Background:Intrahepatic cholestasis of pregnancy(ICP)increases the risk of adverse pregnancy outcomes.This study aimed to explore the association between serum syndecan-1 and glypican-3 levels and the adverse perinata...Background:Intrahepatic cholestasis of pregnancy(ICP)increases the risk of adverse pregnancy outcomes.This study aimed to explore the association between serum syndecan-1 and glypican-3 levels and the adverse perinatal outcome as well as the responses to the treatment of ursodeoxycholic acid(UDCA).Methods:This prospective,case control study included 88 pregnant women(44 women with ICP and 44 healthy controls).The primary end points were the perinatal outcome and the response to UDCA therapy.A logistic regression model was used to identify the independent risk factors of adverse pregnancy outcomes and reduced response to UDCA therapy.Results:Women with ICP had significantly higher serum syndecan-1(1.27±0.36 ng/m L vs.0.98±0.50 ng/m L;P=0.003),glypican-3(1.78±0.13 ng/m L vs.1.69±0.16 ng/m L;P=0.004),AST(128.59±1.44 vs.13.29±1.32 U/L;P<0.001),and ALT(129.84±1.53 vs.8.00±3.67 U/L;P<0.001)levels compared with the controls.The increased levels of syndecan-1(OR=4.715,95%CI:1.554–14.310;P=0.006),glypican-3(OR=8.465,95%CI:3.372–21.248;P=0.007),ALT(OR=1.382,95%CI:1.131–1.690;P=0.002),and postprandial bile acid(PBA)(OR=3.392,95%CI:1.003–12.869;P=0.026)were correlated to ICP.The adverse neonatal outcome was related to increased glypican-3(OR=4.275,95%CI:2.726–5.635;P=0.039),and PBA(OR=3.026,95%CI:1.069–13.569;P=0.037).Increases of syndecan-1(OR=7.464,95%CI:2.130–26.153,P=0.017)and glypican-3(OR=6.194,95%CI:2.951–13.002;P=0.025)were the risk factors of decreased response to UDCA treatment.Conclusion:Syndecan-1 and glypican-3 might be powerful determinants in predicting adverse perinatal outcome in patients with ICP,and they can be used to predict the response to the UDCA treatment.展开更多
Objective:To induce potent CD8^+T-cells against glypican-3(GPC3),which is overexpressed in hepatocellular carcinoma(HCC),to suspend tumor development.Methods:Since the chemokine receptor XCR1 is selectively expressed ...Objective:To induce potent CD8^+T-cells against glypican-3(GPC3),which is overexpressed in hepatocellular carcinoma(HCC),to suspend tumor development.Methods:Since the chemokine receptor XCR1 is selectively expressed on professional cross-presenting CD8α^+dendritic cells(DCs).展开更多
BACKGROUND Individuals within specific risk groups for pancreatic ductal adenocarcinoma(PDAC)[mucinous cystic lesions(MCLs),hereditary risk(HR),and new-late onset diabetes mellitus(NLOD)]represent an opportunity for e...BACKGROUND Individuals within specific risk groups for pancreatic ductal adenocarcinoma(PDAC)[mucinous cystic lesions(MCLs),hereditary risk(HR),and new-late onset diabetes mellitus(NLOD)]represent an opportunity for early cancer detection.Endoscopic ultrasound(EUS)is a premium image modality for PDAC screening and precursor lesion characterization.While no specific biomarker is currently clinically available for this purpose,glypican-1(GPC1)is overexpressed in the circulating exosomes(crExos)of patients with PDAC compared with healthy subjects or those harboring benign pancreatic diseases.AIM To evaluate the capacity of GPC1+crExos to identify individuals at higher risk within these specific groups,all characterized by EUS.METHODS This cross-sectional study with a prospective unicentric cohort included 88 subjects:40 patients with MCL,20 individuals with HR,and 20 patients with NLOD.A control group(CG)was submitted to EUS for other reasons than pancreatic pathology,with normal pancreas and absence of hereditary risk factors(n=8).The inclusion period was between October 2016 and January 2019,and the study was approved by the Ethics Committee of Centro Hospitalar Universitário de São João,Porto,Portugal.All patients provided written informed consent.EUS and blood tests for quantification of GPC1+crExos by flow cytometry and carbohydrate antigen 19-9(CA 19-9)levels by ELISA were performed in all subjects.EUS-guided tissue acquisition was done whenever necessary.For statistical analysis,SPSS®27.0(IBM Corp.,Armonk,NY,United States)version was used.All graphs were created using GraphPad Prism 7.00(GraphPad Software,San Diego,CA,United States).RESULTS Half of MCLs harbored worrisome features(WF)or high-risk stigmata(HRS).Pancreatic abnormalities were detected by EUS in 10.0%and 35.0%in HR and NLOD individuals,respectively,all considered non-malignant and“harmless.”Median levels of GPC1+crExos were statistically different:MCL[99.4%,interquartile range(IQR):94.9%-99.8%],HR(82.0%,IQR:28.9%-98.2%),NLOD(12.6%,IQR:5.2%-63.4%),and CG(16.2%,IQR:6.6%-20.1%)(P<0.0001).Median levels of CA 19-9 were within the normal range in all groups(standard clinical cut-off of 37 U/mL).Within HR,individuals with a positive history of cancer had higher median levels of GPC1+crExos(97.9%;IQR:61.7%-99.5%),compared to those without(59.7%;IQR:26.3%-96.4%),despite no statistical significance(P=0.21).Pancreatic cysts with WF/HRS were statistically associated with higher median levels of GPC1+crExos(99.6%;IQR:97.6%-99.8%)compared to those without(96.5%;IQR:81.3%-99.5%)(P=0.011),presenting an area under the receiver operating characteristic curve value of 0.723(sensitivity 75.0%and specificity 67.7%,using a cutoff of 98.5%;P=0.012).CONCLUSION GPC1+crExos may act as biomarker to support the diagnosis and stratification of PDAC precursor lesions,and in signaling individuals with genetic predisposition in the absence of EUS abnormalities.展开更多
基金the Ethics Committee of the Liv Hospital Affiliated to University of I˙stinye,Turkey(2018-003/015).
文摘Background:Intrahepatic cholestasis of pregnancy(ICP)increases the risk of adverse pregnancy outcomes.This study aimed to explore the association between serum syndecan-1 and glypican-3 levels and the adverse perinatal outcome as well as the responses to the treatment of ursodeoxycholic acid(UDCA).Methods:This prospective,case control study included 88 pregnant women(44 women with ICP and 44 healthy controls).The primary end points were the perinatal outcome and the response to UDCA therapy.A logistic regression model was used to identify the independent risk factors of adverse pregnancy outcomes and reduced response to UDCA therapy.Results:Women with ICP had significantly higher serum syndecan-1(1.27±0.36 ng/m L vs.0.98±0.50 ng/m L;P=0.003),glypican-3(1.78±0.13 ng/m L vs.1.69±0.16 ng/m L;P=0.004),AST(128.59±1.44 vs.13.29±1.32 U/L;P<0.001),and ALT(129.84±1.53 vs.8.00±3.67 U/L;P<0.001)levels compared with the controls.The increased levels of syndecan-1(OR=4.715,95%CI:1.554–14.310;P=0.006),glypican-3(OR=8.465,95%CI:3.372–21.248;P=0.007),ALT(OR=1.382,95%CI:1.131–1.690;P=0.002),and postprandial bile acid(PBA)(OR=3.392,95%CI:1.003–12.869;P=0.026)were correlated to ICP.The adverse neonatal outcome was related to increased glypican-3(OR=4.275,95%CI:2.726–5.635;P=0.039),and PBA(OR=3.026,95%CI:1.069–13.569;P=0.037).Increases of syndecan-1(OR=7.464,95%CI:2.130–26.153,P=0.017)and glypican-3(OR=6.194,95%CI:2.951–13.002;P=0.025)were the risk factors of decreased response to UDCA treatment.Conclusion:Syndecan-1 and glypican-3 might be powerful determinants in predicting adverse perinatal outcome in patients with ICP,and they can be used to predict the response to the UDCA treatment.
文摘Objective:To induce potent CD8^+T-cells against glypican-3(GPC3),which is overexpressed in hepatocellular carcinoma(HCC),to suspend tumor development.Methods:Since the chemokine receptor XCR1 is selectively expressed on professional cross-presenting CD8α^+dendritic cells(DCs).
基金Supported by Guilherme Macedo team was supported by the Portuguese Society of Digestive Endoscopy(SPED)2017 Research Grant,No.SG/CHSJ-A2017Norte Portugal Regional Programme(NORTE 2020)under the PORTUGAL 2020 Partnership Agreement through the European Regional Development Fund(ERDF)to Sonia A Melo,No.NORTE-01-0145-FEDER-000029+1 种基金National Funds through Foundation for Science and Technology(FCT)to Sonia A Melo,No.POCI-01-0145-FEDER-32189Foundation for Science and Technology(FCT)to Bárbara Adem and Ines A Batista,No.PD/BD/135546/2018 and No.SFRH/BD/144854/2019.
文摘BACKGROUND Individuals within specific risk groups for pancreatic ductal adenocarcinoma(PDAC)[mucinous cystic lesions(MCLs),hereditary risk(HR),and new-late onset diabetes mellitus(NLOD)]represent an opportunity for early cancer detection.Endoscopic ultrasound(EUS)is a premium image modality for PDAC screening and precursor lesion characterization.While no specific biomarker is currently clinically available for this purpose,glypican-1(GPC1)is overexpressed in the circulating exosomes(crExos)of patients with PDAC compared with healthy subjects or those harboring benign pancreatic diseases.AIM To evaluate the capacity of GPC1+crExos to identify individuals at higher risk within these specific groups,all characterized by EUS.METHODS This cross-sectional study with a prospective unicentric cohort included 88 subjects:40 patients with MCL,20 individuals with HR,and 20 patients with NLOD.A control group(CG)was submitted to EUS for other reasons than pancreatic pathology,with normal pancreas and absence of hereditary risk factors(n=8).The inclusion period was between October 2016 and January 2019,and the study was approved by the Ethics Committee of Centro Hospitalar Universitário de São João,Porto,Portugal.All patients provided written informed consent.EUS and blood tests for quantification of GPC1+crExos by flow cytometry and carbohydrate antigen 19-9(CA 19-9)levels by ELISA were performed in all subjects.EUS-guided tissue acquisition was done whenever necessary.For statistical analysis,SPSS®27.0(IBM Corp.,Armonk,NY,United States)version was used.All graphs were created using GraphPad Prism 7.00(GraphPad Software,San Diego,CA,United States).RESULTS Half of MCLs harbored worrisome features(WF)or high-risk stigmata(HRS).Pancreatic abnormalities were detected by EUS in 10.0%and 35.0%in HR and NLOD individuals,respectively,all considered non-malignant and“harmless.”Median levels of GPC1+crExos were statistically different:MCL[99.4%,interquartile range(IQR):94.9%-99.8%],HR(82.0%,IQR:28.9%-98.2%),NLOD(12.6%,IQR:5.2%-63.4%),and CG(16.2%,IQR:6.6%-20.1%)(P<0.0001).Median levels of CA 19-9 were within the normal range in all groups(standard clinical cut-off of 37 U/mL).Within HR,individuals with a positive history of cancer had higher median levels of GPC1+crExos(97.9%;IQR:61.7%-99.5%),compared to those without(59.7%;IQR:26.3%-96.4%),despite no statistical significance(P=0.21).Pancreatic cysts with WF/HRS were statistically associated with higher median levels of GPC1+crExos(99.6%;IQR:97.6%-99.8%)compared to those without(96.5%;IQR:81.3%-99.5%)(P=0.011),presenting an area under the receiver operating characteristic curve value of 0.723(sensitivity 75.0%and specificity 67.7%,using a cutoff of 98.5%;P=0.012).CONCLUSION GPC1+crExos may act as biomarker to support the diagnosis and stratification of PDAC precursor lesions,and in signaling individuals with genetic predisposition in the absence of EUS abnormalities.
