Crizotinib is an orally administered drug for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive locally advanced or metastatic non-small cell lung cancer (NSCLC). Despite the impressive efficacy of crizotinib in the treatment of ALK-positive lung cancer, acquired resistance eventually develops in the majority of patients. The microRNA (miR)-200c reverses the resistance of lung cancer cells to various chemotherapeutic drugs and molecular targeted drugs, however, whether it can reverse the resistance of crizotinib remains unknown. The present study established a crizotinib resistant cell line (NCI-2228/CRI), which was derived from the parental NCI-2228 cell line by long-term exposure to increasing concentrations of crizotinib. Through overexpression and suppression of miR-200c expression, the characteristics associated with epithelial-mesenchymal transition (EMT), including morphology, EMT marker proteins and cellular mobility, were investigated. Cell viability and invasion assays demonstrated that high expression of miR-200c significantly inhibited the proliferation, migration and invasion of NCI-2228 cells compared with the negative control. A luciferase reporter assay indicated that miR-200c directly targeted the 3′-untranslated region of zinc finger E-box binding homeobox 1. Additionally, reverse transcription-quantitative polymerase chain reaction analysis demonstrated that the mRNA levels of N-cadherin and Vimentin were decreased in NCI-2228 cells transfected with miR-200c mimic compared with negative control cells, whereas the mRNA level of E-cadherin was increased. In addition, EMT was reversed by miR-200c, which suggests that miR-200c may serve a role in mediating the sensitivity of NCI-2228/CRI cells to crizotinib. The present study may therefore contribute to improving the sensitivity of ALK positive lung cancer cells to crizotinib.
Background Due to the latent onset of novel coronavirus disease 2019 (COVID-19), it is important to identify patients with increased probabilities for disease progression early in order to implement timely medical strategies. This study aimed to identify the factors associated with increased COVID-19 severity and evaluate the current antiviral drugs, especially in severe patients. Methods This was a retrospective observational study performed at the No. 7 Hospital of Wuhan (Wuhan, China) with hospitalized patients confirmed with COVID-19 from January 11 to March 13, 2020. Multivariable logistic regression analysis was used to identify the associated factors of severe COVID. Treatments of antivirus drugs were collected and evaluated. Results Of the 550 patients, 292 (53.1%) were female and 277 (50.4%) were > 60 years old. The most common symptom was fever (n = 372, 67.7%), followed by dry cough (n = 257, 46.7%), and dyspnea (n = 237, 43.1%), and fatigue (n = 224, 40.7%). Among the severe patients, 20.2% required invasive ventilator support and 18.0% required non-invasive ventilator. The identified risk factors for severe cases were: age ≥ 60 years (odds ratio (OR) =3.02, 95% confidence interval (CI): 1.13–8.08, P = 0.028), D-dimer > 0.243 μg/ml (OR = 2.734, 95%CI: 1.012–7.387, P = 0.047), and low oxygenation index (OR = 0.984, 95%CI: 0.980–0.989, P < 0.001). In severe cases, the benefits (relief of clinical symptoms, clinical outcome, and discharge rate) of arbidol alone was 73.3%, which was better than ribavirin (7/17, 41.2%, P = 0.029). Conclusions Age > 60 years, D-dimer > 0.243 μg/ml, and lower oxygenation index were associated with severe COVID-19. Arbidol might provide more clinical benefits in treating patients with severe COVID-19 compared with ribavirin.
We investigated the possible implication of miR-23a in anoxia-induced phenotypic transformation of the pulmonary arterial smooth muscle and studied the mechanism of upregulation of miR-23a expression in anoxia. The collagenase digestion method was used for preparing rat primary pulmonary artery smooth muscle cell (PASMC) culture. SM-MHC, SM-α-actin, calponin-1 and SM22α protein expression levels were evaluated using western blot analysis after the ASMCs were subjected to anoxia treatment (3% O2). Transfection with miR-23a mimics were conducted when PASMCs were under normoxia and anoxia conditions. EdU staining was used to detect the proliferative activity of PASMCs. Cells were transfected with HIF-1α specific siRNA under anoxia condition. RT-qPCR was used to detect miR-23a expression in PASMCs. Chromatin immunoprecipitation method was employed to verify the binding sites of HIF-1α. The dual-luciferase reporter gene was used to study the role of HIF-1 and its binding sites. Rat hypoxic pulmonary hypertension models were established to study the expression of miR-23a using RT-qPCR method and to verify the expression of miR-23a in the arteriole of the rat pulmonary. Our results showed that compared with normoxia condition, under anoxia condition (3% O2), the expression levels of the contractile phenotype marker proteins decreased significantly after 24 and 48 h. The positive rate of the EdU staining increased significantly and the expression of miR-23a increased. Transfection with miR-23a-mimic downregulated the expression of contractile marker proteins and improved the positive rate of the EdU staining under normoxia. Anoxia and transfection with HIF-1α enhanced the activity of the wild-type Luc-miR-23a-1 (WT) reporter gene. We concluded that miR-23a participated in the anoxia-induced phenotypic transformation of PASMCs. Increased expression of miR-23a under anoxia may primarily be due to miR-23a-1 and miR-23a-3 upregulation. The anoxia-induced upregulation of miR-23a was regulated by HIF-1.
Lung cancer is a disease characterized by the uncontrolled growth of cells in lung tissue. If left untreated, cell growth can spread beyond the lungs to a process called metastasis and reach surrounding tissues or other organs. This experiment was set up to discuss and analyze the research value of joint detection of tumor markers including carcino-embryonic antigen (CEA), cytokeratin 19 fragments (CYFRA21-1) and neuron-specific enolase (NSE) in the diagnosis and pathological type of lung cancer. From November 2016 to February 2018, 378 cases of patients with lung cancer treated in our hospital and 200 cases of people with healthy physical examinations were collected. The electrochemical immunoluminescence method was adopted to detect the CEA, CYFRA21-1 and NSE. The detected positive rate and the concentration of CEA, CYFRA21-1 and NSE of lung cancer group were higher than that of the healthy physical examination group.The differences were of statistical significance (P<0.05); the detected positive rate of CEA and CYFRA21-1 and the concentration of CEA, CYFRA21-1 and NSE of squamous carcinoma group were higher than that of the adenocarcinoma group. The differences were of statistical significance (P<0.05). The CEA, CYFRA21-1 and NSE are related to the pathological type of lung cancer and can be regarded as related indicators to diagnose lung cancer.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.