Epigenetic alterations have been identified as a major characteristic in human cancers.Advances in the field of epigenetics have contributed significantly in refining our knowledge of molecular mechanisms underlying m...Epigenetic alterations have been identified as a major characteristic in human cancers.Advances in the field of epigenetics have contributed significantly in refining our knowledge of molecular mechanisms underlying malignant transformation.DNA methylation and microRNA expression are epigenetic mechanisms that are widely altered in human cancers including hepatocellular carcinoma(HCC),the third leading cause of cancer related mortality worldwide.Both DNA methylation and microRNA expression patterns are regulated in developmental stage specific-,cell type specific-and tissue-specific manner.The aberrations are inferred in the maintenance of cancer stem cells and in clonal cell evolution during carcinogenesis.The availability of genome-wide technologies for DNA methylation and microRNA profiling has revolutionized the field of epigenetics and led to the discovery of a number of epigenetically silenced microRNAs in cancerous cells and primary tissues.Dysregulation of these microRNAs affects several key signalling pathways in hepatocarcinogenesis suggesting that modulation of DNA methylation and/or microRNA expression can serve as new therapeutic targets for HCC.Accumulative evidence shows that aberrant DNA methylation of certain microRNA genes is an event specifically found in HCC which correlates with unfavorable outcomes.Therefore,it can potentially serve as a biomarker for detection as well as for prognosis,monitoring and predicting therapeutic responses in HCC.展开更多
AIM:To investigate the usefulness of branched-chain amino acids(BCAA)before transarterial chemoembolization(TACE)or radiofrequency ablation(RFA).METHODS:We investigated the usefulness of preintervention with BCAAs by ...AIM:To investigate the usefulness of branched-chain amino acids(BCAA)before transarterial chemoembolization(TACE)or radiofrequency ablation(RFA).METHODS:We investigated the usefulness of preintervention with BCAAs by comparing patients treated with BCAAs at 12.45 g/d orally for at least 2 wk before TACE or RFA and those not receiving such pretreatment.A total of 270 patients with hepatocellular carcinoma complicated by cirrhosis were included in the study.Mean changes from baseline(Δ)in serum albumin(Alb),C-reactive protein(CRP),and transaminase levels,as well as peak body temperature were also determined and compared at days 2,5,and 10 after the start of TACE or RFA.RESULTS:In patients who underwent TACE or RFA,BCAA pre-intervention significantly suppressed the development of post-intervention hypoalbuminemia and reduced inflammatory reactions during the subsequent clinical course.After TACE,theΔAlb peaked on day 2,remained constantly lower in BCAA-treated patients,compared to the control group,and was-0.13±0.42g/dL in BCAA-treated patients and-0.33±0.51 g/dL in untreated patients on day 10.TheΔCRP was also significantly lower in BCAA-treated patients on days2,5 and 10 after TACE.Like the trends noted after TACE,a similar tendency was noted as to theΔAlb andΔCRP after RFA.The changes in serum Alb level were inversely correlated with CRP changes;therefore,a possible involvement of the anti-inflammatory effect of BCAAs was inferred as a factor contributory to the suppression of decrease in serum Alb level.CONCLUSION:Pre-intervention with BCAAs may hasten the recovery of serum Alb level and mitigate postoperative complications in patients undergoing TACE or RFA.展开更多
基金Supported by Grant from the German Research Council(DFG),SFB-TRR77"Liver cancer"(Project B1)
文摘Epigenetic alterations have been identified as a major characteristic in human cancers.Advances in the field of epigenetics have contributed significantly in refining our knowledge of molecular mechanisms underlying malignant transformation.DNA methylation and microRNA expression are epigenetic mechanisms that are widely altered in human cancers including hepatocellular carcinoma(HCC),the third leading cause of cancer related mortality worldwide.Both DNA methylation and microRNA expression patterns are regulated in developmental stage specific-,cell type specific-and tissue-specific manner.The aberrations are inferred in the maintenance of cancer stem cells and in clonal cell evolution during carcinogenesis.The availability of genome-wide technologies for DNA methylation and microRNA profiling has revolutionized the field of epigenetics and led to the discovery of a number of epigenetically silenced microRNAs in cancerous cells and primary tissues.Dysregulation of these microRNAs affects several key signalling pathways in hepatocarcinogenesis suggesting that modulation of DNA methylation and/or microRNA expression can serve as new therapeutic targets for HCC.Accumulative evidence shows that aberrant DNA methylation of certain microRNA genes is an event specifically found in HCC which correlates with unfavorable outcomes.Therefore,it can potentially serve as a biomarker for detection as well as for prognosis,monitoring and predicting therapeutic responses in HCC.
文摘AIM:To investigate the usefulness of branched-chain amino acids(BCAA)before transarterial chemoembolization(TACE)or radiofrequency ablation(RFA).METHODS:We investigated the usefulness of preintervention with BCAAs by comparing patients treated with BCAAs at 12.45 g/d orally for at least 2 wk before TACE or RFA and those not receiving such pretreatment.A total of 270 patients with hepatocellular carcinoma complicated by cirrhosis were included in the study.Mean changes from baseline(Δ)in serum albumin(Alb),C-reactive protein(CRP),and transaminase levels,as well as peak body temperature were also determined and compared at days 2,5,and 10 after the start of TACE or RFA.RESULTS:In patients who underwent TACE or RFA,BCAA pre-intervention significantly suppressed the development of post-intervention hypoalbuminemia and reduced inflammatory reactions during the subsequent clinical course.After TACE,theΔAlb peaked on day 2,remained constantly lower in BCAA-treated patients,compared to the control group,and was-0.13±0.42g/dL in BCAA-treated patients and-0.33±0.51 g/dL in untreated patients on day 10.TheΔCRP was also significantly lower in BCAA-treated patients on days2,5 and 10 after TACE.Like the trends noted after TACE,a similar tendency was noted as to theΔAlb andΔCRP after RFA.The changes in serum Alb level were inversely correlated with CRP changes;therefore,a possible involvement of the anti-inflammatory effect of BCAAs was inferred as a factor contributory to the suppression of decrease in serum Alb level.CONCLUSION:Pre-intervention with BCAAs may hasten the recovery of serum Alb level and mitigate postoperative complications in patients undergoing TACE or RFA.
