目的:探讨高迁移率族蛋白-1(high mobility group box-1,HMGB-1)和hepsin在宫颈癌中的表达与侵袭性、病理学分型的关系。方法:应用免疫组化(S-P)方法检测宫颈癌组织中的hepsin及HMGB-1蛋白表达。结果:HMGB-1及hespin在宫颈癌组织、癌旁...目的:探讨高迁移率族蛋白-1(high mobility group box-1,HMGB-1)和hepsin在宫颈癌中的表达与侵袭性、病理学分型的关系。方法:应用免疫组化(S-P)方法检测宫颈癌组织中的hepsin及HMGB-1蛋白表达。结果:HMGB-1及hespin在宫颈癌组织、癌旁组织及正常宫颈组织中表达差异具有统计学意义(P<0.05)。HMGB-1表达与肿瘤分化程度、淋巴结转移及TNM分期有关(P<0.05)。hepsin表达与肿瘤分化程度、浸润深度、淋巴结转移及TNM分期有关(P<0.05);hepsin及HMGB-1存在正相关性(r=15.27,P<0.05)。结论:HEPSIN及HMGB-1的增强表达与宫颈癌侵袭性增强有密切关系,其表达可作为判断宫颈癌患者预后的指标。展开更多
Hepsin,a transmembrane serine protease abundant in renal endothelial cells,is a promising therapeutic target against several cancers,particularly prostate cancer.It is involved in the release and polymerization of uro...Hepsin,a transmembrane serine protease abundant in renal endothelial cells,is a promising therapeutic target against several cancers,particularly prostate cancer.It is involved in the release and polymerization of uromodulin in the urine,which plays a role in kidney stone formation.In this work,we design new potential hepsin inhibitors for high activity,improved specificity towards hepsin,and promising ADMET properties.The ligands were developed in silico through a novel hierarchical pipeline.This pipeline explicitly accounts for off-target binding to the related serine proteases matriptase and HGFA(human hepatocyte growth factor activator).We completed the pipeline incorporating ADMET properties of the candidate inhibitors into custom multi-objective optimization functions.The ligands designed show excellent prospects for targeting hepsin via the blood stream and the urine and thus enable key experimental studies.The computational pipeline proposed is remarkably costefficient and can be easily adapted for designing inhibitors against new drug targets.展开更多
OBJECTIVE Recent studies have shown that hepsin, a type of transmembrane serine protease, is highly upregulated in prostate cancer, but, little is known about its role in progression and invasion of this cancer. We co...OBJECTIVE Recent studies have shown that hepsin, a type of transmembrane serine protease, is highly upregulated in prostate cancer, but, little is known about its role in progression and invasion of this cancer. We constructed a hepsin-expressing plasmid and transfected it into PC-3 cells to investigate the effect of the hepsin gene on the biological behavior of the PC-3 cells. METHODS Plasmid pHepsin-IRES2 was transfected into prostate cancer PC-3 cells using Fugene6, and the cells with stable hepsin expression were screened and selected with Zeocin (600 mg/L). The hepsin mRNA level was measured by real-time PCR and the growth curve of the PC-3-transfected cells assessed using MTT and BrdU assays. A Boyden chamber was used to examine the difference in invasion and metastases between transfected and non-transfected cells. RESULTS The hepsin mRNA level in pHepsin-IRES2 transfected -PC-3 cells was significantly higher than that found in the control PC -3 cells. While the growth curve of the hepsin gene transfected PC -3 cells showed that there was no significant effect on proliferation, the invasive ability of the pHepsin-IRES2 transfected PC-3 cells, as compared with control cells, was significantly increased (P<0.05). CONCLUSION The results suggest that even though hepsin has no effect on the proliferation of prostate cancer PC-3 cells, it does promote cellular invasion and metastasis.Therefore hepsin may have a role in the development of prostate cancer.展开更多
文摘目的:探讨高迁移率族蛋白-1(high mobility group box-1,HMGB-1)和hepsin在宫颈癌中的表达与侵袭性、病理学分型的关系。方法:应用免疫组化(S-P)方法检测宫颈癌组织中的hepsin及HMGB-1蛋白表达。结果:HMGB-1及hespin在宫颈癌组织、癌旁组织及正常宫颈组织中表达差异具有统计学意义(P<0.05)。HMGB-1表达与肿瘤分化程度、淋巴结转移及TNM分期有关(P<0.05)。hepsin表达与肿瘤分化程度、浸润深度、淋巴结转移及TNM分期有关(P<0.05);hepsin及HMGB-1存在正相关性(r=15.27,P<0.05)。结论:HEPSIN及HMGB-1的增强表达与宫颈癌侵袭性增强有密切关系,其表达可作为判断宫颈癌患者预后的指标。
基金the Scottish Funding Councilthe University of Edinburgh
文摘Hepsin,a transmembrane serine protease abundant in renal endothelial cells,is a promising therapeutic target against several cancers,particularly prostate cancer.It is involved in the release and polymerization of uromodulin in the urine,which plays a role in kidney stone formation.In this work,we design new potential hepsin inhibitors for high activity,improved specificity towards hepsin,and promising ADMET properties.The ligands were developed in silico through a novel hierarchical pipeline.This pipeline explicitly accounts for off-target binding to the related serine proteases matriptase and HGFA(human hepatocyte growth factor activator).We completed the pipeline incorporating ADMET properties of the candidate inhibitors into custom multi-objective optimization functions.The ligands designed show excellent prospects for targeting hepsin via the blood stream and the urine and thus enable key experimental studies.The computational pipeline proposed is remarkably costefficient and can be easily adapted for designing inhibitors against new drug targets.
文摘OBJECTIVE Recent studies have shown that hepsin, a type of transmembrane serine protease, is highly upregulated in prostate cancer, but, little is known about its role in progression and invasion of this cancer. We constructed a hepsin-expressing plasmid and transfected it into PC-3 cells to investigate the effect of the hepsin gene on the biological behavior of the PC-3 cells. METHODS Plasmid pHepsin-IRES2 was transfected into prostate cancer PC-3 cells using Fugene6, and the cells with stable hepsin expression were screened and selected with Zeocin (600 mg/L). The hepsin mRNA level was measured by real-time PCR and the growth curve of the PC-3-transfected cells assessed using MTT and BrdU assays. A Boyden chamber was used to examine the difference in invasion and metastases between transfected and non-transfected cells. RESULTS The hepsin mRNA level in pHepsin-IRES2 transfected -PC-3 cells was significantly higher than that found in the control PC -3 cells. While the growth curve of the hepsin gene transfected PC -3 cells showed that there was no significant effect on proliferation, the invasive ability of the pHepsin-IRES2 transfected PC-3 cells, as compared with control cells, was significantly increased (P<0.05). CONCLUSION The results suggest that even though hepsin has no effect on the proliferation of prostate cancer PC-3 cells, it does promote cellular invasion and metastasis.Therefore hepsin may have a role in the development of prostate cancer.
