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 ...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.展开更多
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 ...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.展开更多
基金supported by the National Key Research and Development Program of China(Grant No.2020YFA0803700)the National Natural Science Foundation of China(Grant Nos.91639108,81770272,and 81970425)+1 种基金the Beijing Natural Science Foundation(Grant No.7212044)the Beijing Hospital Authority Youth Program(Grant No.QML20190306)。
文摘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.
基金This work was financially supported by National Natural Science Foundation of China(Grant No.51973018,51773018)Fundamental Research Funds for the Central Universities(FRF-TP-17-001A2)Beijing Municipal Science and Technology Commission Projects(No.Z191100002019017).
文摘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.
