Hepatitis C virus(HCV) infects more than 170 million people worldwide,and thereby becomes a series global health challenge.Chronic infection with HCV is considered one of the major causes of end-stage liver disease in...Hepatitis C virus(HCV) infects more than 170 million people worldwide,and thereby becomes a series global health challenge.Chronic infection with HCV is considered one of the major causes of end-stage liver disease including cirrhosis and hepatocellular carcinoma.Although the multiple functions of the HCV proteins and their impacts on the modulation of the intracellular signaling transduction processes,the drive of carcinogenesis during the infection with HCV,is thought to result from the interactions of viral proteins with host cell proteins.Thus,the induction of mutator phenotype,in liver,by the expression of HCV proteins provides a key mechanism for the development of HCV-associated hepatocellular carcinoma(HCC).HCC is considered one of the most common malignancies worldwide with increasing incidence during the past decades.In many countries,the trend of HCC is attributed to several liver diseases including HCV infection.However,the development of HCC is very complicated and results mainly from the imbalance between tumor suppressor genes and oncogenes,as well as from the alteration of cellular factors leading to a genomic instability.Besides the poor prognosis of HCC patients,this type of tumor is quite resistance to the available therapies.Thus,understanding the molecular mechanisms,which are implicated in the development of HCC during the course of HCV infection,may help to design a general therapeutic protocol for the treatment and/or the prevention of this malignancy.This review summarizes the current knowledge of the molecular mechanisms,which are involved in the development of HCV-associated HCC and the possible therapeutic strategies.展开更多
Angiogenesis is an essential process for organ growth and repair. Thus, an imbalance in this process can lead to several diseases including malignancy. Angiogenesis is a critical step in vascular remodeling, tissue da...Angiogenesis is an essential process for organ growth and repair. Thus, an imbalance in this process can lead to several diseases including malignancy. Angiogenesis is a critical step in vascular remodeling, tissue damage and wound healing besides being required for invasive tumor growth and metastasis. Because angiogenesis sets an important point in the control of tumor progression, its inhibition is considered a valuable therapeutic approach for tumor treatment. Chronic liver disease including hepatitis C virus(HCV) infection is one of the main cause for the development of hepatic angiogenesis and thereby plays a critical role in the modulation of hepatic angiogenesis that finally leads to hepatocellular carcinoma progression and invasion. Thus, understanding of the molecular mechanisms of HCV-mediated hepatic angiogenesis will help design a therapeutic protocol for the intervention of HCV-mediated angiogenesis and subsequently its outcome. In this review, we will focus on the molecular mechanisms of HCV-mediated hepatic angiogenesis and the related signaling pathways that can be target for current and under development therapeutic approaches.展开更多
Hepatitis C virus(HCV) is a significant health problem facing the world. This virus infects more than 170 million people worldwide and is considered the major cause of both acute and chronic hepatitis. Persons become ...Hepatitis C virus(HCV) is a significant health problem facing the world. This virus infects more than 170 million people worldwide and is considered the major cause of both acute and chronic hepatitis. Persons become infected mainly through parenteral exposure to infected material by blood transfusions or injections with nonsterile needles. Although the sexual behavior is considered as a high risk factor for HCV infection, the transmission of HCV infection through sexual means, is less frequently. Currently, the available treatment for patients with chronic HCV infection is interferon basedtherapies alone or in combination with ribavirin and protease inhibitors. Although a sustained virological response of patients to the applied therapy, a great portion of patients did not show any response. HCV infection is mostly associated with progressive liver diseases including fibrosis, cirrhosis and hepatocellular carcinoma. Although the focus of many patients and clinicians is sometimes limited to that problem, the natural history of HCV infection(HCV) is also associated with the development of several extrahepatic manifestations including dermatologic, rheumatologic, neurologic, and nephrologic complications, diabetes, arterial hypertension, autoantibodies and cryglobulins. Despite the notion that HCV-mediated extrahepatic manifestations are credible, the mechanism of their modulation is not fully described in detail. Therefore, the understanding of the molecular mechanisms of HCV-induced alteration of intracellular signal transduction pathways, during the course of HCV infection, may offer novel therapeutic targets for HCV-associated both hepatic and extrahepatic manifestations. This review will elaborate the etiopathogenesis of HCV-host interactions and summarize the current knowledge of HCV-associated diseases and their possible therapeutic strategies.展开更多
文摘Hepatitis C virus(HCV) infects more than 170 million people worldwide,and thereby becomes a series global health challenge.Chronic infection with HCV is considered one of the major causes of end-stage liver disease including cirrhosis and hepatocellular carcinoma.Although the multiple functions of the HCV proteins and their impacts on the modulation of the intracellular signaling transduction processes,the drive of carcinogenesis during the infection with HCV,is thought to result from the interactions of viral proteins with host cell proteins.Thus,the induction of mutator phenotype,in liver,by the expression of HCV proteins provides a key mechanism for the development of HCV-associated hepatocellular carcinoma(HCC).HCC is considered one of the most common malignancies worldwide with increasing incidence during the past decades.In many countries,the trend of HCC is attributed to several liver diseases including HCV infection.However,the development of HCC is very complicated and results mainly from the imbalance between tumor suppressor genes and oncogenes,as well as from the alteration of cellular factors leading to a genomic instability.Besides the poor prognosis of HCC patients,this type of tumor is quite resistance to the available therapies.Thus,understanding the molecular mechanisms,which are implicated in the development of HCC during the course of HCV infection,may help to design a general therapeutic protocol for the treatment and/or the prevention of this malignancy.This review summarizes the current knowledge of the molecular mechanisms,which are involved in the development of HCV-associated HCC and the possible therapeutic strategies.
基金Supported by Grant from German Research Foundation,No.HA 5081/3-1German cancer foundation,No.10-2202-Ha1L'Alsace contre le Cancer,France(to Hassan M)
文摘Angiogenesis is an essential process for organ growth and repair. Thus, an imbalance in this process can lead to several diseases including malignancy. Angiogenesis is a critical step in vascular remodeling, tissue damage and wound healing besides being required for invasive tumor growth and metastasis. Because angiogenesis sets an important point in the control of tumor progression, its inhibition is considered a valuable therapeutic approach for tumor treatment. Chronic liver disease including hepatitis C virus(HCV) infection is one of the main cause for the development of hepatic angiogenesis and thereby plays a critical role in the modulation of hepatic angiogenesis that finally leads to hepatocellular carcinoma progression and invasion. Thus, understanding of the molecular mechanisms of HCV-mediated hepatic angiogenesis will help design a therapeutic protocol for the intervention of HCV-mediated angiogenesis and subsequently its outcome. In this review, we will focus on the molecular mechanisms of HCV-mediated hepatic angiogenesis and the related signaling pathways that can be target for current and under development therapeutic approaches.
文摘Hepatitis C virus(HCV) is a significant health problem facing the world. This virus infects more than 170 million people worldwide and is considered the major cause of both acute and chronic hepatitis. Persons become infected mainly through parenteral exposure to infected material by blood transfusions or injections with nonsterile needles. Although the sexual behavior is considered as a high risk factor for HCV infection, the transmission of HCV infection through sexual means, is less frequently. Currently, the available treatment for patients with chronic HCV infection is interferon basedtherapies alone or in combination with ribavirin and protease inhibitors. Although a sustained virological response of patients to the applied therapy, a great portion of patients did not show any response. HCV infection is mostly associated with progressive liver diseases including fibrosis, cirrhosis and hepatocellular carcinoma. Although the focus of many patients and clinicians is sometimes limited to that problem, the natural history of HCV infection(HCV) is also associated with the development of several extrahepatic manifestations including dermatologic, rheumatologic, neurologic, and nephrologic complications, diabetes, arterial hypertension, autoantibodies and cryglobulins. Despite the notion that HCV-mediated extrahepatic manifestations are credible, the mechanism of their modulation is not fully described in detail. Therefore, the understanding of the molecular mechanisms of HCV-induced alteration of intracellular signal transduction pathways, during the course of HCV infection, may offer novel therapeutic targets for HCV-associated both hepatic and extrahepatic manifestations. This review will elaborate the etiopathogenesis of HCV-host interactions and summarize the current knowledge of HCV-associated diseases and their possible therapeutic strategies.
