ABSTRACT
Purpose@#Cancer stem cells (CSCs) are naturally resistant to chemotherapy, explaining why tumorrelapse frequently occurs after initial regression upon administration of chemotherapeuticagents in most cases. A CSC population characterized by CD13 expression has been identifiedin hepatocellular carcinoma (HCC). In the current study, we aimed to clarify the molecularmechanism by which it escapes conventional therapies. @*Materials and Methods@#Here, we used flow cytometry to examine the percentage of CD13+ CSCs in HepG2 andHuH7 cells after chemotherapy. Using in vitro isotope labeling technique, we comparedmetabolic pathways between CD13+ and CD13– subpopulations. Using co-immunoprecipitationand western blotting, we determined the target expressions in protein levels underdifferent conditions. We also performed immunohistochemistry to detect the target proteinsunder different conditions. Animal models were constructed to verify the potential role oftyrosine metabolism in post-chemotherapeutic relapse in vivo. @*Results@#We observed that quiescent CD13+ CSCs are enriched after chemotherapy in HCCs, andserve as a reservoir for recurrence. Mechanistically, CD13+ CSCs were dependent on aerobicmetabolism of tyrosine rather than glucose as energy source. Tyrosine metabolism alsogenerated nuclear acetyl-CoA to acetylate and stabilize Foxd3, thereby allowing CD13+ CSCscells to sustain quiescence and resistance to chemotherapeutic agents. @*Conclusion@#These findings encourage further exploration of eliminating CD13+ cells by targeting specificmetabolic pathways to prevent recurrence in HCCs.
ABSTRACT
Objective To explore the value of endothelial dysfunction assessment in predicating major adverse cardiac and cerebrovascular events (MACCE) in peritoneal dialysis (PD) patients.Methods A prospective cohort study included 136 end stage renal disease (ESRD) patients from Jan 1,2009 to Dec 31,2011 was conducted.Endothelial function was assessed by flowmediated dilation (FMD) of brachial artery.Kaplan-Meier method was used to estimate survival rate.The survival difference between the two groups was compared by the log-rank test.Multivariate Cox proportional hazards regression was used to determine the independent risk factors of MACCE.Results In the follow-up period,18 patients in low FMD (FMD≤2.7％) group occurred MACCE,and 13 patients in high FMD (FMD ＞ 2.7％) group occurred MACCE.Compared with high FMD group,MACCE-free survival rate in the low FMD group had a significantly decreased (x2=4.190,P=0.041).Multivariate Cox proportional hazards regression analysis showed that higher level of total cholesterol,lower FMD,longer PD time and higher levels of hs-CRP were all independent predictors of MACCE.Conclusion Reduced brachial artery FMD is an independent risk factor of MACCE,and the application of FMD contributes to the risk stratification of cardiac and cerebrovascular disease in PD patients.