BackgroundUV-irradiated keratinocytes secrete various proinflammatory cytokines. UV-induced skin damage is mediated by growth factors and proinflammatory cytokines such as granulocyte macrophage colony stimulating factor (GM-CSF). In a previous study, we found that the saponin of Korean Red Ginseng (SKRG) decreased the expression of GM-CSF in UVB-irradiated SP-1 keratinocytes. In this study, we attempted to find the inhibitory mechanism of SKRG on UVB-induced GM-CSF expression in SP-1 keratinocytes.MethodsWe investigated the inhibitory mechanism of SKRG and ginsenosides from Panax ginseng on UVB-induced GM-CSF expression in SP-1 keratinocytes.ResultsTreatment with SKRG decreased the expression of GM-CSF mRNA and protein induced by irradiation of UVB in SP-1 keratinocytes. The phosphorylation of ERK was induced by UVB at 10 min, and decreased with SKRG treatment in SP-1 keratinocytes. In addition, treatment with SKRG inhibited the UVB-induced phosphorylation of epidermal growth factor receptor (EGFR), which is known to be an upstream signal of ERK. From these results, we found that the inhibition of GM-CSF expression by SKRG was derived from the decreased phosphorylation of EGFR. To identify the specific compound composing SKRG, we tested fifteen kinds of ginsenosides. Among these compounds, ginsenoside-Rh3 decreased the expression of GM-CSF protein and mRNA in SP-1 keratinocytes.ConclusionTaken together, we found that treatment with SKRG decreased the phosphorylation of EGFR and ERK in UVB-irradiated SP-1 keratinocytes and subsequently inhibited the expression of GM-CSF. Furthermore, we identified ginsenoside-Rh3 as the active saponin in Korean Red Ginseng.

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PURPOSE Lazertinib is a potent, central nervous system (CNS)–penetrant, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). This global, phase 3 study (LASER301) compared lazertinib versus gefitinib in treatment-naïve patients with EGFR-mutated (exon 19 deletion [ex19del]/L858R) locally advanced or metastatic non-small cell lung cancer (NSCLC). METHODS Patients were ≥18 years with no prior systemic anti-cancer therapy. Neurologically stable patients with CNS metastases were allowed. Patients were randomized 1:1 to lazertinib 240 mg once daily (qd) orally (po) or gefitinib 250 mg qd po, stratified by mutation status and race. The primary endpoint was investigator-assessed progression-free survival (PFS) by RECIST v1.1. RESULTS Overall, 393 patients received double-blind study treatment across 96 sites in 13 countries. Median PFS was significantly longer with lazertinib than with gefitinib (20.6 vs 9.7 months; hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.34 to 0.58; P<0.001). The PFS benefit of lazertinib over gefitinib was consistent across all predefined subgroups. The objective response rate was 76% in both groups (odds ratio, 0.99; 95% CI, 0.62 to 1.59). Median duration of response was 19.4 months (95% CI, 16.6 to 24.9) with lazertinib versus 8.3 months (95% CI, 6.9 to 10.9) with gefitinib. Overall survival data were immature at the interim analysis (29% maturity). The 18-month survival rate was 80% with lazertinib and 72% with gefitinib (HR, 0.74; 95% CI, 0.51 to 1.08; P=0.116). Observed safety of both treatments was consistent with their previously reported safety profiles. CONCLUSION Lazertinib demonstrated significant efficacy improvement compared with gefitinib in the first-line treatment of EGFR-mutated advanced NSCLC, with a manageable safety profile.

Objective: To evaluate the bioequivalence of a gliclazide/metformin combination tablet (at dose of 80/500 mg) with co-administration of metformin (500 mg) and gliclazide (80 mg) as individual tablets in healthy male Korean volunteers. Subjects, materials and methods: The study was conducted as an open-label, randomized, 2-period crossover design in 32 healthy male Korean volunteers who received a combination tablet of gliclazide/metformin at a dose of 80/500 mg or co-administration of gliclazide and metformin as individual tablets in each study period. There was a 7-day washout period between doses. Serum concentrations of gliclazide and metformin up to 32 hours after administration were determined using a validated HPLC method with UV detection. The pharmacokinetic parameters such as AUC 0-t (the area under the curve from zero to the time), AUC 0-¥ (the area under the curve from zero to infinity), C max (maximum serum concentration), t max (time to reach C max ) and t 1/2 (terminal half-life), were analyzed by noncompartmental analysis. Analysis of variance (ANOVA) was carried out using logarithmically transformed AUC 0-t , AUC 0-¥ and C max , and untransformed t max . In addition, blood glucose concentration was also logarithmically transformed and analyzed. Tolerability and safety profiles were also investigated. Results: There were no significant differences between the single combination tablet and the individual tablets in AUC 0-t , AUC 0-¥ , C max and blood glucose concentration. The point estimates (90% confidence intervals) for AUC 0-t , AUC 0-¥ and C max were 1.0293 (0.9476 -1.1178), 1.0253 (0.9185 -1.1443) and 1.0425 (0.9986 -1.0883) for gliclazide, and 0.9887 (0.9137 -1.0697), 0.9915 (0.9189 -1.0697) and 0.9882 (0.9295 -1.0505) for