Objective To systematically evaluate the efficacy and safety of a combination regimen of PD-1/PD-L1 immune checkpoint inhibitors in the first-line treatment of advanced non-small cell lung cancer. Methods Randomized controlled trials (RCTs) of PD-1/PD-L1 inhibitor combination regimen in the first-line treatment of advanced non-squamous NSCLC were systematically retrieved from the Chinese and English electronic databases from inception to September 2023. The combination regimen includes PD-1/PD-L1 inhibitor+chemotherapy, PD-1/PD-L1 inhibitor+chemotherapy+anti-angiogenic agents (bevacizumab), and PD-1/PD-L1 inhibitor+CTLA4 inhibitor (ipilimumab). The network meta-analysis was performed using StataMP16.0 and R4.2.0 software. ResultsA total of 13 RCTs were collected, including 7 764 patients. In terms of effectiveness, compared with chemotherapy, several regimens improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Among them, toripalimab (Tor) plus chemotherapy (CT) may be associated with the best OS, and nivolumab plus bevacizumab and chemotherapy (Niv+Bev+CT) may provide the best PFS. Pembrolizumab (Pem) combined with CT was associated with the best treatment regimen for improving ORR. In terms of safety, except sintilimab (Sin) and Pem, the incidence of grade≥3 adverse events of all treatment regimens was significantly higher than that of chemotherapy (P<0.05). The incidence of AEs≥3 grade in Cam+CT was higher than that in Sin+CT (OR=0.44, 95%CI 0.25-0.80) and Pem+CT (OR=0.52, 95%CI 0.31-0.88). And the incidence of ≥3grade AEs in Atezolizumab (Ate) +Bev+CT (OR=2.32, 95%CI 1.14-4.71; OR=1.97, 95%CI 1.02-3.79) was also higher than that in Sin+CT and Pem+CT (P<0.05). Conclusion In non-squamous NSCLC patients, PD-1 inhibitor combined with chemotherapy can bring more benefits to advanced NSCLC patients than chemotherapy alone.
Objective To investigate the effects of growth differentiation factor 15 (GDF15) on lung adenocarcinoma bone metastasis in nude mice by regulating phosphatase and tensin homology/phosphatidylinositol 3 kinase/protein kinase B (PTEN/PI3K/AKT) signaling pathway. Methods The bone metastasis model of lung adenocarcinoma in nude mice was established and mice were randomly divided into Control group, sh-NC group, sh-GDF15 group, sh-GDF15+sh-NC group and sh-GDF15+sh-PTEN group. The changes of 50% pain withdrawl threshold (PWT) and thermal withdrawal latency (TWL) were observed. bone destruction was analyzed by Micro-CT. Bone morphology was observed by HE staining. The expression of osteoclast-related factors was detected by immunohistochemistry. The expression of PTEN/PI3K/AKT signaling pathway was detected by Western blot. Results The tibia tissue of nude mice in Control group and sh-NC group was destroyed, the continuity of bone cortex was interrupted, obvious bone tumor lesions were observed, the tumor cells were irregular in shape, densely distributed and disordered, and the nuclei were obviously deformed. Compared with sh-NC group, sh-GDF15 group had less tibial tissue destruction, the bone tumor cell density was significantly reduced, the pathological morphology was significantly improved, and 50% PWT, TWL, bone mineral density (BMD), trabecular bone volume/total volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th) and PTEN expression were increased, the expressions of trabecular separation (Tb.Sp), cathepsin K (CTSK), matrix metalloproteinase 9 (MMP-9), p-PI3K PI3K and p-Akt/Akt were decreased (P<0.05). Compared with sh-GDF15+sh-NC group, sh-GDF15+sh-PTEN group had severe tibial tissue damage, the bone tissue tumor cells were dense and the pathological injury was aggravated, and 50%PWT, TWL, BMD, BV/TV, Tb.N, Tb.Th and PTEN expression were decreased, the expressions of Tb.Sp, CTSK, MMP-9, p-PI3K /PI3K and p-Akt /Akt were increased (P<0.05). Conclusion GDF15 can promote bone metastasis of lung adenocarcinoma in nude mice, and its mechanism is related to inhibition of PTEN/PI3K/AKT signaling pathway.