The prognosis of hepatocellular carcinoma (HCC) still remains dismal, although many advances in its clinical study have been made. It is important for tumor control to identify the factors that predispose patients to ...The prognosis of hepatocellular carcinoma (HCC) still remains dismal, although many advances in its clinical study have been made. It is important for tumor control to identify the factors that predispose patients to death. With new discoveries in cancer biology, the pathological and biological prognostic factors of HCC have been studied quite extensively. Analyzing molecular markers (biomarkers) with prognostic significance is a complementary method. A large number of molecular factors have been shown to associate with the invasiveness of HCC, and have potential prognostic significance. One important aspect is the analysis of molecular markers for the cellular malignancy phenotype. These include alterations in DNA ploidy, cellular proliferation markers (PCNA, Ki-67, Mcm2, MIB1, MIA, and CSE1L/CAS protein), nuclear morphology, the p53 gene and its related molecule MD M2, other cell cycle regulators (cyclin A, cyclin D, cyclin E, cdc2, p27, p73), oncogenes and their receptors (such as ras, c-myc, c-fms, HGF, c-met, and erb-B receptor family members), apoptosis related factors (Fas and FasL), as well as telomerase activity. Another important aspect is the analysis of molecular markers involved in the process of cancer invasion and metastasis. Adhesion molecules (E-cadherin, catenins, serum intercellular adhesion molecule-1, CD44 variants), proteinases involved in the degradation of extracellular matrix (MMP-2, MMP-9, uPA, uPAR, PAI), as well as other molecules have been regarded as biomarkers for the malignant phenotype of HCC, and are related to prognosis and therapeutic outcomes. Tumor angiogenesis is critical to both the growth and metastasis of cancers including HCC, and has drawn much attention in recent years. Many angiogenesis-related markers, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived endothelial cell growth factor (PD-ECGF), thrombospondin (TSP), angiogenin, pleiotrophin, and endostatin (ES) levels, as well as intratumor microvessel density (M展开更多
The NLRP3 inflammasome is a cytosolic multiprotein complex composed of the innate immune receptor protein NLRP3,adapter protein ASC,and inflammatory protease caspase-1 that responds to microbial infection,endogenous d...The NLRP3 inflammasome is a cytosolic multiprotein complex composed of the innate immune receptor protein NLRP3,adapter protein ASC,and inflammatory protease caspase-1 that responds to microbial infection,endogenous danger signals,and environmental stimuli.The assembled NLRP3 inflammasome can activate the protease caspase‐1 to induce gasdermin D-dependent pyroptosis and facilitate the release of IL-1β and IL-18,which contribute to innate immune defense and homeostatic maintenance.However,aberrant activation of the NLRP3 inflammasome is associated with the pathogenesis of various inflammatory diseases,such as diabetes,cancer,and Alzheimer’s disease.Recent studies have revealed that NLRP3 inflammasome activation contributes to not only pyroptosis but also other types of cell death,including apoptosis,necroptosis,and ferroptosis.In addition,various effectors of cell death have been reported to regulate NLRP3 inflammasome activation,suggesting that cell death is closely related to NLRP3 inflammasome activation.In this review,we summarize the inextricable link between NLRP3 inflammasome activation and cell death and discuss potential therapeutics that target cell death effectors in NLRP3 inflammasome-associated diseases.展开更多
Cell death is a fundamental physiological process in all living organisms.Its roles extend from embryonic development,organ maintenance,and aging to the coordination of immune responses and autoimmunity.In recent year...Cell death is a fundamental physiological process in all living organisms.Its roles extend from embryonic development,organ maintenance,and aging to the coordination of immune responses and autoimmunity.In recent years,our understanding of the mechanisms orchestrating cellular death and its consequences on immunity and homeostasis has increased substantially.Different modalities of what has become known as‘programmed cell death’have been described,and some key players in these processes have been identified.We have learned more about the intricacies that fine tune the activity of common players and ultimately shape the different types of cell death.These studies have highlighted the complex mechanisms tipping the balance between different cell fates.Here,we summarize the latest discoveries in the three most well understood modalities of cell death,namely,apoptosis,necroptosis,and pyroptosis,highlighting common and unique pathways and their effect on the surrounding cells and the organism as a whole.展开更多
文摘The prognosis of hepatocellular carcinoma (HCC) still remains dismal, although many advances in its clinical study have been made. It is important for tumor control to identify the factors that predispose patients to death. With new discoveries in cancer biology, the pathological and biological prognostic factors of HCC have been studied quite extensively. Analyzing molecular markers (biomarkers) with prognostic significance is a complementary method. A large number of molecular factors have been shown to associate with the invasiveness of HCC, and have potential prognostic significance. One important aspect is the analysis of molecular markers for the cellular malignancy phenotype. These include alterations in DNA ploidy, cellular proliferation markers (PCNA, Ki-67, Mcm2, MIB1, MIA, and CSE1L/CAS protein), nuclear morphology, the p53 gene and its related molecule MD M2, other cell cycle regulators (cyclin A, cyclin D, cyclin E, cdc2, p27, p73), oncogenes and their receptors (such as ras, c-myc, c-fms, HGF, c-met, and erb-B receptor family members), apoptosis related factors (Fas and FasL), as well as telomerase activity. Another important aspect is the analysis of molecular markers involved in the process of cancer invasion and metastasis. Adhesion molecules (E-cadherin, catenins, serum intercellular adhesion molecule-1, CD44 variants), proteinases involved in the degradation of extracellular matrix (MMP-2, MMP-9, uPA, uPAR, PAI), as well as other molecules have been regarded as biomarkers for the malignant phenotype of HCC, and are related to prognosis and therapeutic outcomes. Tumor angiogenesis is critical to both the growth and metastasis of cancers including HCC, and has drawn much attention in recent years. Many angiogenesis-related markers, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived endothelial cell growth factor (PD-ECGF), thrombospondin (TSP), angiogenin, pleiotrophin, and endostatin (ES) levels, as well as intratumor microvessel density (M
基金This work was supported by the Fundamental Research Funds for the Central Universities(WK2070000191,WK9110000037)the fellowship of China National Postdoctoral Program for Innovative Talents(BX20200325)the Natural Science Foundation of Anhui province(1808085QH244).
文摘The NLRP3 inflammasome is a cytosolic multiprotein complex composed of the innate immune receptor protein NLRP3,adapter protein ASC,and inflammatory protease caspase-1 that responds to microbial infection,endogenous danger signals,and environmental stimuli.The assembled NLRP3 inflammasome can activate the protease caspase‐1 to induce gasdermin D-dependent pyroptosis and facilitate the release of IL-1β and IL-18,which contribute to innate immune defense and homeostatic maintenance.However,aberrant activation of the NLRP3 inflammasome is associated with the pathogenesis of various inflammatory diseases,such as diabetes,cancer,and Alzheimer’s disease.Recent studies have revealed that NLRP3 inflammasome activation contributes to not only pyroptosis but also other types of cell death,including apoptosis,necroptosis,and ferroptosis.In addition,various effectors of cell death have been reported to regulate NLRP3 inflammasome activation,suggesting that cell death is closely related to NLRP3 inflammasome activation.In this review,we summarize the inextricable link between NLRP3 inflammasome activation and cell death and discuss potential therapeutics that target cell death effectors in NLRP3 inflammasome-associated diseases.
基金B.S.F.is supported by grants from the European Research Council(PLAT-IL-1,714175)B.S.F.and E.L.are further supported by grants from the Deutsche Forschungsgemeinschaft(DFG,German Research Foundation)(SFBTRR57)the DFG Germany’s Excellence Strategy-EXC 2151-390873048.
文摘Cell death is a fundamental physiological process in all living organisms.Its roles extend from embryonic development,organ maintenance,and aging to the coordination of immune responses and autoimmunity.In recent years,our understanding of the mechanisms orchestrating cellular death and its consequences on immunity and homeostasis has increased substantially.Different modalities of what has become known as‘programmed cell death’have been described,and some key players in these processes have been identified.We have learned more about the intricacies that fine tune the activity of common players and ultimately shape the different types of cell death.These studies have highlighted the complex mechanisms tipping the balance between different cell fates.Here,we summarize the latest discoveries in the three most well understood modalities of cell death,namely,apoptosis,necroptosis,and pyroptosis,highlighting common and unique pathways and their effect on the surrounding cells and the organism as a whole.
