RESUMO
BACKGROUND: Although the current conventional treatment strategies for esophageal carcinoma (EC) have been proven effective, they are often accompanied by serious adverse events. Therefore, it is still necessary to continue to explore new therapeutic strategies for EC to improve the clinical outcome of patients. AIM: To elucidate the clinical efficacy of concurrent chemoradiotherapy (CCRT) with thalidomide (THAL) and S-1 (tegafur, gimeracil, and oteracil potassium capsules) in the treatment of EC as well as its influence on serum tumor markers (STMs). METHODS: First, 62 patients with EC treated at the Zibo 148 Hospital between November 2019 and November 2022 were selected and grouped according to the received treatment. Among these, 30 patients undergoing CCRT with cis-platinum and 5-fluorouracil were assigned to the control group (Con), and 32 patients receiving CCRT with THAL and S-1 were assigned to the research group (Res). Second, inter-group comparisons were carried out with respect to curative efficacy, incidence of drug toxicities, STMs [carbohydrate antigen 125 (CA125) and macrophage inflammatory protein-3α (MIP-3α)], angiogenesis-related indicators [vascular endothelial growth factor (VEGF); VEGF receptor-1 (VEGFR-1); basic fibroblast growth factor (bFGF); angiogenin-2 (Ang-2)], and quality of life (QoL) [QoL core 30 (QLQ-C30)] after one month of treatment. RESULTS: The analysis showed no statistical difference in the overall response rate and disease control rate between the two patient cohorts; however, the incidences of grade I-II myelosuppression and gastrointestinal reactions were significantly lower in the Res than in the Con. Besides, the post-treatment CA125, MIP-3α, VEGF, VEGFR-1, bFGF, and Ang-2 Levels in the Res were markedly lower compared with the pre-treatment levels and the corresponding post-treatment levels in the Con. Furthermore, more evident improvements in QLQ-C30 scores from the dimensions of physical, role, emotional, and social functions were determined in the Res. CONCLUSION: The above results demonstrate the effectiveness of THAL + S-1 CCRT for EC, which contributes to mild side effects and significant reduction of CA125, MIP-3α, VEGF, VEGFR-1, bFGF, and Ang-2 Levels, thus inhibiting tumors from malignant progression and enhancing patients' QoL.
RESUMO
Macrophages play crucial roles in immune response and atherosclerosis-related cardiovascular disease. Recent evidence of macrophage autophagy has demonstrated a novel pathway through which contributes to vascular inflammation. The aim of this study was to elucidate the role of autophagy in the inhibition of inflammatory response in macrophages by atorvastatin. We found that atorvastatin promoted autophagy flow determined by up-regulating the expression of autophagy-related protein microtubule-associated protein light chain (LC3B), inducing the formation of autophagosomes and down-regulating the expression of SQSTM1/P62, which is consumed during autophagy. Atorvastatin also inhibited the expression of inflammatory factors IL-1ß and TNFα induced by LPS in RAW264.7 cells. Furthermore, pretreatment with an autophagy inhibitor 3MA or LY294002 attenuated the suppressive effect of atorvastatin on LPS-induced IL-1ß and TNFα expression. Additionally, knockdown autophagy-related gene 5(Atg5) with a special siRNA also prevented the role of atorvastatin in decreasing IL-1ß and TNFα release induced by LPS. Finally, we detected that AKT/mTOR/P70S6K signaling pathway was involved in atorvastatin-induced autophagy in macrophages. These data suggest that atorvastatin attenuates LPS-induced inflammatory factors secretion, at least in part, through enhancing autophagy by AKT/mTOR signaling pathway. Our findings provide a novel evidence that statins exert anti-inflammatory effect in atherosclerosis by autophagy activation.