Angiogenesis in hepatocellular carcinoma:mechanisms and anti-angiogenic therapies

Hepatocellular carcinoma(HCC)is the fourth leading cause of cancer-associated death worldwide.Angiogenesis,the process of formation of new blood vessels,is required for cancer cells to obtain nutrients and oxygen.HCC is a typical hypervascular solid tumor with an aberrant vascular network and angiogenesis that contribute to its growth,progression,invasion,and metastasis.Current anti-angiogenic therapies target mainly tyrosine kinases,vascular endothelial growth factor receptor(VEGFR),and plateletderived growth factor receptor(PDGFR),and are considered effective strategies for HCC,particularly advanced HCC.However,because the survival benefits conferred by these anti-angiogenic therapies are modest,new anti-angiogenic targets must be identified.Several recent studies have determined the underlying molecular mechanisms,including pro-angiogenic factors secreted by HCC cells,the tumor microenvironment,and cancer stem cells.In this review,we summarize the roles of pro-angiogenic factors;the involvement of endothelial cells,hepatic stellate cells,tumor-associated macrophages,and tumor-associated neutrophils present in the tumor microenvironment;and the regulatory influence of cancer stem cells on angiogenesis in HCC.Furthermore,we discuss some of the clinically approved anti-angiogenic therapies and potential novel therapeutic targets for angiogenesis in HCC.A better understanding of the mechanisms underlying angiogenesis may lead to the development of more optimized anti-angiogenic treatment modalities for HCC.

A novel bioactive polyurethane with controlled degradation and L-Arg release used as strong adhesive tissue patch for hemostasis and promoting wound healing

Effective strategy of hemostasis and promoting angiogenesis are becoming increasingly urgent in modern medicine due to millions of deaths caused by tissue damage and inflammation. The tissue adhesive has been favored as an optimistic and efficient path to stop bleeding, while, current adhesive presents limitations on wound care or potential degradation safety in clinical practice. Therefore, it is of great clinical significance to construct multifunctional wound adhesive to address the issues. Based on pro-angiogenic property of L-Arginine (L-Arg), in this study, the novel tissue adhesive (G-DLPUs) constructed by L-Arg-based degradable polyurethane (DLPU) and GelMA were prepared for wound care. After systematic characterization, we found that the G-DLPUs were endowed with excellent capability in shape-adaptive adhesion. Moreover, the L-Arg released and the generation of NO during degradation were verified which would enhance wound healing. Following the in vivo biocompatibility was verified, the hemostatic effect of the damaged organ was tested using a rat liver hemor-rhage model, from which reveals that the G-DLPUs can reduce liver bleeding by nearly 75% and no obvious inflammatory cells observed around the tissue. Moreover, the wound care effect was confirmed in a mouse full-thickness skin defect model, showing that the hydrogel adhesive significantly improves the thickness of newly formed dermis and enhance vascularization (CD31 staining). In summary, the G-DLPUs are promising candidate to act as multifunctional wound care adhesive for both damaged organ and trauma.