BACKGROUND: The manipulation of immunosuppression therapy remains challenging in patients who develop infectious diseases or multiple organ dysfunction after liver transplantation.We evaluated the outcomes of delayed ...BACKGROUND: The manipulation of immunosuppression therapy remains challenging in patients who develop infectious diseases or multiple organ dysfunction after liver transplantation.We evaluated the outcomes of delayed introduction of immunosuppression in the patients after liver transplantation under immune monitoring with Immu Know assay.METHODS: From March 2009 to February 2014, 225 consecutive liver recipients in our institute were included. The delayed administration of immunosuppressive regimens was attempted in 11 liver recipients with multiple severe comorbidities.RESULTS: The median duration of non-immunosuppression was 12 days(range 5-58). Due to the infectious complications,the serial Immu Know assay showed a significantly low ATP level of 64±35 ng/mL in the early period after transplantation. With the development of comorbidities, the Immu Know value significantly increased. However, the acute allograft rejection developed when a continuous distinct elevation of both ATP and glutamyltranspeptidase levels was detected.The average ATP level measured just before the development of acute rejection was 271±115 ng/mL.CONCLUSIONS: The delayed introduction of immunosuppressive regimens is safe and effective in management of critically ill patients after liver transplantation. The serial Immu Know assay could provide a reliable depiction of the dynamics of functional immunity throughout the clinical course of a given patient.展开更多
BACKGROUND Glycolysis caused by hypoxia-induced abnormal activation of hypoxia inducible factor-1α(HIF-1α)in the immune microenvironment promotes the progression of hepatocellular carcinoma(HCC),leading to enhanced ...BACKGROUND Glycolysis caused by hypoxia-induced abnormal activation of hypoxia inducible factor-1α(HIF-1α)in the immune microenvironment promotes the progression of hepatocellular carcinoma(HCC),leading to enhanced drug resistance in cancer cells.Therefore,altering the immunosuppressive microenvironment by improving the hypoxic state is a new goal in improving cancer treatment.AIM To analyse the role of HIF-1α,which is closely related to tumour proliferation,invasion,metastasis,and angiogenesis,in the proliferation and invasion of liver cancer,and to explore the HIF-1αpathway-mediated anti-cancer mechanism of sirolimus(SRL)combined with Huai Er.METHODS Previous studies on HCC tissues identified the importance of HIF-1α,glucose transporter 1(GLUT1),and lactate dehydrogenase A(LDHA)expression.In this study,HepG2 and Huh7 cell lines were treated,under hypoxic and normoxic conditions,with a combination of SRL and Huai Er.The effects on proliferation,invasion,cell cycle,and apoptosis were analysed.Proteomics and genomics techniques were used to analyze the HIF-1α-related signalling pathway during SRL combined with Huai Er treatment and its inhibition of the proliferation of HCC cells.RESULTS High levels of HIF-1α,LDHA,and GLUT-1 were found in poorly differentiated HCC,with lower patient survival rates.Hypoxia promoted the proliferation of HepG2 and Huh7 cells and weakened the apoptosis and cell cycle blocking effects of the SRL/Huai Er treatment.This was achieved by activation of HIF-1αand glycolysis in HCC,leading to the upregulation of LDHA,GLUT-1,Akt/mammalian target of rapamycin(mTOR),vascular endothelial growth factor(VEGF),and Forkhead box P3 and downregulation of phosphatase and tensin homolog deleted on chromosome ten(PTEN)and p27.The hypoxia-induced activation of HIF-1αshowed the greatest attenuation in the SRL/Huai Er(S50+H8)group compared to the drug treatments alone(P<0.001).The S50+H8 treatment significantly downregulated the expression of mTOR and HIF-1α,and significantly reduced the expression of VEGF mRNA.Meanwhile,the combined blocking of mTOR and HIF-1αenhanced the downregulation of Akt/mTOR,HIF-1α,LDHA,and GLUT-1 mRNA and resulted in the downregulation of PTEN,p27,and VEGF mRNA(P<0.001).CONCLUSION SRL increases the anti-cancer effect of Huai Er,which reduces the promotion of hypoxia-induced HIF-1αon the Warburg effect by inhibition of the PI3K/Akt/mTOR-HIF-1αand HIF-1α-PTEN signalling pathways in HCC.展开更多
Objective:Pancreatic ductal adenocarcinoma cancer(PDAC)is one of the leading causes of cancer-related death worldwide.Hence,the development of effective anti-PDAC therapies is urgently required.Patient-derived xenogra...Objective:Pancreatic ductal adenocarcinoma cancer(PDAC)is one of the leading causes of cancer-related death worldwide.Hence,the development of effective anti-PDAC therapies is urgently required.Patient-derived xenograft(PDX)models are useful models for developing anti-cancer therapies and screening drugs for pre&sion medicine.This review aimed to provide an updated summary of using PDX models in PDAC.Data sources:The author retrieved information from the PubMed database up to June 2019 using various combinations of search terms,including PDAC,pancreatic carcinoma,pancreatic cancer,patient-derived xenografts or PDX,and patient-derived tumor xenografts or PDTX.Study selection:Original articles and review articles relevant to the review's theme were selected.Results:PDX models are better than cell line-derived xenograft and other models.PDX models consistently demonstrate retained tumor morphology and genetic stability,are benefi&al in cancer research,could enhance drug discovery and oncologic mechanism development of PDAC,allow an improved understanding of human cancer cell biology,and help guide personalized treatmem.Conclusions:In this review,we outline the status and application of PDX models in both basic and pre-clinical pancreatic cancer researches.PDX model is one of the most appropriate pre-clinical tools that can improve the prognosis of patients with pancreatic cancer in the future.展开更多
文摘BACKGROUND: The manipulation of immunosuppression therapy remains challenging in patients who develop infectious diseases or multiple organ dysfunction after liver transplantation.We evaluated the outcomes of delayed introduction of immunosuppression in the patients after liver transplantation under immune monitoring with Immu Know assay.METHODS: From March 2009 to February 2014, 225 consecutive liver recipients in our institute were included. The delayed administration of immunosuppressive regimens was attempted in 11 liver recipients with multiple severe comorbidities.RESULTS: The median duration of non-immunosuppression was 12 days(range 5-58). Due to the infectious complications,the serial Immu Know assay showed a significantly low ATP level of 64±35 ng/mL in the early period after transplantation. With the development of comorbidities, the Immu Know value significantly increased. However, the acute allograft rejection developed when a continuous distinct elevation of both ATP and glutamyltranspeptidase levels was detected.The average ATP level measured just before the development of acute rejection was 271±115 ng/mL.CONCLUSIONS: The delayed introduction of immunosuppressive regimens is safe and effective in management of critically ill patients after liver transplantation. The serial Immu Know assay could provide a reliable depiction of the dynamics of functional immunity throughout the clinical course of a given patient.
基金Supported by the Natural Science Foundation of Capital Medical University,No.PYZ20014 and No.PYZ21074。
文摘BACKGROUND Glycolysis caused by hypoxia-induced abnormal activation of hypoxia inducible factor-1α(HIF-1α)in the immune microenvironment promotes the progression of hepatocellular carcinoma(HCC),leading to enhanced drug resistance in cancer cells.Therefore,altering the immunosuppressive microenvironment by improving the hypoxic state is a new goal in improving cancer treatment.AIM To analyse the role of HIF-1α,which is closely related to tumour proliferation,invasion,metastasis,and angiogenesis,in the proliferation and invasion of liver cancer,and to explore the HIF-1αpathway-mediated anti-cancer mechanism of sirolimus(SRL)combined with Huai Er.METHODS Previous studies on HCC tissues identified the importance of HIF-1α,glucose transporter 1(GLUT1),and lactate dehydrogenase A(LDHA)expression.In this study,HepG2 and Huh7 cell lines were treated,under hypoxic and normoxic conditions,with a combination of SRL and Huai Er.The effects on proliferation,invasion,cell cycle,and apoptosis were analysed.Proteomics and genomics techniques were used to analyze the HIF-1α-related signalling pathway during SRL combined with Huai Er treatment and its inhibition of the proliferation of HCC cells.RESULTS High levels of HIF-1α,LDHA,and GLUT-1 were found in poorly differentiated HCC,with lower patient survival rates.Hypoxia promoted the proliferation of HepG2 and Huh7 cells and weakened the apoptosis and cell cycle blocking effects of the SRL/Huai Er treatment.This was achieved by activation of HIF-1αand glycolysis in HCC,leading to the upregulation of LDHA,GLUT-1,Akt/mammalian target of rapamycin(mTOR),vascular endothelial growth factor(VEGF),and Forkhead box P3 and downregulation of phosphatase and tensin homolog deleted on chromosome ten(PTEN)and p27.The hypoxia-induced activation of HIF-1αshowed the greatest attenuation in the SRL/Huai Er(S50+H8)group compared to the drug treatments alone(P<0.001).The S50+H8 treatment significantly downregulated the expression of mTOR and HIF-1α,and significantly reduced the expression of VEGF mRNA.Meanwhile,the combined blocking of mTOR and HIF-1αenhanced the downregulation of Akt/mTOR,HIF-1α,LDHA,and GLUT-1 mRNA and resulted in the downregulation of PTEN,p27,and VEGF mRNA(P<0.001).CONCLUSION SRL increases the anti-cancer effect of Huai Er,which reduces the promotion of hypoxia-induced HIF-1αon the Warburg effect by inhibition of the PI3K/Akt/mTOR-HIF-1αand HIF-1α-PTEN signalling pathways in HCC.
文摘Objective:Pancreatic ductal adenocarcinoma cancer(PDAC)is one of the leading causes of cancer-related death worldwide.Hence,the development of effective anti-PDAC therapies is urgently required.Patient-derived xenograft(PDX)models are useful models for developing anti-cancer therapies and screening drugs for pre&sion medicine.This review aimed to provide an updated summary of using PDX models in PDAC.Data sources:The author retrieved information from the PubMed database up to June 2019 using various combinations of search terms,including PDAC,pancreatic carcinoma,pancreatic cancer,patient-derived xenografts or PDX,and patient-derived tumor xenografts or PDTX.Study selection:Original articles and review articles relevant to the review's theme were selected.Results:PDX models are better than cell line-derived xenograft and other models.PDX models consistently demonstrate retained tumor morphology and genetic stability,are benefi&al in cancer research,could enhance drug discovery and oncologic mechanism development of PDAC,allow an improved understanding of human cancer cell biology,and help guide personalized treatmem.Conclusions:In this review,we outline the status and application of PDX models in both basic and pre-clinical pancreatic cancer researches.PDX model is one of the most appropriate pre-clinical tools that can improve the prognosis of patients with pancreatic cancer in the future.
