Cancer development and its response to therapy are regulated by inflammation,which either promotes or suppresses tumor progression,potentially displaying opposing effects on therapeutic outcomes.Chronic inflammation f...Cancer development and its response to therapy are regulated by inflammation,which either promotes or suppresses tumor progression,potentially displaying opposing effects on therapeutic outcomes.Chronic inflammation facilitates tumor progression and treatment resistance,whereas induction of acute inflammatory reactions often stimulates the maturation of dendritic cells(DCs)and antigen presentation,leading to anti-tumor immune responses.In addition,multiple signaling pathways,such as nuclear factor kappa B(NF-kB),Janus kinase/signal transducers and activators of transcription(JAK-STAT),toll-like receptor(TLR)pathways,cGAS/STING,and mitogen-activated protein kinase(MAPK);inflammatory factors,including cytokines(e.g.,interleukin(IL),interferon(IFN),and tumor necrosis factor(TNF)-a),chemokines(e.g.,C-C motif chemokine ligands(CCLs)and C-X-C motif chemokine ligands(CXCLs)),growth factors(e.g.,vascular endothelial growth factor(VEGF),transforming growth factor(TGF)-P),and inflammasome;as well as inflammatory metabolites including prostaglandins,leukotrienes,thromboxane,and specialized proresolving mediators(SPM),have been identified as pivotal regulators of the initiation and resolution of inflammation.Nowadays,local irradiation,recombinant cytokines,neutralizing antibodies,small-molecule inhibitors,DC vaccines,oncolytic viruses,TLR agonists,and SPM have been developed to specifically modulate inflammation in cancer therapy,with some of these factors already undergoing clinical trials.Herein,we discuss the initiation and resolution of inflammation,the crosstalk between tumor development and inflammatory processes.We also highlight potential targets for harnessing inflammation in the treatment of cancer.展开更多
Recent studies have uncovered two signaling pathways that activate the host innate immunity against viral infection. One of the pathways utilizes members of the Toll-like receptor （TLR） family to detect viruses that...Recent studies have uncovered two signaling pathways that activate the host innate immunity against viral infection. One of the pathways utilizes members of the Toll-like receptor （TLR） family to detect viruses that enter the endosome through endocytosis. The TLR pathway induces interferon production through several signaling proteins that ultimately lead to the activation of the transcription factors NF-kB, IRF3 and IRFT. The other antiviral pathway uses the RNA helicase RIG-Ⅰ as the receptor for intracellular viral double-stranded RNA. RIG-Ⅰ activates NF-kB and IRFs through the recently identified adaptor protein MAVS, a CARD domain containing protein that resides in the mitochondrial membrane. MAVS is essential for antiviral innate immunity, but it also serves as a target of Hepatitis C virus （HCV）, which employs a viral protease to cleave MAVS off the mitochondria, thereby allowing HCV to escape the host immune system.展开更多
Hepatitis B virus （HBV） infection is still the most common cause of hepatocellular carcinoma and liver drrhosis world wide. Recently, however, there has been quite dramatic improvement in the understanding of HBV as...Hepatitis B virus （HBV） infection is still the most common cause of hepatocellular carcinoma and liver drrhosis world wide. Recently, however, there has been quite dramatic improvement in the understanding of HBV assodated liver disease and its treatment. It has become dear that high viral replication is a major risk factor for the development of both cirrhosis and hepatocellular carcinoma. Early studies have shown lamivudine lowers the risk of HBV associated complications. There are currently three nucleos（t）ides licensed, in addition to interferon, and there are more drugs coming to the market soon. Interferon or its pegylated counterpart are still the only options for treatment with defined end points, while nudeos（t）ides therapy is used mostly for long term treatment. Combination therapies have not been shown to be superior to monotherapy in naive patients, however, the outcome depends on how the end point is defined. Interferon plus lamivudine achieves a higher viral suppression than either treatment alone, even though Hbe-seroconversion was not different after a one year treatment. HBV-genotypes emerge as relevant factors, with genotypes ＂A＂ and ＂B＂ responding relatively well to interferon, achieving up to 20% HBsAg clearance in the case of genotype ＂A＂. In addition to having a defined treatment duration, interferon has the advantage of lack- ing resistance selection, which is a major drawback for lamivudine and the other nucleos（t）ides. The emergence of resistance against adefovir and entecavir is some- what slower in na＇fve compared to lamivudine resistant patients. Adefovir has a low resistance profile with 3%, 9%, 18%, and 28% after 2, 3, 4, and 5 years, respectively, while entecavir has rarely produced resistance in naive patients for up to 3 years.展开更多
Chronic hepatitis B(CHB)virus infection is a global public health problem,affecting more than 400 million people worldwide.The clinical spectrum is wide,ranging from a subclinical inactive carrier state,to progressive...Chronic hepatitis B(CHB)virus infection is a global public health problem,affecting more than 400 million people worldwide.The clinical spectrum is wide,ranging from a subclinical inactive carrier state,to progressive chronic hepatitis,cirrhosis,decompensation,and hepatocellular carcinoma.However,complications of hepatitis B virus(HBV)-related chronic liver disease may be reduced by viral suppression.Current international guidelines recommend first-line treatment of CHB infection with pegylated interferon,entecavir,or tenofovir,but the optimal treatment for an individualpatient is controversial.The indications for treatment are contentious,and increasing evidence suggests that HBV genotyping,as well as serial on-treatment measurements of hepatitis B surface antigen and HBV DNA kinetics should be used to predict antiviral treatment response.The likelihood of achieving a sustained virological response is also increased by extending treatment duration,and using combination therapy.Hence the paradigm for treatment of CHB is constantly evolving.This article summarizes the different indications for treatment,and systematically reviews the evidence for the efficacy of various antiviral agents.It further discusses the shortcomings of current guidelines,use of rescue therapy in drug-resistant strains of HBV,and highlights the promising clinical trials for emerging therapies in the pipeline.This concise overview presents an updated practical approach to guide the clinical management of CHB.展开更多
基金This work was supported by the Major International(Regional)Joint Research Program of the National Natural Science Foundation of China(No.81920108027)Chongqing Outstanding Youth Science Foundation,Chongqing Talent Innovation Leader Project,and Funding for Chongqing University Innovation Research Group.
文摘Cancer development and its response to therapy are regulated by inflammation,which either promotes or suppresses tumor progression,potentially displaying opposing effects on therapeutic outcomes.Chronic inflammation facilitates tumor progression and treatment resistance,whereas induction of acute inflammatory reactions often stimulates the maturation of dendritic cells(DCs)and antigen presentation,leading to anti-tumor immune responses.In addition,multiple signaling pathways,such as nuclear factor kappa B(NF-kB),Janus kinase/signal transducers and activators of transcription(JAK-STAT),toll-like receptor(TLR)pathways,cGAS/STING,and mitogen-activated protein kinase(MAPK);inflammatory factors,including cytokines(e.g.,interleukin(IL),interferon(IFN),and tumor necrosis factor(TNF)-a),chemokines(e.g.,C-C motif chemokine ligands(CCLs)and C-X-C motif chemokine ligands(CXCLs)),growth factors(e.g.,vascular endothelial growth factor(VEGF),transforming growth factor(TGF)-P),and inflammasome;as well as inflammatory metabolites including prostaglandins,leukotrienes,thromboxane,and specialized proresolving mediators(SPM),have been identified as pivotal regulators of the initiation and resolution of inflammation.Nowadays,local irradiation,recombinant cytokines,neutralizing antibodies,small-molecule inhibitors,DC vaccines,oncolytic viruses,TLR agonists,and SPM have been developed to specifically modulate inflammation in cancer therapy,with some of these factors already undergoing clinical trials.Herein,we discuss the initiation and resolution of inflammation,the crosstalk between tumor development and inflammatory processes.We also highlight potential targets for harnessing inflammation in the treatment of cancer.
文摘Recent studies have uncovered two signaling pathways that activate the host innate immunity against viral infection. One of the pathways utilizes members of the Toll-like receptor （TLR） family to detect viruses that enter the endosome through endocytosis. The TLR pathway induces interferon production through several signaling proteins that ultimately lead to the activation of the transcription factors NF-kB, IRF3 and IRFT. The other antiviral pathway uses the RNA helicase RIG-Ⅰ as the receptor for intracellular viral double-stranded RNA. RIG-Ⅰ activates NF-kB and IRFs through the recently identified adaptor protein MAVS, a CARD domain containing protein that resides in the mitochondrial membrane. MAVS is essential for antiviral innate immunity, but it also serves as a target of Hepatitis C virus （HCV）, which employs a viral protease to cleave MAVS off the mitochondria, thereby allowing HCV to escape the host immune system.
基金Supported by the German BMBF and Network for competence in viral hepatitis
文摘Hepatitis B virus （HBV） infection is still the most common cause of hepatocellular carcinoma and liver drrhosis world wide. Recently, however, there has been quite dramatic improvement in the understanding of HBV assodated liver disease and its treatment. It has become dear that high viral replication is a major risk factor for the development of both cirrhosis and hepatocellular carcinoma. Early studies have shown lamivudine lowers the risk of HBV associated complications. There are currently three nucleos（t）ides licensed, in addition to interferon, and there are more drugs coming to the market soon. Interferon or its pegylated counterpart are still the only options for treatment with defined end points, while nudeos（t）ides therapy is used mostly for long term treatment. Combination therapies have not been shown to be superior to monotherapy in naive patients, however, the outcome depends on how the end point is defined. Interferon plus lamivudine achieves a higher viral suppression than either treatment alone, even though Hbe-seroconversion was not different after a one year treatment. HBV-genotypes emerge as relevant factors, with genotypes ＂A＂ and ＂B＂ responding relatively well to interferon, achieving up to 20% HBsAg clearance in the case of genotype ＂A＂. In addition to having a defined treatment duration, interferon has the advantage of lack- ing resistance selection, which is a major drawback for lamivudine and the other nucleos（t）ides. The emergence of resistance against adefovir and entecavir is some- what slower in na＇fve compared to lamivudine resistant patients. Adefovir has a low resistance profile with 3%, 9%, 18%, and 28% after 2, 3, 4, and 5 years, respectively, while entecavir has rarely produced resistance in naive patients for up to 3 years.
基金Supported by Collaborative Research Fund(CUHK3/CRF/12RHKU3/CRF11R)of the Research Grant Council Hong Kong+2 种基金National Basic Research Program of China,973 Program,No.2013CB531401CUHK Focused Investments Scheme B to HY LanTheme-based Research Scheme of the Hong Kong Re-search Grants Council,No.T12-403-11
文摘Chronic hepatitis B(CHB)virus infection is a global public health problem,affecting more than 400 million people worldwide.The clinical spectrum is wide,ranging from a subclinical inactive carrier state,to progressive chronic hepatitis,cirrhosis,decompensation,and hepatocellular carcinoma.However,complications of hepatitis B virus(HBV)-related chronic liver disease may be reduced by viral suppression.Current international guidelines recommend first-line treatment of CHB infection with pegylated interferon,entecavir,or tenofovir,but the optimal treatment for an individualpatient is controversial.The indications for treatment are contentious,and increasing evidence suggests that HBV genotyping,as well as serial on-treatment measurements of hepatitis B surface antigen and HBV DNA kinetics should be used to predict antiviral treatment response.The likelihood of achieving a sustained virological response is also increased by extending treatment duration,and using combination therapy.Hence the paradigm for treatment of CHB is constantly evolving.This article summarizes the different indications for treatment,and systematically reviews the evidence for the efficacy of various antiviral agents.It further discusses the shortcomings of current guidelines,use of rescue therapy in drug-resistant strains of HBV,and highlights the promising clinical trials for emerging therapies in the pipeline.This concise overview presents an updated practical approach to guide the clinical management of CHB.
