Background: Drug-induced liver injury (DILI) is a common adverse event, which compromises the safety of numerous drugs, poses a significant risk to patient health, and enhances healthcare expenditures. Many articles have been recently published on DILI related research, though no relevant scientometric study has been published yet. This scientometric study was aimed at comprehensively analyzing the knowledge base and emerging topics on DILI.

Elevated platelets based inflammatory indices, especially APRI, was associated with adverse characteristic features and poor prognosis in HCC, especially for patients with HBV infection or cirrhosis. Antiplatelet treatment may represent a potential therapy for HBV-induced HCC recurrence.

Tumor cells co-express vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFRs) that interact each other to support a self-sustainable cell growth. So far, this autocrine VEGF loop is not reported in human intrahepatic cholangiocarcinoma (ICC). Apatinib is a highly selective VEGFR2 inhibitor, but its effects on ICC have not been investigated. In this study, we reported that VEGF and phosphorylated VEGFR2 were expressed at a significantly high level in ICC patient tissues (P<0.05). In vitro, treating ICC cell lines RBE and SSP25 with recombinant human VEGF (rhVEGF) induced phosphorylation of VEGFR1 (pVEGFR1) and VEGFR2 (pVEGFR2); however, only the VEGFR2 played a role in the anti-apoptotic cell growth through activating a PI3K-AKT-mTOR anti-apoptotic signaling pathway which generated more VEGF to enter this autocrine loop. Apatinib inhibited the anti-apoptosis induced by VEGF signaling, and promoted cell death in vitro. In addition, Apatinib treatment delayed xenograft tumor growth in vivo. In conclusion, the autocrine VEGF/VEGFR2 signaling promotes ICC cell survival. Apatinib inhibits anti-apoptotic cell growth through suppressing the autocrine VEGF signaling, supporting a potential role for using Apatinib in the treatment of ICC.

Purpose gp96 (grp94) is a key downstream chaperone in the ER to mediate unfolded protein response (UPR) and the pathogenesis of multiple myeloma (MM) is closely linked to dysregulated UPR. In this study, we aimed to determine the roles of gp96 in the initiation and progression of MM in vivo and in vitro. Experimental design We generated a mouse model with over-expression of XBP1s and conditional deletion of gp96 in B cell compartment simultaneously to identify the roles of gp96 in the development of MM in vivo. Using a shRNA system, we silenced gp96 in multiple human MM cells and examined the effect of gp96 knockdown on MM cells by cell proliferation, cell cycle analysis, apoptosis assay, immunohistochemistry and human myeloma xenograft model. The anti-cancer activity of gp96 selective inhibitor, WS13 was evaluated by apoptosis assay and MTT assay. Results Genetic deletion of gp96 in XBP1s-Tg mice attenuates multiple myeloma. Silencing of gp96 causes severe compromise in human MM cell growth through inhibiting Wnt-LRP-survivin pathway. We also confirmed that knockdown of gp96 decreased human MM growth in a murine xenograft model. The targeted gp96 inhibitor induced apoptosis and blocked MM cell growth, but did not induce apoptosis in pre-B leukemic cells. We have demonstrated that myeloma growth is dependent on gp96 both genetically and pharmacologically. Conclusions gp96 is essential for MM cell proliferation and survival, suggesting that gp96 is a novel therapeutic target for multiple myeloma.