Tumor-derived extracellular vesicles(EVs)have emerged as promising targets for liquid biopsy,enabling noninvasive mRNA profling to support cancer detection,staging,and treatment monitoring.This Review highlights the d...Tumor-derived extracellular vesicles(EVs)have emerged as promising targets for liquid biopsy,enabling noninvasive mRNA profling to support cancer detection,staging,and treatment monitoring.This Review highlights the development and clinica translation of EV Digital Scoring Assays,an innovative class of two-step liquid biopsy platforms integrating click chemistry-mediated tumor EV enrichment(via EV Click Beads or EV Click Chips)with reverse transcription digital PCR(RT-dPCR)for absolute quantification of tumor mRNA.These assays have demonstrated clinical utility across multiple solid tumors:identifying oncogenic alterations in pancreatic ductal adenocarcinoma and Ewing sarcoma,detecting early stage hepatocellular carcinoma in at-risk cirrhotic patients,differentiating localized from metastatic prostate cancer,and monitoring treatment response in hepatocellular carcinoma.We also examine emerging technologies and parallel efforts from other groups,including microfluidic isolation platforms PCR-free digital detection,and machine learning-based analytics.Together,these studies showcase how“enrich-then-count”strategies can overcome challenges in tumor EV specificity and transcript quantification,offering scalable solutions for precision oncology.The EV Digital Scoring Assay provides a versatile and modular platform,potentially enabling broad adoption across diverse tumor types and clinical contexts for real-time noninvasive cancer management.展开更多
Background and Aims:Hepatitis C virus (HCV) cirrhosis is the leading indication for liver transplantation in the United States and recurrent HCV following liver transplantation is a major cause of allograft loss and m...Background and Aims:Hepatitis C virus (HCV) cirrhosis is the leading indication for liver transplantation in the United States and recurrent HCV following liver transplantation is a major cause of allograft loss and mortality.Liver biopsies are commonly used to identify recurrent HCV and determine the need for antiviral therapy.The introduction of directacting antiviral agents (DAAs) has changed the management of recurrent HCV infection.This study aimed to describe the role of liver biopsies in liver transplant recipients with HCV after the introduction of DAAs.Methods:A retrospective analysis was performed looking at the rate of liver biopsies post-liver transplantation for HCV.The analysis included 475 adult liver transplants for hepatitis C performed at the University of California,Los Angeles from January 1,2006 to October 1,2015.Patients were divided into two eras,pre-and post-introduction of DAAs on December 1,2013.Results:In the era before the introduction of DAAs,the percentage of patients biopsied was significantly higher compared to the era after the introduction of DAAs (56.1% vs.26.9%,p < 0.001).Conclusion:The introduction of DAAs has changed the management of liver biopsy following liver transplantation and the management of recurrent HCV.Given that DAAs are well tolerated and have high efficacy,liver biopsies are no longer routinely used to justify the use antiviral therapy following liver transplantation.展开更多
基金supported by National Institutes of Health(R01CA298883,R01CA277530,R01CA255727,R01CA253651,R01CA253651-04S1,R01CA246304,U01EB026421,K08CA259534,and R44CA288163)Hyundai Hope on Wheels Scholar Grant(20233377).
文摘Tumor-derived extracellular vesicles(EVs)have emerged as promising targets for liquid biopsy,enabling noninvasive mRNA profling to support cancer detection,staging,and treatment monitoring.This Review highlights the development and clinica translation of EV Digital Scoring Assays,an innovative class of two-step liquid biopsy platforms integrating click chemistry-mediated tumor EV enrichment(via EV Click Beads or EV Click Chips)with reverse transcription digital PCR(RT-dPCR)for absolute quantification of tumor mRNA.These assays have demonstrated clinical utility across multiple solid tumors:identifying oncogenic alterations in pancreatic ductal adenocarcinoma and Ewing sarcoma,detecting early stage hepatocellular carcinoma in at-risk cirrhotic patients,differentiating localized from metastatic prostate cancer,and monitoring treatment response in hepatocellular carcinoma.We also examine emerging technologies and parallel efforts from other groups,including microfluidic isolation platforms PCR-free digital detection,and machine learning-based analytics.Together,these studies showcase how“enrich-then-count”strategies can overcome challenges in tumor EV specificity and transcript quantification,offering scalable solutions for precision oncology.The EV Digital Scoring Assay provides a versatile and modular platform,potentially enabling broad adoption across diverse tumor types and clinical contexts for real-time noninvasive cancer management.
文摘Background and Aims:Hepatitis C virus (HCV) cirrhosis is the leading indication for liver transplantation in the United States and recurrent HCV following liver transplantation is a major cause of allograft loss and mortality.Liver biopsies are commonly used to identify recurrent HCV and determine the need for antiviral therapy.The introduction of directacting antiviral agents (DAAs) has changed the management of recurrent HCV infection.This study aimed to describe the role of liver biopsies in liver transplant recipients with HCV after the introduction of DAAs.Methods:A retrospective analysis was performed looking at the rate of liver biopsies post-liver transplantation for HCV.The analysis included 475 adult liver transplants for hepatitis C performed at the University of California,Los Angeles from January 1,2006 to October 1,2015.Patients were divided into two eras,pre-and post-introduction of DAAs on December 1,2013.Results:In the era before the introduction of DAAs,the percentage of patients biopsied was significantly higher compared to the era after the introduction of DAAs (56.1% vs.26.9%,p < 0.001).Conclusion:The introduction of DAAs has changed the management of liver biopsy following liver transplantation and the management of recurrent HCV.Given that DAAs are well tolerated and have high efficacy,liver biopsies are no longer routinely used to justify the use antiviral therapy following liver transplantation.
