ABSTRACT
Introduction: The available approved anticancer drugs for Chinese patients are relatively limited because of China's low participation rate in international clinical trials. Therefore, a focus on approved anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) drugs in China is needed. This study aims to assess the heterogeneity of anti-PD-1/PD-L1 antibodies manufactured in China (domestic PD-1/PD-L1) and overseas (imported PD-1/PD-L1) when combined with chemotherapy as the first-line treatment of NSCLC. Methods: A systematic search was performed using PubMed, EMBASE, and Cochrane Library of publications up to July 13, 2023. Meta-analysis was applied to compare the efficacy and safety profile between anti-PD-1/PD-L1 antibodies plus chemotherapy (PD-1/PD-L1+Chemo) and chemotherapy alone using STATA software. Pooled hazard ratios for progression-free survival and overall survival, odds ratios for objective response rate, and incidence rate of grade greater than or equal to three treatment-related adverse events with 95% confidence intervals were calculated in the domestic group and imported group by a random-effects model, and the heterogeneity between the two estimates was assessed. Results: There were 14 eligible clinical studies with a total of 3951 patients involved in this analysis, including eight studies of domestic PD-1/PD-L1+Chemo and six studies of imported PD-1/PD-L1+Chemo. The study revealed that there was no significant difference between domestic and imported PD-1/PD-L1+Chemo in overall survival (p = 0.80), progression-free survival (p = 0.53), and incidence rate of grade greater than or equal to three treatment-related adverse events (p = 0.10). Nevertheless, the objective response rate of imported PD-1/PD-L1+Chemo was significantly higher than that of domestic PD-1/PD-L1+Chemo (p = 0.03). Conclusions: Domestic anti-PD-1/PD-L1 antibodies plus chemotherapy were found to have comparable efficacy and safety to those combined with imported anti-PD-1/PD-L1 antibodies based on current evidence.
ABSTRACT
OBJECTIVE: To explore the mechanism of miR-195-5p in the pathogenesis non-small cell lung cancer (NSCLC) and cisplatin resistance. METHODS: The function of miR-195-5p in NSCLC and cisplatin resistance were determined by MTT, scratch assay, transwell assay, and nude mice xenograft experiments. miR-195-5p target gene was identified by dual-luciferase reporter assays and real-time PCR analysis. RESULTS: miR-195-5p content was lower in A549/DDP than that in A549 cells, with reduced chemotherapy sensitivity and increased cell invasion and migration ability. The loss-of-function and gain-of-function assays illustrated that miR-195-5p might have increased the chemosensitivity to cisplatin in the A549/DDP cells and decreased cell migration and invasion. FGF2 is a negatively correlated action target of miR-195-5p. miR-195-5p might affect EMT by inhibiting FGF2. Overexpression of FGF2 resulted in enhanced cisplatin resistance in the cells, while miR-195-5p might have reversed this resistance. CONCLUSION: Overall, miR-195-5p might target FGF2 to reduce cisplatin resistance in A549/DDP cells and enhance chemosensitivity.
ABSTRACT
BACKGROUND: Acute pancreatitis (AP) is rapid-onset pancreatic inflammation that causes local and systemic inflammatory response syndrome (SIRS) with high morbidity and mortality, but no approved therapies are currently available. P-selectin glycoprotein ligand 1 (PSGL-1) is a transmembrane glycoprotein to initiate inflammatory responses. We hypothesized that PSGL-1 may be involved in the development of AP and would be a new target for the treatment of AP. AIM: To investigate the role and mechanism of PSGL-1 in the development of AP. METHODS: The PSGL-1 expression on leukocytes was detected in peripheral blood of AP patients and volunteers. Pancreatic injury, inflammatory cytokines expression, and inflammatory cell infiltration was measured in AP mouse models induced with PSGL-1 knockout (PSGL-1 -/-) and wild-type (PSGL-1 +/+) mice. Leukocyte-endothelial cell adhesion was measured in a peripheral blood mononuclear cell (PBMC)-endothelial cell coculture system. RESULTS: The expression of PSGL-1 on monocytes and neutrophils was significantly increased in AP patients. Compared with PSGL-1 +/+ mice, PSGL-1 -/- AP mice induced by caerulein exhibited lower serum amylase, less Interleukin-1beta (IL-1beta) and Interleukin-6 (IL-6) expression, less neutrophil and macrophage infiltration, and reduced peripheral neutrophil and monocyte accounts. PSGL-1 deficiency alleviated leukocyte-endothelial cell adhesion via IL-6 but not IL-1beta. CONCLUSION: PSGL-1 deficiency effectively inhibits the development of AP by preventing leukocyte-endothelial cell adhesion via IL-6 stimulation and may become a potential therapeutic target for treating AP.
