Wnt family member 5a (Wnt5a) is a noncanonical member of the Wnt family that is highly expressed in atherosclerosis. Studies have shown that Wnt5a/receptor tyrosine kinase-like orphan receptors 2 (ror2) signaling can participate in the formation of foam cells; however, the role of ror2 in vascular endothelial cells during atherosclerotic injury is unknown. Therefore, the present study aimed to investigate the role of ror2 in tumor necrosis factor (TnF)-α-induced vascular endothelial cell injury and investigate whether it could be regulated by Wnt5a. Human umbilical vein endothelial cells were transfected with short hairpin RNA specific against ror2 in the absence or presence of TnF-α. The alteration of inflammatory cytokine levels was detected, and the expression of adhesion molecules was assessed. Western blot and flow cytometry analyses were used to detect the activation of nuclear factor-κB (nF-κB) signaling and cell apoptosis. The interaction between ror2 and Wnt5a was confirmed by immunoprecipitation. ror2 was upregulated upon TnF-α stimulation. Knockdown of ror2 inhibited the TnF-α-induced release of inflammatory cytokines, the expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 and the activation of nF-κB signaling. Furthermore, cell apoptosis induced by TnF-α was rescued by ror2 silencing. in addition, Wnt5a expression was increased by TnF-α, and ror2 could bind to Wnt5a, the knockdown of which could downregulate the levels of ror2. in conclusion, it was demonstrated that ror2 was upregulated upon TnF-α stimuli, and interference of ror2 regulated by Wnt5a could suppress TnF-α-induced inflammation and apoptosis in vascular endothelial cells.

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e16176 Background: The earlier randomized phase III RESORCE trial and several real-world studies demonstrate that regorafenib improves overall survival (OS) in advanced hepatocellular carcinoma (HCC). This study aims to evaluate the efficacy and safety of regorafenib alone or in combinations in advanced HCC. Methods: 60 Patients with pathologically or clinically diagnosed advanced HCC were enrolled. We retrospectively analyzed the efficacy and safety of patients who received at least one cycle of regorafenib between March 7, 2019 and December 25, 2022 in the Affiliated Hospital of Nantong University and Nantong Third People's Hospital. The primary endpoints were objective response rate (ORR) and progression free survival (PFS). The secondary endpoints were overall survival (OS), disease control rate (DCR), and safety. The safety and efficacy were assessed by investigators per CTCAE v5.0 and mRECIST v1.1, respectively. Data on survival rates were calculated using the Kaplan-Meier method. Results: The average age was 62.63 years, and 95% were male. Most patients had a Child-Pugh A score (73.3%), and the proportion of patients with BCLC stage B and C classes were 41.7% and 58.3%, respectively. 3 (5%) patients received single-drug regorafenib therapy, and the remaining patients (95%) received different combination therapies, including regorafenib plus immune checkpoint inhibitors (ICIs) (10%), regorafenib combined with TACE (40%), and triple therapy (TKI, ICI, TACE) (45%). The ORR and DCR were 40% and 92%, respectively. With a median follow-up of 16.10 months (95%CI, 11.067-21.133), the median PFS was 8.4 months (95% CI, 5.597-11.203), and the median OS has not been reached. Most patients tolerated 120mg or 160mg once daily during weeks 1–3 of each 4-week cycle. 23 patients (38.33%) experienced adverse events (AEs). The most frequent AE (≥5%) included hand-foot syndrome (23.33%), diarrhea (11.67%), and fatigue (6.77%). The incidence of grade 3 AE was 3%. No grade 4 AE and new safety signals were identified. Conclusions: Regorafenib alone or in combination had a manageable safety profile and promising efficacy in advanced HCC patients.