Abnormalities in cell cycle regulation are reported to be strongly associated with tumorigenesis and progression of tumors. Wnt/β-catenin signaling pathway and cell cycle play key roles during the genesis and development of hepatocellular carcinoma (HCC). Current studies indicated that expressions of cyclin A, E and D1 were affected after silencing of β-catenin gene in HCC, but it is unclear if other cyclins are affected. To determine the relation, small interference RNA (siRNA) against β-catenin was transfected into HCC cell lines HepG2 and SMMC-7721, and cell cycle and cyclin B1 and cyclin C protein expression were detected. Cell cycle was arrested in G0/G1 at 72h after transfection and the cell cycle began to transfer from G0/G1 to G2/M through S and had a trend to revert at 96h. In addition, β-catenin protein expression was decreased at both 72 and 96h, although the level was slightly higher at 96h than that at 72h. However, cyclin B1 expression decreased at 72h and increased at 96h, cyclin C expression increased at 72h and decreased at 96h. These findings suggest that silencing β-catenin gene may induce the changes of cell cycle and cyclin B1 and cyclin C protein expression. Wnt/β-catenin signaling pathway probably takes part in the genesis and development of HCC through regulating cell cycle and the expression of cyclin B1 and cyclin C.

Background: Pancreatic ductal adenocarcinoma (PDAC) is in urgent need of a second‐line or later‐line treatment strategy. We aimed to analyze the efficacy and safety of additional anlotinib, specifically anlotinib in combination with immunotherapy, in patients with PDAC who have failed first‐line therapy.Methods: Patients with pathological diagnosis of PDAC were additionally treated with anlotinib, and some patients were treated with anti‐PD‐1 agents at the same time, which could be retrospectively analyzed. The efficacy and safety of additional anlotinib were evaluated.Results: A total of 23 patients were included. In patients treated with additional anlotinib, the overall median progression‐free survival (PFS) was 1.8 months and the median overall survival (OS) was 6.3 months, regardless of anti‐PD‐1 agents. Among patients receiving additional anlotinib in combination with anti‐PD‐1 agents, median PFS and OS were 1.8 and 6.5 months, respectively. Adverse events (AEs) were observed in 16 patients (69.6%). In patients treated with additional anlotinib, the majority of AEs were grade 1–3. Univariate analysis revealed that patients with baseline red blood cell distribution width (RDW) <14% treated with additional anlotinib plus anti‐PD‐1 agents had significantly longer OS than patients with baseline RDW ≥14% (p = 0.025). Patients with additional anlotinib plus anti‐PD‐1 agents as second‐line therapy had a longer OS than those treated as later‐line therapy (p = 0.012). Multivariate analysis showed that baseline RDW was the only independent risk factor for OS (p = 0.042).Conclusion: The combination of anlotinib and immunotherapy represents an effective add‐on therapy with tolerable AEs as second‐ or later‐line therapy in patients with PDAC, particularly in patients with baseline RDW <14%.

Methods A retrospective study of 133 non-small cell lung cancer (NSCLC) patients treated with PD-1 inhibitors was performed. Medical records and haematological data were collected. The trends of NLR and PLR during treatment were analysed by the Mann-Whitney U test. Logistic regression was used to investigate the association of irTD, all immune-related adverse events (irAEs) with pre- and post-treatment NLR and PLR. The relationship of these predictive factors with tumour response and survival was estimated using the Chi-squared test or Kaplan‒Meier analysis. Results 30 patients (22.6%) developed irTDs. The NLR showed a significant decreasing trend during treatment. Patients with previous thyroid diseases and lower NLR_3w (NLR < 2.3) were significantly associated with irTDs. Pretreatment lower NLR and lower NLR_3w were associated with irAEs. There was no difference in tumor response between patients with and without irTDs. PFS was prolonged in patients with irTDs and with lower PLR_7w. Conclusions IrTD onset is common in patients receiving PD-1 inhibitors and is associated with prolonged PFS. The NLR_3w after receiving PD-1 inhibitors appears to be a factor for identifying NSCLC patients at high-risk of occurring irTD. Post-treatment lower PLR is associated with better PFS.