BackgroundAlthough many studies have defined mechanisms of resistance to EGFR‐TKIs, acquired resistance remains the major limitation of monotherapy with EGFR‐TKIs.MethodsCell viability was analyzed using a Cell Counting Kit‐8 (CCK‐8) assay. EGFR T790M mutation was sequenced on a HiSeq 4000 platform. mRNAs from HCC827 and HCC827 gefitinib‐resistant (GR) cells were analyzed by genome analyzer‐based deep sequencing. The effect of anlotinib on apoptosis and cell cycle arrest of HCC827 GR was detected by fluorescence‐activated cell sorting (FACS) analysis. A mouse xenograft model was used to assess the effect of anlotinib on HCC827 GR cells.ResultsThe T790M mutation was found in the PC‐9 GR cell line but not in the HCC827 GR cell line. Anlotinib could suppress the growth of HCC827 GR cells by inhibiting FGFR1 in vitro and in a mouse xenograft model. Moreover, FGFR1 was overexpressed in HCC827 GR cells, and the knockdown of FGFR1 reversed gefitinib resistance in HCC827 GR cells. Furthermore, anlotinib induced apoptosis and cell cycle arrest in HCC827 GR cells by increasing the activity of Caspase‐3.ConclusionsFGFR1 overexpression could be the mechanism of EGFR‐TKI acquired resistance and anlotinib can suppresse the growth of EGFR‐TKI‐resistant NSCLC cells without T790M mutation.

Background Although many studies have defined mechanisms of resistance to EGFR-TKIs, acquired resistance remains the major limitation of monotherapy with EGFR-TKIs. Therefore, there is an urgent need to develop effective therapeutic interventions to overcome acquired resistance. Methods Cell viability was analysed using CCK‐8 assay. EGFR T790M mutation was sequenced on a HiSeq 4000 platform. mRNA from HCC827 and HCC827 gefitinib-resistant (GR) cells was analysed by genome analyser-based deep sequencing. The effect of anlotinib on apoptosis and cell cycle arrest of HCC827 GR was detected by fluorescence-activated cell sorting (FACS) analysis. A mouse xenograft model was used to assess the killing effect of anlotinib on HCC827 GR cells. Results Here we found the T790M mutation in the PC-9 gefitinib-resistant (GR) cell line but not in the HCC827 GR cell line. Interestingly, anlotinib could suppress the growth of HCC827 GR cells by inhibiting FGFR1 in vitro and in a mouse xenograft model. Moreover, FGFR1 was overexpressed in HCC827 GR cells, and the knockdown of FGFR1 reversed gefitinib resistance in HCC827 GR cells. Furthermore, anlotinib induced apoptosis and cell cycle arrest in HCC827 GR cells by increasing the activity of Caspase-3 and decreasing the expression of Cyclin D1. Conclusion FGFR1 overexpression is one of the mechanisms of EGFR-TKI acquired resistance and anlotinib can suppresses the growth of EGFR-TKI-resistant NSCLC cells without T790M mutation.

Mitochondrial fission regulator 2 (MTFR2) belongs to the MTFR1 family, which plays a crucial role in regulating oxidative phosphorylation. Recent studies indicate that it also participates in cancer carcinogenesis and development; however, the clinical significance of MTFR2 in lung adenocarcinoma has not been fully confirmed. Our current study investigated the relationships between clinical characteristics and MTFR2 expression based on The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GSE31210) dataset, and clinical histopathological sample cohort. In addition, Kaplan–Meier and Cox regression analyses were additionally performed to evaluate the association between MTFR2 expression and patient survival. Gene set enrichment analysis (GESA) was conducted to spot possible pathways associated with MTFR2. Moreover, a single-sample GESA (ssGESA) was performed to evaluate the association between MTFR2 expression and immune cell infiltration. Cell colony formation assay, CCK-8 assay, cell cycle assay, and transwell assay were performed to verify the cell proliferation, migration, and invasion abilities after interfering with MTFR2 in lung cancer cells. Western blot assay was applied to identify the underlying protein levels. The results indicated that the elevated MTFR2 expression in lung adenocarcinoma samples correlated with T stage (P < 0.001), N stage (P = 0.005), M stage (P = 0.015), pathological stage (P = 0.002), and TP53 status (P < 0.001). Patients with a higher MTFR2 expression correlated with poorer overall survival (P < 0.01) and progression-free survival (P = 0.002). Knockdown of MTFR2 inhibited cell proliferation, migration, and invasion via AKT-cyclin D1 signaling and EMT pathways. Moreover, MTFR2 expression significantly positively correlated with Th2 cells (P < 0.001). Taken together, MTFR2 could serve as a novel prognostic indicator and therapeutic target for lung adenocarcinoma.

Background: In less than a year, COVID-19 has swept the world and continued, too, seriously threatening the safety of all mankind, and caused great social panic and global economic and financial crisis. At the beginning, the epidemic was first diagnosed in China and the epidemic was severe. Under the strong command of the highest level of the Chinese government, the whole Chinese people united as one, and achieved initial results in the struggle against COVID-19 with scientific prevention and control. Objective: Summarizing China's experience and lessons in combating the epidemic is undoubtedly very beneficial to the people of the world in jointly combating the impact of the COVID-19 epidemic. Measures: The article shows the imminent Chinese experience in controlling the spread of SARS-CoV-2. It details the lines of action and the measures taken to control this epidemic in the country where the population is quite large. The most important experience is: strong organizational leadership, enhanced cooperation with the WHO, the establishment of a national anti-epidemic headquarters, responsible for the command and control of human, financial and material resources throughout the country, and local officials at all levels in the front line of the epidemic, Heart to heart with the people, breathing together and sharing a common destiny. Prevention is the first, prevention and treatment are combined. All measures were taken to control the source of infection, cut off the spread and protect susceptible people. Conclusion: As long as the people of the world unite, make scientific decisions and learn from the successful experience of countries around the world, especially the China's experience, combine the national conditions of each country, and use the wisdom of all man-kind to deal with the common enemy SARS-CoV-2 and COVID-19, we can definitely win this people's war against the disease.