Autoimmune cholangitis would be the appropriate name to define the immune-mediated bile duct injury following the breakdown of tolerance to mitochondrial proteins and the appearance of serum autoantibodies and autorea...Autoimmune cholangitis would be the appropriate name to define the immune-mediated bile duct injury following the breakdown of tolerance to mitochondrial proteins and the appearance of serum autoantibodies and autoreactive T cells.Nevertheless,the conditionis universally named primary biliary cirrhosis(PBC).The disease etiology and pathogenesis remain largely unknown despite the proposed lines of evidence.One twin study and numerous epidemiology reportssuggest that both a susceptible genetic background and environmental factors determine disease onsetwhile a recent genome-wide association study proposed highly significant associations with several commongenetic polymorphisms in subgroups of patients.Specific infectious agents and chemicals may contribute to the disease onset and perpetuation in a geneticallysusceptible host,possibly through molecular mimicry.Importantly,several murine models have been proposed and include strains in which PBC is genetically determined or induced by immunization with chemicals and bacteria.From a pathogenetic standpoint,new exciting data have demonstrated the unique apoptotic features of bile duct cells that allow the mitochondrial autoantigens to be taken up in their intact form within apoptotic blebs.We are convinced that the application of the most recent molecular techniques will soon pro-vide developments in PBC etiology and pathogenesis with likely implications in diagnostics and therapeutics.展开更多
Colorectal cancer(CRC)is a significant health problem,with around 1 million new cases and 500000 deaths every year worldwide.Over the last two decades,the use of novel therapies and more complex treatment strategies h...Colorectal cancer(CRC)is a significant health problem,with around 1 million new cases and 500000 deaths every year worldwide.Over the last two decades,the use of novel therapies and more complex treatment strategies have contributed to progressively increase the median survival of patients with unresectable advanced CRC up to approximately 30 mo.The availability of additional therapeutic options,however,has created new challenges and generated more complicated treatment algorithms.Moreover,several clinically important points are still in debate in first-line,such as the optimal treatment intensity,the most appropriate maintenance strategy,the preferred biologic to be used upfront in patients with KRAS wild-type CRC,and the need for more detailed information on tumor biology.In this moving landscape,this review analyses why the firstline treatment decision is crucial and how the choicemay impact on further treatment lines.In addition,it focuses on results of major phaseⅢrandomized trials.展开更多
文摘Autoimmune cholangitis would be the appropriate name to define the immune-mediated bile duct injury following the breakdown of tolerance to mitochondrial proteins and the appearance of serum autoantibodies and autoreactive T cells.Nevertheless,the conditionis universally named primary biliary cirrhosis(PBC).The disease etiology and pathogenesis remain largely unknown despite the proposed lines of evidence.One twin study and numerous epidemiology reportssuggest that both a susceptible genetic background and environmental factors determine disease onsetwhile a recent genome-wide association study proposed highly significant associations with several commongenetic polymorphisms in subgroups of patients.Specific infectious agents and chemicals may contribute to the disease onset and perpetuation in a geneticallysusceptible host,possibly through molecular mimicry.Importantly,several murine models have been proposed and include strains in which PBC is genetically determined or induced by immunization with chemicals and bacteria.From a pathogenetic standpoint,new exciting data have demonstrated the unique apoptotic features of bile duct cells that allow the mitochondrial autoantigens to be taken up in their intact form within apoptotic blebs.We are convinced that the application of the most recent molecular techniques will soon pro-vide developments in PBC etiology and pathogenesis with likely implications in diagnostics and therapeutics.
文摘Colorectal cancer(CRC)is a significant health problem,with around 1 million new cases and 500000 deaths every year worldwide.Over the last two decades,the use of novel therapies and more complex treatment strategies have contributed to progressively increase the median survival of patients with unresectable advanced CRC up to approximately 30 mo.The availability of additional therapeutic options,however,has created new challenges and generated more complicated treatment algorithms.Moreover,several clinically important points are still in debate in first-line,such as the optimal treatment intensity,the most appropriate maintenance strategy,the preferred biologic to be used upfront in patients with KRAS wild-type CRC,and the need for more detailed information on tumor biology.In this moving landscape,this review analyses why the firstline treatment decision is crucial and how the choicemay impact on further treatment lines.In addition,it focuses on results of major phaseⅢrandomized trials.
