Hepatocellular carcinoma(HCC)is the most common primary cancer of the liver and has an overall five-year survival rate of less than twenty percent.For patients with unresectable disease,evolving liver-directed locoreg...Hepatocellular carcinoma(HCC)is the most common primary cancer of the liver and has an overall five-year survival rate of less than twenty percent.For patients with unresectable disease,evolving liver-directed locoregional therapies provide efficacious treatment across the spectrum of disease stages and via a variety of catheter-directed and percutaneous techniques.Goals of locoregional therapies in HCC may include curative intent in early-stage disease,bridging or downstaging to surgical resection or transplantation for early or intermediate-stage disease,and local disease control and palliation in advanced-stage disease.This review explores the outcomes of chemoembolization,bland embolization,radioembolization,and percutaneous ablative therapies.Attention is also given to prognostic factors related to each of the respective techniques,as well as future directions of locoregional therapies for HCC.展开更多
SARS-CoV-2,the coronavirus that causes the disease COVID-19,has claimed millions of lives over the past 2 years.This demands rapid development of effective therapeutic agents that target various phases of the viral re...SARS-CoV-2,the coronavirus that causes the disease COVID-19,has claimed millions of lives over the past 2 years.This demands rapid development of effective therapeutic agents that target various phases of the viral replication cycle.The interaction between host transmembrane serine protease 2(TMPRSS2)and viral SPIKE protein is an important initial step in SARS-CoV-2 infection,offering an opportunity for therapeutic development of viral entry inhibitors.Here,we report the development of a time-resolved fluorescence/Förster resonance energy transfer(TR-FRET)assay for monitoring the TMPRSS2–SPIKE interaction in lysate from cells co-expressing these proteins.The assay was configured in a 384-well-plate format for high-throughput screening with robust assay performance.To enable large-scale compound screening,we further miniaturized the assay into 1536-well ultrahigh-throughput screening(uHTS)format.A pilot screen demonstrated the utilization of the assay for uHTS.Our optimized TR-FRET uHTS assay provides an enabling platform for expanded screening campaigns to discover new classes of small-molecule inhibitors that target the SPIKE and TMPRSS2 protein–protein interaction.展开更多
文摘Hepatocellular carcinoma(HCC)is the most common primary cancer of the liver and has an overall five-year survival rate of less than twenty percent.For patients with unresectable disease,evolving liver-directed locoregional therapies provide efficacious treatment across the spectrum of disease stages and via a variety of catheter-directed and percutaneous techniques.Goals of locoregional therapies in HCC may include curative intent in early-stage disease,bridging or downstaging to surgical resection or transplantation for early or intermediate-stage disease,and local disease control and palliation in advanced-stage disease.This review explores the outcomes of chemoembolization,bland embolization,radioembolization,and percutaneous ablative therapies.Attention is also given to prognostic factors related to each of the respective techniques,as well as future directions of locoregional therapies for HCC.
基金supported in part by the Emory School of Medicine COVID Catalyst-I3 award(H.F.and S.G.S.)the NCI Emory Lung Cancer SPORE(P50CA217691)Career Enhancement Program(A.A.I.)+1 种基金Emory Initiative on Biological Discovery through Chemical Innovation(A.A.I.)R01AI167356(S.G.S.).
文摘SARS-CoV-2,the coronavirus that causes the disease COVID-19,has claimed millions of lives over the past 2 years.This demands rapid development of effective therapeutic agents that target various phases of the viral replication cycle.The interaction between host transmembrane serine protease 2(TMPRSS2)and viral SPIKE protein is an important initial step in SARS-CoV-2 infection,offering an opportunity for therapeutic development of viral entry inhibitors.Here,we report the development of a time-resolved fluorescence/Förster resonance energy transfer(TR-FRET)assay for monitoring the TMPRSS2–SPIKE interaction in lysate from cells co-expressing these proteins.The assay was configured in a 384-well-plate format for high-throughput screening with robust assay performance.To enable large-scale compound screening,we further miniaturized the assay into 1536-well ultrahigh-throughput screening(uHTS)format.A pilot screen demonstrated the utilization of the assay for uHTS.Our optimized TR-FRET uHTS assay provides an enabling platform for expanded screening campaigns to discover new classes of small-molecule inhibitors that target the SPIKE and TMPRSS2 protein–protein interaction.
