ABSTRACT
Programmed death ligand-1 (PD-L1) is a potentially important tumor immunotherapy target. However, whether PD-L1 expression is associated with survival in nasopharyngeal carcinoma (NPC) remains controversial. The aim of the present study was to investigate the association between PD-L1 expression and prognosis in NPC. The expression of PD-L1 was assessed in tumor specimens from 120 patients with NPC using immunohistochemistry. Staining was evaluated using the H-score method. The associations between PD-L1 expression and clinical characteristics and prognosis were analyzed. Overall, 78% of the patients had stage I-III and 22% had stage IV disease. The estimated 5-year overall survival (OS) and disease-free survival (DFS) rates for the entire cohort were 87.5 and 70.1%, respectively. PD-L1 expression was detected in 85 (71%) patients and was localized to the tumor cells. High tumor expression of PD-L1 (median H-score ≥5) was associated with significantly poorer OS (P=0.023) and DFS (P=0.002). Univariate analysis indicated that low PD-L1 expression was associated with better DFS compared with high PD-L1 expression (HR=0.163, 95% CI: 0.044-0.600, P=0.006 for DFS). Multivariate analysis revealed that T stage (HR=8.190, 95% CI: 1.355-18.152; P=0.023) and PD-L1 expression level (HR=0.124, 95% CI: 0.031-0.509; P=0.001) served as independent prognostic factors for DFS. In conclusion, tumor PD-L1 expression was found to be a significant prognostic factor in NPC, and high PD-L1 expression may be of prognostic value for recurrence and metastasis following conventional treatments.
ABSTRACT
Lipoxins (LXs) display unique pro-resolving and anti-inflammatory functions in a variety of inflammatory conditions. The present study was undertaken to investigate the effects of BML-111 (5(S),6(R),7-trihydroxyheptanoic acid methyl ester), the agonist of lipoxin A4 receptor, in a model of Lipopolysaccharides (LPS) and d-Galactosamine (d-GalN) induced acute liver injury, and to explore the mechanisms. Histopathological analyses were carried out to quantify liver injury degree. The activities of myeloperoxidase (MPO) were examined to evaluate the levels of neutrophil infiltration. The activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum were detected to evaluate the functions of the liver. The amounts of tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), and interleukin-1ß (IL-1ß) were measured using enzyme-linked immunosorbent assay (ELISA), and the expression levels of transforming growth factor-ß1(TGF-ß1) and cyclooxygenase-2 (COX-2) were examined using Western blotting. The antioxidant capacity, the activities of inducible nitric oxide synthase (iNOS), the contents of malondialdehyde (MDA) and nitric oxide (NO) were analyzed with the kits via biochemical analysis. We established the model of acute liver injury with lipopolysaccharide and d-Galactosamine (LPS/d-GalN): (1) histopathological results and MPO activities, with the activities of AST and ALT in serum, consistently demonstrated LPS and d-GalN challenge could cause severe liver damage, but BML-111 could prevent pathological changes, inhibit neutrophil infiltration, and improve the hepatic function; (2) LPS/d-GalN increased TNF-α, IL-1ß, COX-2, and IL-10, while decreasing TGF-ß1. However, BML-111 could repress LPS/d-GalN -induced TNF-α, IL-1ß and COX-2, meanwhile increasing the expression levels of TGF-ß1 and IL-10; (3) LPS/d-GalN inhibited the activities of superoxide dismutase (SOD), catalase (CAT), total antioxidant capacity (T-AOC), and hydroxyl radical-scavenging ability, simultaneously increasing the levels of MDA and NO, so also the activity of iNOS. Otherwise, BML-111 could reverse all the phenomena. In a word, BML-111 played a protective role in acute liver injury induced by LPS and d-GalN in rats, through improving antioxidant capacity and regulating the balance of inflammatory cytokines.
