AIM： To evaluate the effects of interferon-α-2b （IFN- α-2b） on expression of cyclooxygenase-2 （COX-2） and vascular endothelial growth factor （VEGF） in human hepatocellular carcinoma （HCC） inoculated in nude...AIM： To evaluate the effects of interferon-α-2b （IFN- α-2b） on expression of cyclooxygenase-2 （COX-2） and vascular endothelial growth factor （VEGF） in human hepatocellular carcinoma （HCC） inoculated in nude mice and to study the underlying mechanism of IFN-α- 2b against HCC growth. METHODS： Thirb/-two nude mice bearing human HCC were randomly divided into four groups （n = 8）. On the 10th day after implantation of HCC cells, the mice in test groups （groups A, B and C） received IFN-α- 2b at a serial dose （10000 IU for group A, 20000 IU for group B, 40000 IU for group C sc daily） for 35 d. The mice in control group received normal saline （NS）. The growth conditions of transplanted tumors were observed. Both genes and proteins of COX-2 and VEGF were detected by RT-PCR and Western blot. Apoptosis of tumor cells in nude mice was detected by TUNEL assay after treatment with IFN-α-2b. RESULTS： Tumors were significantly smaller and had a lower weight in the IFN-α-2b treatment groups than those in the control group （P 〈 0.01）, and the tumor growth inhibition rate in groups A, B and C was 27.78%, 65.22% and 49.64%, respectively. The expression levels of both genes and proteins of COX-2 and VEGF were much lower in the IFN-α-2b treatment groups than in the control group （P 〈 0.01）. The apoptosis index （AI） of tumor cells in the IFN-α-2b treatment groups was markedly higher than that in the control group （P 〈 0.01）. Group B had a higher inhibition rate of tumor growth, a lower expression level of COX-2 and VEGF and a higher AI than groups A and C （P 〈 0.05）, but there was no significant difference between groups A and C. CONCLUSION： The inhibitory effects of IFN-α-2b on implanted tumor growth and apoptosis may be associated with the down-regulation of COX-2 and VEGF expression. There is a dose-effect relationship. The medium dose of IFN-α-2b for inhibiting tumor growth is 20 000 IU/d.展开更多
Objective To investigate therelationships between serum concentration of insulin -like growth factor - I (IGF-I) and left ventricular function as well as coronary collateral circulation in patients with coronary arter...Objective To investigate therelationships between serum concentration of insulin -like growth factor - I (IGF-I) and left ventricular function as well as coronary collateral circulation in patients with coronary artery disease (CAD) . Methods In 41 patients with CAD and 15 control subjects without CAD, the concentrations of serum IGF - I were measured using radioimmunoassay. The relationships between the concentration of serum IGF - I and Leaman coronary artery score, Rentrop grade of coronary collateral circulation, left ventricular ejection fraction (LVEF) as well as left ventricular wall motion Cortina score were assessed. Results 1. There was no significant difference in the mean level of serum IGF -I between the CAD group and the control group (107. 92±44.74 ng/ml vs 113.05 ±33. 65 ng/ml, P> 0. 05), but the IGF - I concentrations in the subgroup with collateral circulation were significantly greater than that in the control group (147. 33 ±29. 92 ng/ml vs 113. 05±33. 65 ng/ml, P < 0. 01) or in the subgroup without collateral circulation (147. 33 ±29. 92 ng/ml vs 80. 01±29. 75 ng/ml , P < 0. 01). 2. The serum concentration of IGF -I had no significant correlation to the Leaman coronary artery score. 3. The serum level of IGF -I had significantly positive correlation to both LVEF ( r = 0. 45, P < 0. 001) and the Rentrop grade of coronary collateral circulation ( r = 0. 74, P < 0. 001), and was negatively related to the left ventricular wall motion Cortina score (r = -0. 53, P < 0. 001). 4. The Leaman coronary artery score had no significant correlation to the Rentrop grade of coronary collateral circulation. 5. The Leaman coronary artery score was related to neither the LVEF nor the Cortina score in the whole CAD group. In the subgroup without coronary collateral circulation, however, the Leaman score had significantly negative correlation to LVEF ( r = - 0. 46, P < 0. 05) and positive correlation to the Cortina score (r = 0. 47, P < 0. 05) . Conclusions The serum concentration of IGF -I was associated with both left ventricular function and coronary collateral circulation in patients with CAD. IGF -I may play a role in promoting coronary collateral circulation and in protecting left ventricular function in patients with coronary artery disease.展开更多
Background The present study aimed to investigate the detailed mode and specific sites for their binding as well as the functional relevance of this binding in the phenotypic proliferation of vascular smooth muscle ce...Background The present study aimed to investigate the detailed mode and specific sites for their binding as well as the functional relevance of this binding in the phenotypic proliferation of vascular smooth muscle cells(SMCs). Methods CREG knocked-down SMCs were employed to evaluate the biological activity of wtCREG and mCREG.Expressions of SMC differentiation markers SM myosin heavy chain(SM-MHC),SM-actin,heavy caldesmon and myocardin were determined by Western blotting using specific antibodies. Cellular growth of SMCs was assessed by bromide dewuridine (BrdU) incorporation and cell cycle analysis on fluorescence-activated cell sorting(FACS).A solid-phase binding assay was used to study the binding of CREG to extracellular domains of M6P/IGF2R.The cellular co-localization of the two recombinant CREGs with M6P/IGF2R was detected on SMC surface by immunoprecipitation and immunofluorescence analysis.Results The molecular weight of wtCREG was around 30 kD while that of the mCREG was～25 kD.Treatment of wtCREG with PNGase F reduced its molecular weight from～30 kD to～25 kD,whereas PNGase F treatment had no effect on the molecular weight of mCREG.Both wtCREG and mCREG proteins enhanced SMC differentiation,inhibited BrdU incorporation,and arrested cell cycle progression when added to the culture medium.In CREG knocked-down SMCs,the amount of CREG detected by immunoblotting in M6P/IGF2R immunoprecipitates was significantly reduced when compared to normal cells.Both recombinant CREGs co-immunoprecipitated with M6P/IGF2R, although slightly reduced amount of the mutant CREG was detected in M6P/IGF2R immunoprecipitates.Immunostaining revealed that His-tagged CREGs co-localized with IGF2R on the cell surface in a glycosylation-independent manner.In vitro binding assay showed that CREGs bound to M6P/ IGF2R extracellular domains 7-10 and 11-13 in a glycosylation -dependent and -independent manner,respectively.Further blocking experiments using soluble M6P/IGF2R fragments and M6P/IGF2R neutralizing antibody indicated that the biological activities of recombinant CREGs in SMC growth and the up-regulation of SMC differentiation markers were all abolished by treatment with the M6P/IGF2R neutralizing antibody. However,although the growth inhibitory effect of wtCREG was nearly abolished by D7-10 or D11-13,the effect of mCREG was only reversed by Dll-13,indicating that the binding to domains 11-13 is required for CREG to modulate the proliferation of SMCs.Conclusions These data suggest that solubleCREG proteins can exert their biological function via binding to the extracellular domains 7-10 and 11-13 of cell surface M6P/IGF2R in both a glycosylation-dependent and -independent manner.展开更多
Major aortopulmonary collateral arteries (MAPCAs) are congenital vessels that arise from the aorta or its first-order branches and are distally connected to the pulmonary arterial vasculature, thereby providing pulmon...Major aortopulmonary collateral arteries (MAPCAs) are congenital vessels that arise from the aorta or its first-order branches and are distally connected to the pulmonary arterial vasculature, thereby providing pulmonary blood flow. MAPCAs are often associated with cyanotic congenital heart disease with decreased pulmonary blood flow. Isolated MAPCAs are rare in patients without congenital heart disease with structurally normal hearts. Sometimes, isolated congenital MAPCAs can occur without any lung disease. Isolated MAPCAs represent the occurrence of collaterals in the absence of underlying heart disease, which commonly presents as heart failure, recurrent respiratory tract infection, and pulmonary artery hypertension. We report a rare case of congestive heart failure in a 6-year-old patient with dual arterial supply to an otherwise normal right lung, with a normal bronchial tree, and a structurally normal heart. The patient was successfully managed by the closure of collaterals by Amplatzer vascular plugs II (AVPII) and Amplatzer Piccolo Occluders.展开更多
Background:Pancreatic cancer is a malignant tumor of the gastrointestinal tract.Due to its insidious onset,most patients with newly diagnosed pancreatic cancer have missed the opportunity for radical surgery,which off...Background:Pancreatic cancer is a malignant tumor of the gastrointestinal tract.Due to its insidious onset,most patients with newly diagnosed pancreatic cancer have missed the opportunity for radical surgery,which offers patients the best chance of survival.The 5-year survival rate of patients with pancreatic cancer can be improved with early diagnosis,and serum tumor makers are an inexpensive and convenient diagnostic tool that is widely used in the diagnosis of malignancies.Objective:To determine the diagnostic value of vascular endothelial growth factor(VEGF),carbohydrate antigen 19-9(CA 19-9),and carcinoembryonic antigen(CEA)in patients with pancreatic cancer and the risk factors of vascular invasion.Methods:An experimental group comprising 52 patients with pancreatic cancer admitted to our department from July 2021 to July 2022 and a control group comprising 21 patients with benign pancreatic diseases during the same period were included in our study.Their serum VEGF,CA 19-9,and CEA levels were detected and compared between the two groups,and the correlation between the three markers in the invaded vessel and non-invaded vessel groups was investigated.The diagnostic value of a single tumor marker and in combination for pancreatic cancer was analyzed,and the three tumor marker levels of the experimental group in different pathological characteristics were detected and compared.Results:The experimental group had higher serum VEGF,CA 19-9,and CEA levels than the control group(P<0.05).Through a receiver operating characteristic(ROC)curve analysis,the combined detection had the highest value for the diagnosis of pancreatic cancer,in which the area under the curve(AUC)was 0.9158(95%CI:0.8415-0.9900),while the sensitivity and specificity were 76.19%and 98.08%,respectively.Serum VEGF and CA 19-9 levels were higher in stage Ⅲ-Ⅳ pancreatic cancer patients and those with tumor metastasis compared with stage Ⅰ-Ⅱ patients and those without metastasis(P<0.05),respectively.Binary logistic regression analysis was performed to determine the risk factors of vascular invasion in pancreatic cancer,and the results showed that only serum VEGF was a risk factor(P<0.05),OR(95%CI):1.001-1.006.Conclusion:Patients with pancreatic cancer have significantly higher serum VEGF,CA 19-9,and CEA levels,and the combined detection of tumor markers is of high clinical value in its diagnosis.In addition,serum VEGF is an independent risk factor of vascular invasion in pancreatic cancer,which can predict vascular invasion to a certain extent.展开更多
基金Supported by Clinical Key Program Point Subject Foundation of Ministry of Public Health, No. 20012434
文摘AIM： To evaluate the effects of interferon-α-2b （IFN- α-2b） on expression of cyclooxygenase-2 （COX-2） and vascular endothelial growth factor （VEGF） in human hepatocellular carcinoma （HCC） inoculated in nude mice and to study the underlying mechanism of IFN-α- 2b against HCC growth. METHODS： Thirb/-two nude mice bearing human HCC were randomly divided into four groups （n = 8）. On the 10th day after implantation of HCC cells, the mice in test groups （groups A, B and C） received IFN-α- 2b at a serial dose （10000 IU for group A, 20000 IU for group B, 40000 IU for group C sc daily） for 35 d. The mice in control group received normal saline （NS）. The growth conditions of transplanted tumors were observed. Both genes and proteins of COX-2 and VEGF were detected by RT-PCR and Western blot. Apoptosis of tumor cells in nude mice was detected by TUNEL assay after treatment with IFN-α-2b. RESULTS： Tumors were significantly smaller and had a lower weight in the IFN-α-2b treatment groups than those in the control group （P 〈 0.01）, and the tumor growth inhibition rate in groups A, B and C was 27.78%, 65.22% and 49.64%, respectively. The expression levels of both genes and proteins of COX-2 and VEGF were much lower in the IFN-α-2b treatment groups than in the control group （P 〈 0.01）. The apoptosis index （AI） of tumor cells in the IFN-α-2b treatment groups was markedly higher than that in the control group （P 〈 0.01）. Group B had a higher inhibition rate of tumor growth, a lower expression level of COX-2 and VEGF and a higher AI than groups A and C （P 〈 0.05）, but there was no significant difference between groups A and C. CONCLUSION： The inhibitory effects of IFN-α-2b on implanted tumor growth and apoptosis may be associated with the down-regulation of COX-2 and VEGF expression. There is a dose-effect relationship. The medium dose of IFN-α-2b for inhibiting tumor growth is 20 000 IU/d.
文摘Objective To investigate therelationships between serum concentration of insulin -like growth factor - I (IGF-I) and left ventricular function as well as coronary collateral circulation in patients with coronary artery disease (CAD) . Methods In 41 patients with CAD and 15 control subjects without CAD, the concentrations of serum IGF - I were measured using radioimmunoassay. The relationships between the concentration of serum IGF - I and Leaman coronary artery score, Rentrop grade of coronary collateral circulation, left ventricular ejection fraction (LVEF) as well as left ventricular wall motion Cortina score were assessed. Results 1. There was no significant difference in the mean level of serum IGF -I between the CAD group and the control group (107. 92±44.74 ng/ml vs 113.05 ±33. 65 ng/ml, P> 0. 05), but the IGF - I concentrations in the subgroup with collateral circulation were significantly greater than that in the control group (147. 33 ±29. 92 ng/ml vs 113. 05±33. 65 ng/ml, P < 0. 01) or in the subgroup without collateral circulation (147. 33 ±29. 92 ng/ml vs 80. 01±29. 75 ng/ml , P < 0. 01). 2. The serum concentration of IGF -I had no significant correlation to the Leaman coronary artery score. 3. The serum level of IGF -I had significantly positive correlation to both LVEF ( r = 0. 45, P < 0. 001) and the Rentrop grade of coronary collateral circulation ( r = 0. 74, P < 0. 001), and was negatively related to the left ventricular wall motion Cortina score (r = -0. 53, P < 0. 001). 4. The Leaman coronary artery score had no significant correlation to the Rentrop grade of coronary collateral circulation. 5. The Leaman coronary artery score was related to neither the LVEF nor the Cortina score in the whole CAD group. In the subgroup without coronary collateral circulation, however, the Leaman score had significantly negative correlation to LVEF ( r = - 0. 46, P < 0. 05) and positive correlation to the Cortina score (r = 0. 47, P < 0. 05) . Conclusions The serum concentration of IGF -I was associated with both left ventricular function and coronary collateral circulation in patients with CAD. IGF -I may play a role in promoting coronary collateral circulation and in protecting left ventricular function in patients with coronary artery disease.
文摘Background The present study aimed to investigate the detailed mode and specific sites for their binding as well as the functional relevance of this binding in the phenotypic proliferation of vascular smooth muscle cells(SMCs). Methods CREG knocked-down SMCs were employed to evaluate the biological activity of wtCREG and mCREG.Expressions of SMC differentiation markers SM myosin heavy chain(SM-MHC),SM-actin,heavy caldesmon and myocardin were determined by Western blotting using specific antibodies. Cellular growth of SMCs was assessed by bromide dewuridine (BrdU) incorporation and cell cycle analysis on fluorescence-activated cell sorting(FACS).A solid-phase binding assay was used to study the binding of CREG to extracellular domains of M6P/IGF2R.The cellular co-localization of the two recombinant CREGs with M6P/IGF2R was detected on SMC surface by immunoprecipitation and immunofluorescence analysis.Results The molecular weight of wtCREG was around 30 kD while that of the mCREG was～25 kD.Treatment of wtCREG with PNGase F reduced its molecular weight from～30 kD to～25 kD,whereas PNGase F treatment had no effect on the molecular weight of mCREG.Both wtCREG and mCREG proteins enhanced SMC differentiation,inhibited BrdU incorporation,and arrested cell cycle progression when added to the culture medium.In CREG knocked-down SMCs,the amount of CREG detected by immunoblotting in M6P/IGF2R immunoprecipitates was significantly reduced when compared to normal cells.Both recombinant CREGs co-immunoprecipitated with M6P/IGF2R, although slightly reduced amount of the mutant CREG was detected in M6P/IGF2R immunoprecipitates.Immunostaining revealed that His-tagged CREGs co-localized with IGF2R on the cell surface in a glycosylation-independent manner.In vitro binding assay showed that CREGs bound to M6P/ IGF2R extracellular domains 7-10 and 11-13 in a glycosylation -dependent and -independent manner,respectively.Further blocking experiments using soluble M6P/IGF2R fragments and M6P/IGF2R neutralizing antibody indicated that the biological activities of recombinant CREGs in SMC growth and the up-regulation of SMC differentiation markers were all abolished by treatment with the M6P/IGF2R neutralizing antibody. However,although the growth inhibitory effect of wtCREG was nearly abolished by D7-10 or D11-13,the effect of mCREG was only reversed by Dll-13,indicating that the binding to domains 11-13 is required for CREG to modulate the proliferation of SMCs.Conclusions These data suggest that solubleCREG proteins can exert their biological function via binding to the extracellular domains 7-10 and 11-13 of cell surface M6P/IGF2R in both a glycosylation-dependent and -independent manner.
文摘Major aortopulmonary collateral arteries (MAPCAs) are congenital vessels that arise from the aorta or its first-order branches and are distally connected to the pulmonary arterial vasculature, thereby providing pulmonary blood flow. MAPCAs are often associated with cyanotic congenital heart disease with decreased pulmonary blood flow. Isolated MAPCAs are rare in patients without congenital heart disease with structurally normal hearts. Sometimes, isolated congenital MAPCAs can occur without any lung disease. Isolated MAPCAs represent the occurrence of collaterals in the absence of underlying heart disease, which commonly presents as heart failure, recurrent respiratory tract infection, and pulmonary artery hypertension. We report a rare case of congestive heart failure in a 6-year-old patient with dual arterial supply to an otherwise normal right lung, with a normal bronchial tree, and a structurally normal heart. The patient was successfully managed by the closure of collaterals by Amplatzer vascular plugs II (AVPII) and Amplatzer Piccolo Occluders.
文摘Background:Pancreatic cancer is a malignant tumor of the gastrointestinal tract.Due to its insidious onset,most patients with newly diagnosed pancreatic cancer have missed the opportunity for radical surgery,which offers patients the best chance of survival.The 5-year survival rate of patients with pancreatic cancer can be improved with early diagnosis,and serum tumor makers are an inexpensive and convenient diagnostic tool that is widely used in the diagnosis of malignancies.Objective:To determine the diagnostic value of vascular endothelial growth factor(VEGF),carbohydrate antigen 19-9(CA 19-9),and carcinoembryonic antigen(CEA)in patients with pancreatic cancer and the risk factors of vascular invasion.Methods:An experimental group comprising 52 patients with pancreatic cancer admitted to our department from July 2021 to July 2022 and a control group comprising 21 patients with benign pancreatic diseases during the same period were included in our study.Their serum VEGF,CA 19-9,and CEA levels were detected and compared between the two groups,and the correlation between the three markers in the invaded vessel and non-invaded vessel groups was investigated.The diagnostic value of a single tumor marker and in combination for pancreatic cancer was analyzed,and the three tumor marker levels of the experimental group in different pathological characteristics were detected and compared.Results:The experimental group had higher serum VEGF,CA 19-9,and CEA levels than the control group(P<0.05).Through a receiver operating characteristic(ROC)curve analysis,the combined detection had the highest value for the diagnosis of pancreatic cancer,in which the area under the curve(AUC)was 0.9158(95%CI:0.8415-0.9900),while the sensitivity and specificity were 76.19%and 98.08%,respectively.Serum VEGF and CA 19-9 levels were higher in stage Ⅲ-Ⅳ pancreatic cancer patients and those with tumor metastasis compared with stage Ⅰ-Ⅱ patients and those without metastasis(P<0.05),respectively.Binary logistic regression analysis was performed to determine the risk factors of vascular invasion in pancreatic cancer,and the results showed that only serum VEGF was a risk factor(P<0.05),OR(95%CI):1.001-1.006.Conclusion:Patients with pancreatic cancer have significantly higher serum VEGF,CA 19-9,and CEA levels,and the combined detection of tumor markers is of high clinical value in its diagnosis.In addition,serum VEGF is an independent risk factor of vascular invasion in pancreatic cancer,which can predict vascular invasion to a certain extent.
