Gangliosides and CD82 inhibit the motility of colon cancer by downregulating the phosphorylation of EGFR at different tyrosine sites and signaling pathways
MOLECULAR MEDICINE REPORTS
Authors: Huang, Xiaohua; Li, Ying; He, Xin; Chen, Yang; Wei, Wei; Yang, Xuesong; Ma, Keli
Abstract
Previous studies have shown that (GM3), a ganglioside, suppresses hepatoma cell motility and migration by inhibiting phosphorylation of EGFR and the activity of the PI3K/AKT signaling pathway. Therefore, the aim of the present study was to investigate whether the combined treatment of CD82 with gangliosides can exert a synergistic inhibitory effect on cell motility and migration. Epidermal growth factor receptor (EGFR) signaling was studied for its role in the mechanism through which CD82 and gangliosides synergistically inhibit the motility and migration of SW620 human colon adenocarcinoma cells. GM3 and/or GM2 treatment, and/or overexpression of CD82 was performed in SW620 cells. High-performance thin layer chromatography, reverse transcription-quantitative PCR, western blotting and flow cytometry assays were used to confirm the content changes of GM2, GM3 and CD82. In addition, the phosphorylation of EGFR, MAPK and Akt were evaluated by western blot analysis. SW620 cell motility was investigated using wound healing analysis and chemotaxis migration assay. The combination of GM3 and GM2 with CD82 was found to markedly suppress EGF-stimulated SW620 cell motility compared with the individual factors or combination of GM2 or GM3 with CD82 by inhibiting the phosphorylation of EGFR. The results suggested that CD82 in combination with either GM2 or GM3 can exert a synergistic inhibitory effect on cell motility and migration; however, the synergistic mechanisms elicited by GM2 or GM3 with CD82 differ.
Treatment Patterns and Survival Outcomes of Non-Small Cell Lung Cancer Patients Initially Diagnosed With Brain Metastases in Real-World Clinical Practice
FRONTIERS IN ONCOLOGY
Authors: Chen, Xin-Ru; Hou, Xue; Dinglin, Xiao-Xiao; Liu, Yong-Dong; Li, Yin; Zheng, Wei; Li, De-Lan; Chen, Jing; Wu, Xiao-Liang; Wang, Kai-Cheng; Ma, Shu-Xiang; Zeng, Yin-Duo; Chen, Li-Kun
Abstract
Background This study aimed to comprehensively analyze the characteristics, treatment patterns, and survival outcomes of non-small-cell lung cancer (NSCLC) patients initially diagnosed with brain metastases (BMs) in real-world practice. Methods We enrolled NSCLC patients initially diagnosed with BMs between Jan 2004 and Jan 2018 in our institution. Patient demographics, treatment modalities, and survival outcomes were then analyzed. Brain localized treatment (BLT) included early brain radiotherapy (EBR), deferred brain radiotherapy (DBR), and surgery. Results A total of 954 patients were identified. Concerning initial treatment, 525 patients (55.0%) received systemic medication (SM)+BLT, 400 patients (41.9%) received SM only, and 29 patients received BLT only (3.0%). SM+BLT cohort was associated with longer median overall survival (mOS) than the SM only and the BLT only cohorts both in epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK)-negative/unknown patients (15.3 months, 95% confidence interval [CI], 14.2-16.4; 11.1 months, 9.0-13.2; 7.0 months, 5.4-8.6; p<0.001) and in EGFR/ALK-positive patients (33.7 months, 28.5-38.9; 22.1 months, 17.8-26.4; 4.0 months, 3.6-4.4; p < 0.001). As for timing of radiotherapy, SM+EBR (14.1 months, 12.7-15.5) was associated with inferior mOS than SM+DBR (19.4 months, 14.2-24.6) in EGFR/ALK-negative/unknown patients. No significant difference was found in EGFR/ALK-positive patients (28.3 months, 19.1-37.5; 33.3 months, 28.1-38.5). Patients in the EGFR/ALK-negative/unknown cohort treated with first-line pemetrexed with platinum (PP) (15.8 months, 14.0-17.6, p<0.001) had longer mOS than those received non-PP regimens (13.1 months, 11.6-14.6). However, no difference was observed among EGFR/ALK-positive patients who were treated with tyrosine kinase inhibitors (TKIs) (29.5 months, 21.1-37.9; p = 0.140), PP (27.2 months, 21.6-32.8) and non-PP regimens (25.0 months, 16.0-34.0). Conclusions Our study confirmed that the use of SM+BLT is associated with superior mOS than those treated with SM only and BLT only. SM+DBR might be a better radiotherapeutic strategy for this patient population. EGFR/ALK-negative/unknown patients showed a survival benefit with PP treatment.