticaRESUMEN
BACKGROUND: To identify hub genes from the competing endogenous RNA (ceRNA) network of lung adenocarcinoma (LUAD) and to explore their potential functions on prognosis of patients from a single-cell perspective. METHODS: We performed RNA-sequencing of LUAD to construct ceRNA regulatory network, integrating with public databases to identify the vital pathways related to patients' prognosis and to reveal the expression level of hub genes under different conditions, the functional enrichment of co-expressed genes and their potential immune-related mechanisms. RESULTS: ZC3H12D-hsa-miR-4443-ENST00000630242 axis was found to be related with LUAD. Lower ZC3H12D expression was significantly associated with shorter overall survival (OS) of patients (HR = 2.007, P < 0.05), and its expression was higher in early-stage patients, including T1 (P < 0.05) and N0 (P < 0.05). Additionally, ZC3H12D expression was higher in immune cells displayed by single-cell RNA-sequencing data, especially in Treg cells of lung cancer and CD8 T cells, B cells and CD4 T cells of LUAD. The functional enrichment analysis showed that the co-expressed genes mainly played a role in lymphocyte activation and cytokine-cytokine receptor interaction. In addition, ZC3H12D was associated with multiple immune cells and immune molecules, including immune checkpoints CTLA4, CD96 and TIGIT. CONCLUSION: ZC3H12D-hsa-miR-4443-ENST00000630242 ceRNA network was identified in LUAD. ZC3H12D could affect prognosis of patients by regulating mRNA, miRNA, lncRNA, immune cells and immune molecules. Therefore, it may serve as a vital predictive marker and could be regarded as a potential therapeutic target for LUAD in the future.
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Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/mortalidad , Proteínas de Ciclo Celular/genética , Endorribonucleasas/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Biomarcadores de Tumor/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes , Humanos , Estimación de Kaplan-Meier , Masculino , MicroARNs/genética , Pronóstico , ARN Largo no Codificante/genética , ARN Mensajero/genéticaRESUMEN
Background: Current clinical guidelines recommend systemic anticoagulation as the initial treatment for severe cerebral venous sinus thrombosis (CVST). However, anticoagulation alone does not always dissolve large and extensive CVSTs in some patients. Here, we investigated the effectiveness and safety of balloon-assisted thrombectomy and intrasinus urokinase thrombolysis in our retrospective study of a series of 23 patients with CVST. Methods: We reviewed the clinical, radiological, and outcome data of all patients. Complete recanalization was defined as all the occluded sinuses were recanalized on digital subtraction angiography or Contrast-enhanced magnetic resonance venography. Partial recanalization was defined as the complete recanalization of one sinus but persistent occlusion of other sinuses, or partial recanalization of one or more sinuses. The modified Rankin Scale (mRS) was used to represent the clinical outcome. Results: From May 2017 to November 2019, a total of 23 patients were treated with balloon-assisted thrombectomy and intrasinus urokinase thrombolysis. A total of 84 venous sinuses were involved, ≥3 sinuses were involved in 20 (87%) patients. Among them, 21 (91%) patients achieved technical success. Complete and partial recanalization were obtained in 17 (81%) and 4 (19%) patients at 6 months follow-up, respectively. All 21 patients had mRS scores of 0 (18) or 1 (3). Conclusions: Our case series shows that balloon-assisted thrombectomy combined with intrasinus urokinase thrombolysis and activated partial thromboplastin time-regulated systemic anticoagulation is safe and effective in treating severe CVST.
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BACKGROUND: Non-small cell lung cancer (NSCLC) is one of the most common malignancies with the highest morbidity and mortality worldwide. Long non-coding RNAs (lncRNAs) are recently recognized as noteworthy regulators of different tumors, counting NSCLC. However, the biological functions and regulatory mechanism of lncRNA WT1-AS in NSCLC progression still stay uninvestigated. METHODS: WT1-AS and miR-494-3p levels in NSCLC cell lines were detected by real-time quantitative polymerase chain reaction (RT-qPCR). In the current study, the regulatory effects of WT1-AS/miR-494-3p axis on cellular behaviors of NSCLC cell lines (A549 and NCI-H1975) were evaluated by a variety of methods. Cell counting kit-8 (CCK-8) and EDU assays were adopted to assess NSCLC cell proliferation. Tunnel staining and flow cytometry assay were applied to determine cell apoptosis and cell cycle distribution. Besides, cell migration and invasion abilities were analyzed by performing wound healing and transwell assays. Meanwhile, the levels of key proteins related to NSCLC cell apoptosis and PTEN/PI3K/AKT pathway were examined using Western blot assay. In addition, luciferase reporter assays were used to determine the interaction between WT1-AS and miR-494-3p or miR-494-3p and PTEN. RESULTS: Visibly downregulated WT1-AS in NSCLC cell lines was obtained from Broad Institute Cancer Cell Line Encyclopedia (CCLE) database and further verified by performing RT-qPCR. Besides, miR-494-3p was the downstream target gene of WT1-AS and obviously upregulated miR-494-3p in NSCLC cell lines was confirmed. WT1-AS overexpression suppressed cell proliferation, migration and invasion abilities while enhanced cell apoptosis of A549 and NCI-H1975 cells. Furthermore, upregulation of miR-494-3p distinctly reversed these inhibitory effects of WT1-AS overexpression on the tumorigenesis and progression of NSCLC. In addition, WT1-AS promoted PTEN expression and thereby inhibited activation of PI3K/AKT pathway by sponging miR-494-3p. CONCLUSION: To conclude, lncRNA WT1-AS impeded cell proliferation, migration, invasion but accelerated cell apoptosis via negatively regulating miR-494-3p to mediate PTEN/PI3K/AKT pathway in NSCLC.
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BACKGROUND: Esophageal cancer (EC) is globally acknowledged as one of the most common malignancies among all gastrointestinal cancers. Furthermore, in Eastern Asia, squamous cell carcinoma is the main pathological type of EC. There are different treatments for esophageal squamous cell carcinoma (ESCC), but there is still a lack of large-sample analysis of prognosis among different treatments, especially for different tumor stages. The analysis of the prognosis of ESCC patients with different treatments may be helpful to choose the treatment methods for different stages ESCC. METHODS: A total of 3,346 patients with pathological ESCC between 1976 and 2016 were derived from the Surveillance, Epidemiology, and End Results (SEER) database. All clinical factors associated with prognosis were collected and analyzed to achieve the difference of prognosis among different treatments in ESCC patients, such as ages, sex, race, tumor grade, anatomic location and so on. Kaplan-Meier and Cox proportional hazard analysis were used to compare survival of different treatments in ESCC patients with stage I-III. RESULTS: The overall survival (OS) in all ESCC patients who had received surgery and surgery plus radiation therapy or/and chemotherapy are superior than that had not received any treatments and radiation therapy or/and chemotherapy. The OS in ESCC patients with stage I who had received surgery and surgery plus radiation therapy or/and chemotherapy are superior than that had not received any treatments and radiation therapy or/and chemotherapy. The OS in ESCC patients with stage II/III who had received surgery and surgery plus radiation therapy or/and chemotherapy are superior than that in other groups. Age, race and grade as an independent predictive factor for survival (P<0.05). A nomogram model was constructed to show surgery group had better 1-, 3- and 5-year OS than radiation therapy or/and chemotherapy group (OS: 78.5% vs. 59.2%, 37.9% vs. 18.4%, 16.9% vs. 6.1%). CONCLUSIONS: Surgery is still the first choice for all ESCC patients with stage I-III. Radiotherapy and chemotherapy could improve the survival rate in ESCC patients with stage II-III who have received surgery.
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Biomarcadores de Tumor/sangre , Ferritinas/sangre , Neoplasias Pulmonares/diagnóstico , Factores de Edad , Anciano , Anciano de 80 o más Años , Antígenos de Neoplasias/sangre , Antígeno Ca-125/sangre , Diagnóstico Precoz , Femenino , Humanos , Queratina-19/sangre , Neoplasias Pulmonares/cirugía , Masculino , Fosfopiruvato Hidratasa/sangre , Valor Predictivo de las Pruebas , Pronóstico , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: The acquisition of invasive tumor cell behavior is considered to be the cornerstone of the metastasis cascade. Thus, genetic markers associated with invasiveness can be stratified according to patient prognosis. In this study, we aimed to identify an invasive genetic trait and study its biological relevance in lung adenocarcinoma. METHODS: 250 TCGA patients with lung adenocarcinoma were used as the training set, and the remaining 250 TCGA patients, 500 ALL TCGA patients, 226 patients with GSE31210, 83 patients with GSE30219, and 127 patients with GSE50081 were used as the verification data sets. Subtype classification of all TCGA lung adenocarcinoma samples was based on invasion-associated genes using the R package ConsensusClusterPlus. Kaplan-Meier curves, LASSO (least absolute contraction and selection operator) method, and univariate and multivariate Cox analysis were used to develop a molecular model for predicting survival. RESULTS: As a consequence, two molecular subtypes for LUAD were first identified from all TCGA all data sets which were significant on survival time. C1 subtype with poor prognosis has higher clinical characteristics of malignancy, higher mutation frequency of KRAS and TP53, and a lower expression of immune regulatory molecules. 2463 differentially expressed invasion genes between C1 and C2 subtypes were obtained, including 580 upregulation genes and 1883 downregulation genes. Functional enrichment analysis found that upregulated genes were associated with the development of tumor pathways, while downregulated genes were more associated with immunity. Furthermore, 5-invasion gene signature was constructed based on 2463 genes, which was validated in four data sets. This signature divided patients into high-risk and low-risk groups, and the LUDA survival rate of the high-risk group is significantly lower than that of the low-risk group. Multivariate Cox analysis revealed that this gene signature was an independent prognostic factor for LUDA. Compared with other existing models, our model has a higher AUC. CONCLUSION: In this study, two subtypes were identified. In addition, we developed a 5-gene signature prognostic risk model, which has a good AUC in the training set and independent validation set and is a model with independent clinical characteristics. Therefore, we recommend using this classifier as a molecular diagnostic test to assess the prognostic risk of patients with LUDA.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Invasividad Neoplásica/genética , Transcriptoma/genética , Adenocarcinoma del Pulmón/clasificación , Adenocarcinoma del Pulmón/diagnóstico , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/mortalidad , Anciano , Biomarcadores de Tumor/genética , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Neoplasias Pulmonares/clasificación , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
Increasing evidence has indicated that long noncoding RNAs (lncRNAs) could participate in diverse cancers. Among these, lymphoid enhancer-binding factor 1 antisense RNA 1 (LEF1-AS1) was recently identified as an oncogenic lncRNA, but little is known about its function in non-small-cell lung cancer (NSCLC). In the present study, we found that LEF1-AS1 was markedly upregulated in lung cancer tissues and could promote NSCLC cell proliferation and migration in vivo and in vitro. LEF1-AS1 could bind with miR-489 and further negatively regulate miR-489 to promote SRY-related HMG box transcription factor 4 (SOX4) expression. In conclusion, these data suggested that LEF1-AS1 promoted NSCLC tumorigenesis dependent on the miR-489-SOX4 axis and implicated the potential application of LEF1-AS1 for the prognosis and treatment of NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/genética , Factor de Unión 1 al Potenciador Linfoide/genética , ARN sin Sentido/genética , ARN Largo no Codificante/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Femenino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Factor de Unión 1 al Potenciador Linfoide/metabolismo , Masculino , MicroARNs/genética , MicroARNs/metabolismo , Persona de Mediana Edad , Factores de Transcripción SOXC/genética , Factores de Transcripción SOXC/metabolismo , Regulación hacia ArribaRESUMEN
OBJECTIVE: 18F-FDG PET-CT is a noninvasive approach extensively used to assess the therapeutic results and give a prognosis for esophageal cancer. This study is focused on examining the predictive value of metabolic tumor volume (MTV) and pre-treatment maximal standardized uptake value (SUVmax) of short-term curative effects demonstrated in patients with esophageal cancer. METHODS: This study carried out a retrospective analysis of 98 patients diagnosed with esophageal cancer who received treatment by radiotherapy or a combination of chemotherapy and radiotherapy in the Second Affiliated Hospital of Fujian Medical University. 18F-FDG PET-CT scan was carried out prior to the treatment. PET/CT images before treatment were evaluated by two high-level professional doctors as a double-blind method. MTV and SUVmax values were averaged and confirmed. In 1 to 3 months after the treatment, a deputy director of PET/CT center with much experience and a radiotherapist assessed the curative effect of all patients in line with the Response Evaluation Criteria in Solid Tumor (RECIST). RESULTS: No considerable difference in SUVmax and MTV was observed between the two groups in cancer site, gender, age, or differential extent. In addition, there was a significant correlation between SUVmax and lesion length, lymph node metastasis, depth of invasion, and clinical stage. SUVmax was positively correlated to depth of invasion, lymph node metastasis, MTV, lesion length, and clinical stage. The value of effective rate was up to 67.3% (66/98). There was a negative correlation between MTV as well as SUVmax, and curative effects in the short term, whereas the curative effects of MTV exceeded that of SUVmax. CONCLUSION: MTV and SUVmax before treatment serve to forecast curative effects in the short term of radiotherapy or combination of chemotherapy and radiotherapy for patients with esophageal cancer. MTV had a greater predictive effect than SUVmax.