Inhibition of PD-L1 expression in non-small cell lung cancer may reduce vasculogenic mimicry formation by inhibiting the epithelial mesenchymal transformation process.

Non-small cell lung cancer (NSCLC) is a kind of highly malignant tumor. Studies have shown that Vasculogenic mimicry (VM) may be responsible for dismal prognosis in NSCLC. Immunotherapy with programmed death-1 (PD-1) or programmed death ligand-1 (PD-L1) has significantly altered the treatment of assorted cancers, including NSCLC, but its role and mechanism in the formation of Vasculogenic mimicry (VM) in NSCLC remains unclear. This study aimed to investigate the role of the anti-PD-L1 antibody in the formation of VM in NSCLC and its possible mechanisms. The results showed that anti-PD-L1 antibody therapy could inhibit the growth of NSCLC-transplanted tumors and reduce the formation of VMs. In addition, this study found that anti-PD-L1 antibodies could increase the expression of the epithelial-mesenchymal transition (EMT) related factor E-cadherin. zinc finger E-box binding homeobox 1 (ZEB1) is an important transcription factor regulating EMT. Knocking down ZEB1 could significantly inhibit tumor growth, as well as the expression of VE-cadherin and mmp2, while remarkably increase the expression of E-cadherin. During this process, the formation of VM was inhibited by knowing down ZEB1 in both in vitro and in vivo experiments of the constructed ZEB1 knockdown stable transfected cell strains. Therefore, in this study, we found that anti-PD-L1 antibodies may reduce the formation of VMs by inhibiting the EMT process.

Expression of Formin-like 2 and cortactin in gallbladder adenocarcinoma and their clinical significance.

OBJECTIVE: To investigate the expressions of Formin-like 2 (FMNL2) and Cortactin (CTTN) in gallbladder adenocarcinoma (GBAC) and their associations with the clinicopathological characteristics of the patients. METHODS: The expressions of FMNL2 and CTTN were detected with immunohistochemistry (Max Vision) in 105 GBAC tissues and 40 normal gallbladder tissues. RESULTS: The positive expression rates of FMNL2 and CTTN in normal gallbladder tissues were 25% and 20%, different from the positive expression rates of 84.76% and 86.67% in GBAC tissues (P < 0.001). The positive expression rate of FMNL2 and CTTN in GBAC correlated with tumor differentiation, tumor-node-metastasis (TNM), lymph node metastasis (LNM), and distant metastasis. FMNL2 expression was positively correlated with CTTN expression. Kaplan-Meier analysis showed that the overall survival time of patients with positive expressions group of FMNL2 and CTTN was significantly shorter than that of the negative expression group. Cox multivariate analysis showed that TNM, LNM, distant metastasis, and positive expression of FMNL2 and CTTN were independent factors influencing the prognosis of patients with GBAC (P < 0.05). CONCLUSION: The positive expression of FMNL2 and CTTN in GBAC is significantly increased, which may be related to the occurrence and development of GBAC. The combined detection of FMNL2 and CTTN may provide a scientific theoretical basis for the early diagnosis of GBAC, the development of new antitumor drugs, and the search for new targets of biotherapy.