Objective:To investigate the expressions of plasminogen activator inhibitor type 1 (PAI-1), C-erbB-2, VEGF and Ki-67 by immunohistostaining and then to evaluate the prognostic value of PAI-1 in node-negative breast ca...Objective:To investigate the expressions of plasminogen activator inhibitor type 1 (PAI-1), C-erbB-2, VEGF and Ki-67 by immunohistostaining and then to evaluate the prognostic value of PAI-1 in node-negative breast cancer. Methods:The study included a retrospective series of 62 female patients with axillary lymph node-negative breast cancer. Expressions of PAI-1, C-erbB-2, VEGF and Ki-67 were determined by immunohistostaining on formalin-fixed paraffin-embedded tissue sections from these patients after a median follow-up of 69 months (range 22–117 months). Correlations with well known clinicopathologic factors were assessed and multivariate survival analyses were performed. Results: High PAI-1 level was positively associated with high histologic grade of the tumors. Disease-free survival (DFS) was significantly shorter for the patients with moderate to intensive expression of PAI-1 than for those with negative (χ2 = 25.46, P < 0.001; χ2 = 23.07, P < 0.001) to mild expression (χ2 = 19.75, P < 0.001; χ2 = 17.40, P < 0.001). Although on univariate analysis of the prognostic factors, tumor size, location of primary tumor and age as well as expressions of PAI-1, VEGF and Ki-67 were all significantly prognostic factors for DFS (P < 0.05), PAI-1 was the only independent prognostic factor on multivariate analysis (P<0.0001; hazard ratio [HR], 4.041; 95% confidence interval [CI], 1.928–8.468). Conclusion: These results of the current study indicate that intermediate or high expression of PAI-1 represents a strong and independent unfavorable prognostic factor for the de-velopment of recurrence or metastases in axillary node-negative breast cancer.展开更多
In this study,37 derivatives of phorbol esters were synthesized and their anti-HIV-1 activities evaluated,building upon our previous synthesis of 51 phorbol derivatives.12-Para-electron-acceptor-trans-cinnamoyl-13-dec...In this study,37 derivatives of phorbol esters were synthesized and their anti-HIV-1 activities evaluated,building upon our previous synthesis of 51 phorbol derivatives.12-Para-electron-acceptor-trans-cinnamoyl-13-decanoyl phorbol derivatives stood out,demonstrating remarkable anti-HIV-1 activities and inhibitory effects on syncytia formation.These derivatives exhibited a higher safety index compared with the positive control drug.Among them,12-(trans-4-fluorocinnamoyl)-13-decanoyl phorbol,designated as compound 3c,exhibited the most potent anti-HIV-1 activity(EC_(50)2.9 nmol·L^(−1),CC50/EC_(50)11117.24)and significantly inhibited the formation of syncytium(EC_(50)7.0 nmol·L^(−1),CC50/EC_(50)4891.43).Moreover,compound 3c is hypothesized to act both as an HIV-1 entry inhibitor and as an HIV-1 reverse transcriptase inhibitor.Isothermal titration calorimetry and molecular docking studies indicated that compound 3c may also function as a natural activator of protein kinase C(PKC).Therefore,compound 3c emerges as a potential candidate for developing new anti-HIV drugs.展开更多
随着糖皮质激素在临床的广泛应用，激素性股骨头坏死（steroid-induced osteonecrosis of the femoral head，SONFH）成为非创伤性股骨头坏死（ osteonecrosis of the femoral head，ONFH）的主要原因，约占非创伤性ONFH的2／3。长期接...随着糖皮质激素在临床的广泛应用，激素性股骨头坏死（steroid-induced osteonecrosis of the femoral head，SONFH）成为非创伤性股骨头坏死（ osteonecrosis of the femoral head，ONFH）的主要原因，约占非创伤性ONFH的2／3。长期接受糖皮质激素治疗或接受大剂量糖皮质激素冲击治疗的患者中，9％～40％可能会发生SONFH，同时伴有糖皮质激素诱导的骨质疏松。随着基因组学的发展，发现SONFH的发生与纤溶酶原激活物抑制物-1（ plasminogen activator inhibitor-1，PAI-1）和三磷酸腺苷黏合转运体B1（adenosine triphosphate binding cassette B1，ABCB1）的基因多态性有一定联系［1-2］。现报道1例长期使用糖皮质激素致ONFH患者，进行基因分型检测，分析基因型对SONFH的影响机制及干预措施，为临床个体化、合理用药提供参考。展开更多
Objective:In postmenopausal women,an increased leptin concentration and reduced levels of ghrelin and adiponectin were observed.The aim of this study was to evaluate the concentrations of the active form of ghrelin,to...Objective:In postmenopausal women,an increased leptin concentration and reduced levels of ghrelin and adiponectin were observed.The aim of this study was to evaluate the concentrations of the active form of ghrelin,total ghrelin,leptin receptor,lipoprotein(a)(Lp(a)),and plasminogen activator inhibitor type 1(PAI-1) in postmenopausal women who received oral or transdermal menopausal hormonal therapy(MHT).Methods:The study involved 76 healthy women:46 women aged from 44 to 58 years who received oral(26) or transdermal(20) MHT;the control group consisted of 30 women aged from 44 to 54 years who did not receive MHT.The plasma concentrations of total ghrelin,the active form of ghrelin,Lp(a),and PAI-1:Ag were measured by enzyme-linked immunosorbent assay(ELISA).The concentration of the leptin receptor was measured by enzyme immunometric assay(EIA).Results:We observed a significantly higher concentration of total ghrelin and the active form of ghrelin in women who received transdermal MHT in comparison with those who took oral MHT.We also found a significantly lower concentration of total ghrelin in women who received oral MHT compared with the control group.A higher concentration of PAI-1:Ag was found in the group of women who took transdermal MHT in comparison with those who took oral MHT and with the control group.The differences were statistically significant.Additionally,we found a significant negative correlation between the concentrations of total ghrelin and PAI-1:Ag and a positive correlation between the concentrations of total ghrelin and leptin receptor in women who received transdermal MHT.Conclusions:The study showed that women who used transdermal MHT had higher levels of total ghrelin than women who took oral MHT.This indicates a beneficial effect of the transdermal route of MHT.However,transdermal therapy was associated with adverse effects with regard to the observed higher levels of PAI-1:Ag,which in turn,can lead to a reduction in fibrinolytic activity.展开更多
基金Research Programme of the Shanghai Municipal Science and Technology Commission(No.06DZ19505)
文摘Objective:To investigate the expressions of plasminogen activator inhibitor type 1 (PAI-1), C-erbB-2, VEGF and Ki-67 by immunohistostaining and then to evaluate the prognostic value of PAI-1 in node-negative breast cancer. Methods:The study included a retrospective series of 62 female patients with axillary lymph node-negative breast cancer. Expressions of PAI-1, C-erbB-2, VEGF and Ki-67 were determined by immunohistostaining on formalin-fixed paraffin-embedded tissue sections from these patients after a median follow-up of 69 months (range 22–117 months). Correlations with well known clinicopathologic factors were assessed and multivariate survival analyses were performed. Results: High PAI-1 level was positively associated with high histologic grade of the tumors. Disease-free survival (DFS) was significantly shorter for the patients with moderate to intensive expression of PAI-1 than for those with negative (χ2 = 25.46, P < 0.001; χ2 = 23.07, P < 0.001) to mild expression (χ2 = 19.75, P < 0.001; χ2 = 17.40, P < 0.001). Although on univariate analysis of the prognostic factors, tumor size, location of primary tumor and age as well as expressions of PAI-1, VEGF and Ki-67 were all significantly prognostic factors for DFS (P < 0.05), PAI-1 was the only independent prognostic factor on multivariate analysis (P<0.0001; hazard ratio [HR], 4.041; 95% confidence interval [CI], 1.928–8.468). Conclusion: These results of the current study indicate that intermediate or high expression of PAI-1 represents a strong and independent unfavorable prognostic factor for the de-velopment of recurrence or metastases in axillary node-negative breast cancer.
基金supported by the National Natural Science Foundation of China(Nos.81202882,82060670)Suzhou Science and Technology Planning Project in Jiangsu Province of China(No.SNG2021022)+1 种基金the Priority Academic Program Development of the Jiangsu Higher Education Institutes,China(PAPD)and the Project of Innovative Research Team of Yunnan Province(No.202005AE160005).
文摘In this study,37 derivatives of phorbol esters were synthesized and their anti-HIV-1 activities evaluated,building upon our previous synthesis of 51 phorbol derivatives.12-Para-electron-acceptor-trans-cinnamoyl-13-decanoyl phorbol derivatives stood out,demonstrating remarkable anti-HIV-1 activities and inhibitory effects on syncytia formation.These derivatives exhibited a higher safety index compared with the positive control drug.Among them,12-(trans-4-fluorocinnamoyl)-13-decanoyl phorbol,designated as compound 3c,exhibited the most potent anti-HIV-1 activity(EC_(50)2.9 nmol·L^(−1),CC50/EC_(50)11117.24)and significantly inhibited the formation of syncytium(EC_(50)7.0 nmol·L^(−1),CC50/EC_(50)4891.43).Moreover,compound 3c is hypothesized to act both as an HIV-1 entry inhibitor and as an HIV-1 reverse transcriptase inhibitor.Isothermal titration calorimetry and molecular docking studies indicated that compound 3c may also function as a natural activator of protein kinase C(PKC).Therefore,compound 3c emerges as a potential candidate for developing new anti-HIV drugs.
文摘随着糖皮质激素在临床的广泛应用，激素性股骨头坏死（steroid-induced osteonecrosis of the femoral head，SONFH）成为非创伤性股骨头坏死（ osteonecrosis of the femoral head，ONFH）的主要原因，约占非创伤性ONFH的2／3。长期接受糖皮质激素治疗或接受大剂量糖皮质激素冲击治疗的患者中，9％～40％可能会发生SONFH，同时伴有糖皮质激素诱导的骨质疏松。随着基因组学的发展，发现SONFH的发生与纤溶酶原激活物抑制物-1（ plasminogen activator inhibitor-1，PAI-1）和三磷酸腺苷黏合转运体B1（adenosine triphosphate binding cassette B1，ABCB1）的基因多态性有一定联系［1-2］。现报道1例长期使用糖皮质激素致ONFH患者，进行基因分型检测，分析基因型对SONFH的影响机制及干预措施，为临床个体化、合理用药提供参考。
基金Project supported by the Collegium Medicum in Bydgoszcz,Nicolaus Copernicus University in Toruń (No.73/04),Poland
文摘Objective:In postmenopausal women,an increased leptin concentration and reduced levels of ghrelin and adiponectin were observed.The aim of this study was to evaluate the concentrations of the active form of ghrelin,total ghrelin,leptin receptor,lipoprotein(a)(Lp(a)),and plasminogen activator inhibitor type 1(PAI-1) in postmenopausal women who received oral or transdermal menopausal hormonal therapy(MHT).Methods:The study involved 76 healthy women:46 women aged from 44 to 58 years who received oral(26) or transdermal(20) MHT;the control group consisted of 30 women aged from 44 to 54 years who did not receive MHT.The plasma concentrations of total ghrelin,the active form of ghrelin,Lp(a),and PAI-1:Ag were measured by enzyme-linked immunosorbent assay(ELISA).The concentration of the leptin receptor was measured by enzyme immunometric assay(EIA).Results:We observed a significantly higher concentration of total ghrelin and the active form of ghrelin in women who received transdermal MHT in comparison with those who took oral MHT.We also found a significantly lower concentration of total ghrelin in women who received oral MHT compared with the control group.A higher concentration of PAI-1:Ag was found in the group of women who took transdermal MHT in comparison with those who took oral MHT and with the control group.The differences were statistically significant.Additionally,we found a significant negative correlation between the concentrations of total ghrelin and PAI-1:Ag and a positive correlation between the concentrations of total ghrelin and leptin receptor in women who received transdermal MHT.Conclusions:The study showed that women who used transdermal MHT had higher levels of total ghrelin than women who took oral MHT.This indicates a beneficial effect of the transdermal route of MHT.However,transdermal therapy was associated with adverse effects with regard to the observed higher levels of PAI-1:Ag,which in turn,can lead to a reduction in fibrinolytic activity.
