Hepatitis B–associated hepatocellular carcinoma (HCC) is often accompanied by severe vascular invasion and portal vein tumor thrombus, leading to a poor prognosis. However, the underlying mechanism of this disease remains obscure. In this study, we demonstrate that the hepatitis B virus (HBV)–encoded gene HBx induces high IL8 production through MEK–ERK signal activation, leading to enhanced endothelial permeability to facilitate tumor vascular invasion. In a vascular metastatic model using a tail vein injection in a transgenic mouse with selective expression of human CXCR1 in the endothelium, activation of the IL8–CXCR1 cascade by overexpression of IL8 in tumor cells dramatically enhanced liver metastasis. Mechanistically, IL8 selectively induced GARP-latent-TGFβ in liver sinusoidal endothelial cells and subsequently provoked preferential regulatory T-cell polarization to suppress antitumor immunity. Collectively, these findings reveal a hepatitis B–associated IL8–CXCR1 signaling axis that mediates vascular invasion and local microenvironmental immune escape of HCC to induce intrahepatic metastasis, which may serve as potential therapeutic targets for HBV-associated HCC. Significance: This study identifies a hepatitis B–induced IL8/CXCR1/TGFβ signaling cascade that suppresses antitumor immunity and enhances metastasis in hepatocellular carcinoma, providing new potential targets for therapeutic intervention.

The Chang'e-5 mission of China is planned to be launched in 2019 to the landing area near Mons Rümker located in Oceanus Procellarum. Aiming to generate a high-resolution and high-quality digital orthophoto map (DOM) of the planned landing area for supporting the mission and various scientific analyses, this study developed a systematic and effective method for large-area seamless DOM production. The mapping results of the Chang'e-5 landing area using over 700 Lunar Reconnaissance Orbiter Camera (LROC) Narrow Angle Camera (NAC) images are presented. The resultant seamless DOM has a resolution of 1.5 m, covers a large area of 20° in longitude and 4° in latitude, and is tied to SLDEM2015. The results demonstrate that the proposed method can reduce the geometric inconsistencies among the LROC NAC images to the subpixel level and the positional errors with respect to the reference digital elevation model to about one grid cell size.

Phosphoprotein enriched in astrocytes 15 (PEA-15) plays an important role in controlling biological behaviors of cancer cells. In the present study, we demonstrated that PEA-15 was overexpressed in gastric cancer tissues and associated with tumor staging, differentiation, pathological types and the prognosis of patients. Gastric cancer cells expressed variable levels of PEA-15 and its bi-phosphorylation forms, p-PEA-15 (Ser104) and p-PEA-15 (Ser116). To gain insight into the functional role of PEA-15, we generated cells stably depleted of PEA-15 and resistant to cisplatin (CDDP) from human gastric cancer cells. PEA-15 depletion inhibited cell proliferation by reducing cyclin D1 expression through the extracellular signal-regulated kinase (ERK) pathway, resulting in cell cycle arrest at the G1 phase, and induced apoptosis by activating caspase-8. PEA-15 depletion also enhanced the inhibitory effect of CDDP that caused cell cycle arrest at the S phase and also enhanced the pro-apoptotic activity of CDDP in vitro and in animal models of tumorigenesis and therapeutic effects. PEA-15 and its phosphorylated forms were overexpressed in CDDP-resistant cells, which had higher levels of p-AKT. Specific inhibition of AKT by MK2206 reduced the expression of p-PEA-15 at the Ser116 residue, resulting in sequential downregulation of p-ERK1/2, cyclin D1 and caspase-8 activation. However, depletion of PEA-15 had little effect on AKT expression or phosphorylation, or its downstream factors including p27, glycogen synthase kinase 3β and caspase-9, indicating that the regulatory effects between PEA-15 and AKT were unidirectional. In summary, the results indicated that PEA-15 expression was associated with clinicopathology and prognosis in gastric cancer and was regulated by AKT to participate in CDDP resistance, indicating that it may be a potential target for overcoming CDDP resistance in the treatment of gastric cancer.