ABSTRACT
The effect of anti-programmed cell death 1 (anti-PD-1) immunotherapy is limited in patients with hepatocellular carcinoma (HCC). Yes-associated protein 1 (YAP1) expression increased in liver tumor cells in early HCC, and Akkermansia muciniphila abundance decreased in the colon. The response to anti-PD-1 treatment is associated with A. muciniphila abundance in many tumors. However, the interaction between A. muciniphila abundance and YAP1 expression remains unclear in HCC. Here, anti-PD-1 treatment decreased A. muciniphila abundance in the colon, but increased YAP1 expression in the tumor cells by mice with liver tumors in situ. Mechanistically, hepatocyte-specific Yap1 knockout (Yap1LKO) maintained bile acid homeostasis in the liver, resulting in an increased abundance of A. muciniphila in the colon. Yap1 knockout enhanced anti-PD-1 efficacy. Therefore, YAP1 inhibition is a potential target for increasing A. muciniphila abundance to promote anti-PD-1 efficacy in liver tumors. Dihydroartemisinin (DHA), acting as YAP1 inhibitor, increased A. muciniphila abundance to sensitize anti-PD-1 therapy. A. muciniphila by gavage increased the number and activation of CD8+ T cells in liver tumor niches during DHA treatment or combination with anti-PD-1. Our findings suggested that the combination anti-PD-1 with DHA is an effective strategy for liver tumor treatment.
ABSTRACT
Objective To investigate the effect of SABP, a water-soluble component of Salvia miltiorrhiza, on the growth of orthotopic transplantation of H22 liver cancer and the immune microenvironment of liver cancer. Methods We established a mouse model of orthotopic transplantation of H22 cell liver cancer in BALB/c mice. ELISA was used to detect the expression of PD-L1, TGF-β, IL-1β, IL-10, IL-4, IFN-γ, IL-18, IL-7, IL-2, CCL-2 and CCL-21 in the liver. We counted the organ indexes of liver, spleen and kidney. Results SABP inhibited the growth of orthotopic transplantation tumors of H22 cell liver cancer, and increased the expression levels of PD-L1, TGF-β, IL-1β and IL-10 in the microenvironment of liver cancer, as well as the liver, spleen and kidney coefficients. Conclusion SABP could inhibit the growth of orthotopic transplantation tumors of H22 cell liver cancer and promote the expression of PD-L1, TGF-β, IL-1β and IL-10 in the microenvironment of liver cancer.
ABSTRACT
Objective To study the application of pulmonary angiography and reconstruction techniques with 16-detector row spiral CT in the diagnosis of pulmonary embolism (PE) in the elderly.Methods Twenty-four elderly patients with suspected pulmonary thromboembolism received detection of CT and pulmonary artery angiography ( CTPA ) on 16-detector MSCT.Post-reconstruction techniques included maximum intensity projection (MIP), volume rendering (VR)and multiple planar reformation (MPR). Results A total of 161 pulmonary artery thrombi were detected in 24 elderly patients. The direct signs of pulmonary embolism included total occlusion (16.8%, 27/161), partial filling defect (67.7%, 109/161) and central filling defect or track sign (15.5%, 25/161). A total of 161 pieces of pulmonary thrombi were detected in transect image, 153 (95.0%) in MPR, 113 (70.2%) in MIP and 69 (42.9%) in VR. The transect image excelled evidently MIP and VR image in displaying pulmonary thrombi, especially the thrombi in pulmonary lobe and pulmonary artery branch (χ2 =235.36 and 243.41, P＜0.05). Conclusions The 16-detector row spiral CT pulmonary angiography is non-invasive, fast and high sensitive, it should be the first choice for the diagnosis of PE in the elderly.