BackgroundAbnormal microRNA expression is closely related to cancer occurrence and development. miR-365a-3p plays an oncogenic role in skin cancer, but its role in lung cancer remains unclear. In this study, we aimed to investigate its role and underlying molecular mechanisms in lung cancer.MethodsWestern blot and real-time quantitative PCR (qPCR) were used to detect the expression of miR-365a-3p in lung adenocarcinoma and lung cancer cell lines. The effects of miR-365a-3p on lung cancer cell proliferation, migration, and invasion were also explored in vitro. The potential miR-365a-3p that targets USP33 was determined by dual luciferase reporter assay and verified by qPCR and western blot analysis. miR-365a-3p acts as an oncogene by promoting lung carcinogenesis via the downregulation of the miR-365a/USP33/SLIT2/ROBO1 axis based on western blot analysis. Subcutaneous tumourigenesis further demonstrated that miR-365a-3p promotes tumour formation in vivo.ResultsmiR-365a-3p was upregulated in lung adenocarcinoma and lung cancer cell lines. Overexpression of miR-365a-3p promoted and inhibition of miR-365a-3p suppressed the proliferation, migration, and invasion of lung cancer cells. We identified USP33 as the downstream target of miR-365a-3p and observed a negative correlation between miR-365a-3p and USP33 expression in lung adenocarcinoma patients. The miR-365/USP33/SLIT2/ROBO1 axis, a new mechanism, was reported to inhibit the invasion and metastasis of lung cancer. A nude mouse model of lung cancer further verified these findings.ConclusionsIn summary, miR-365a-3p acts as an oncogene by promoting lung carcinogenesis via the downregulation of the USP33/SLIT2/ROBO1 signalling pathway, making the miR-365/USP33/SLIT2/ROBO1 axis a new mechanism of lung cancer promotion and a novel therapeutic target for predicting prognosis and response to gene therapy.Electronic supplementary materialThe online version of this article (10.1186/s12935-018-0563-6) contains supplementary material, which is available to authorized users.
Objectives. As coronavirus disease 2019 (COVID-19) continues to spread globally, we aimed to describe and compare changes in the immune and cardiovascular systems of patients with mild versus severe COVID-19 at different time points during the course of disease. Methods. One hundred and one patients diagnosed with COVID-19 who underwent serial peripheral blood collection and chest computed tomography (CT) imaging were enrolled in this study and grouped by the severity of their illness. Changes in the immune and cardiovascular systems were analysed and compared between groups. Results. The study included 43 women and 58 men, with a median age of 45 years (interquartile range [IQR], 16-71). We identified spleen shrinkage in 27.7% of study patients. Ratios of spleen volume to patient (skin) volume were compared, with evidence that severe patients had more splenic shrinkage than mild patients. Lymphopenia was observed in 65.3% of patients, and 27.3% of patients had persistently low levels of lymphocytes after discharge. Tachycardia occurred mainly during the first 2 days of hospitalisation, with increases in creatine kinase-myocardial band levels in 10 (9.9%) patients and arrhythmias in 16 (15.8%) patients. Conclusions. In addition to pulmonary manifestations, our study demonstrated that other organ systems can also be affected during COVID-19 infection, with evidence of immunosuppression and cardiovascular dysfunction, which may contribute to increased mortality rates in critically ill COVID-19 patients.
Purpose Primary pulmonary lympho-epithelioma-like carcinoma (PPLELC) is a rare subtype of primary non-small cell lung cancer (NSCLC). Currently, there is still lack of research data on anti-angiogenic therapy of advanced PPLELC. The purpose of this study was to investigate the efficacy and safety of anti-angiogenic therapy combined with chemotherapy compared with traditional chemotherapy for these patients. Methods Advanced PPLELC patients admitted to six grade A hospitals from January 2013 to January 2021 were selected. The patients received anti-angiogenic therapy combined with chemotherapy (AT group) or chemotherapy (CT group) alone. Results A total of 65 patients were included in this study, including 31 patients in the AT group treated with anti-angiogenic therapy combined with chemotherapy and 34 patients in the CT group treated with chemotherapy alone. As of October 1, 2021, the median progression-free survival (PFS) in the AT group was 11.2 months [95% confidence interval (CI), 5.9–16.5]. The median PFS in the CT group was 7.0 months [95%CI, 5.1–8.9] [Hazard Ratio (HR), 0.49; 95%CI, 0.29–0.83; P = 0.008]. The 1-year PFS rates were 41.9% and 17.6%, respectively. The overall response rates (ORR) of two groups were 45.2% (95% CI, 0.27–0.64), 38.2% (95% CI, 0.21–0.56), (P = 0.571). The disease control rates (DCR) of two groups were 93.5% (95% CI, 0.84–1.03), 88.2% (95% CI, 0.77–1.00), (P = 0.756). Conclusion Among patients with advanced PPLELC, the PFS of patients with anti-angiogenic therapy combined with chemotherapy is better than that of patients with chemotherapy alone. Anti-angiogenic therapy combined with chemotherapy is an optional treatment scheme.
Objectives Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) is a rare subtype of primary non-small cell lung cancer (NSCLC), and the first-line therapy for metastatic PPLELC patients remains controversial. The purpose of this study was to investigate the efficacy and safety of immune checkpoint inhibitors(ICIs) combined with chemotherapy(CT) compared with traditional chemotherapy in these patients. Methods A total of 168 patients with metastatic PPLELC came from six grade A hospitals from August 2018 to August 2020 were selected. 17 patients were enrolled in the ICI group and received 200mg of Pembrolizumab plus albumin paclitaxel and carboplatin every 3 weeks. 34 patients with chemotherapy alone were assigned to the CT group and received albumin-paclitaxel combined with carboplatin every 3 weeks. Results As of June 1, 2021, the median PFS was 14.9 months for ICI group and 6.4 months for CT group [Hazard Ratio (HR), 0.29; 95% confidence interval (CI), 0.15-0.55; P < 0.05]. ORR was 64.7% in ICI group and 35.3% in CT group [HR, 0.65; 95%CI, 0.39-0.90; P=0.047]. The median OS of ICI group was not reached, while that of CT group was 13 months. In the ICI group, there were 8 cases (47.1%) of grade 3 treatment-related adverse reactions and 5 cases (29.4%) of grade 4 treatment-related adverse reactions. In the CT group, there were 9 cases (26.5%) of grade 3 treatment-related adverse reactions and 8 cases (23.5%) grade 4 treatment-related adverse reactions. FBXW7 mutation were negatively and TP53 mutation, MRE11A p.V198S mutation, PTEN p.T319FS mutation were positively correlated with the efficacy of immunotherapy. Conclusions In patients with metastatic PPLELC, the efficacy of immune checkpoint inhibitors combined with chemotherapy was significantly better than that of chemotherapy alone, and adverse reactions were acceptable.
Purpose: Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) is a rare subtype of primary non-small cell lung cancer (NSCLC). Currently, there is still lack of research data on anti-angiogenic therapy of advanced PPLELC. The purpose of this study was to investigate the efficacy and safety of anti-angiogenic therapy combined with chemotherapy compared with traditional chemotherapy for these patients.Methods: Advanced PPLELC patients admitted to six grade A hospitals from January 2013 to January 2021 were selected. The patients received anti-angiogenic therapy combined with chemotherapy(AT group) or chemotherapy (CT group)alone.Results: A total of 65 patients were enrolled in this study, including 31 patients in the AT group treated with anti-angiogenic therapy combined with chemotherapy, and 34 patients in the CT group treated with chemotherapy alone. As of October 1, 2021, the median progression-free survival in the AT group was 11.2 months [95% confidence interval (CI), 5.9-16.5], The median progression-free survival in the CT group was 7.0 months [95%CI, 5.1-8.9][Hazard Ratio (HR), 0.49; 95%CI, 0.29-0.83; P=0.008]. The 1-year PFS rates were 41.9% and 17.6%, respectively. The ORR of two groups were 45.2% (95% CI, 0.27 to 0.64), 38.2% (95% CI, 0.21 to 0.56), (P = 0.571). The DCR of two groups were 93.5% (95% CI, 0.84 to 1.03), 88.2% (95% CI, 0.77 to 1.00), (P = 0.756).Conclusions: Among patients with advanced PPLELC, the progression free survival of patients with anti-angiogenic therapy combined with chemotherapy is better than that of patients with chemotherapy alone. Anti-angiogenic therapy combined with chemotherapy is an optional treatment scheme.
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