Objectives:Cisplatin(CDDP)is a widely used and effective basic chemotherapeutic drug for the treatment of a variety of tumors,including ovarian cancer.However,adverse side effects and acquired drug resistance are obse...Objectives:Cisplatin(CDDP)is a widely used and effective basic chemotherapeutic drug for the treatment of a variety of tumors,including ovarian cancer.However,adverse side effects and acquired drug resistance are observed in the clinical application of CDDP.Identifying a mode of administration that can alleviate side effects and reduce drug resistance has become a promising strategy to solve this problem.Methods:In this study,3 D printing technology was used to prepare a CDDP-poly(lactic-co-glycolic acid)(CDDP-PLGA)polymer compound stent,and its physicochemical properties and cytotoxicity were evaluated both in vitro and in vivo.Results:The CDDP-PLGA stent had a significant effect on cell proliferation and apoptosis and clearly decreased the size of subcutaneous tumors in nude mice,whereas the systemic side effects were mild compared with those of intraperitoneal CDDP injection.Compared with the control group,CDDP-PLGA significantly increased the mRNA and protein levels of p-glycoprotein(P<0.01;P<0.01)and decreased vascular endothelial growth factor mRNA(P<0.05)and protein levels(P<0.01),however,CDDP-PLGA significantly decreased the mR NA and protein levels of p-glycoprotein(P<0.01;P<0.01)and vascular endothelial growth factor(P<0.01;P<0.01),which are associated with chemoresistance,in subcutaneous tumor tissue.Immunohistochemistry assay results revealed that,in the CDDP-PLGA group,the staining of the proliferation-related genes Ki67 and PCNA were lightly,and the apoptosis-related gene caspase-3 stained deeply.Conclusions:PLGA biomaterials loaded with CDDP,as compared with the same amount of free CDDP,showed good efficacy in terms of cytotoxicity,as evidenced by changes in apoptosis.Continuous local CDDP release can decrease the systemic side effects of this drug and the occurrence of drug resistance and angiogenesis,and improve the therapeutic effect.This new approach may be an effective strategy for the local treatment of epithelial ovarian cancer.展开更多
Surface modification of microporous bone scaffolds using nanoparticles has been broadly studied in bone tissue engineering.Aiming at improving vascularized bone regeneration(VBR),zeolitic imidazolate framework-8(ZIF-8...Surface modification of microporous bone scaffolds using nanoparticles has been broadly studied in bone tissue engineering.Aiming at improving vascularized bone regeneration(VBR),zeolitic imidazolate framework-8(ZIF-8)was encapsulated with dimethyloxallyl glycine(DMOG)and the drug-carrying nanoparticles(D@Z)could be uniformly coated onto the surface of the bone scaffold.The osteogenic and angiogenic actions of D@Z are closely correlated with the amount of slowly released DMOG,and in general,exhibited a favorable association.Then,the D7.5@Z group,which showed the greatest capacity to induce in vitro osteogenesis-angiogenesis coupling,was utilized for surface modification of the bone scaffold.Biological processes including phosphate-containing compound metabolic process,cell differentiation,cell proliferation and cell motility might contribute to enhanced ability to induce VBR by the coated scaffold and signaling pathways such as Rap1,Ras,phosphatidylinositol 3-kinase/protein kinase B(PI3K-AKT)and vascular endothelial growth factor(VEGF)signaling pathways participated in these processes.Finally,as depicted by in vitro real time-polymerase chain reaction(RT-PCR),Western blot(WB)and in vivo cranial bone defect model,the microporous scaffold coated with nano-D7.5@Z greatly promoted VBR.To conclude,nano-D@Z has significant promise for practical application in modification of microporous bone scaffolds to enhance VBR,and DMOG loading quantity has a beneficial influence on D@Z to improve osteogenesis-angiogenesis coupling.展开更多
Background Polymer coating on coronary stents induces vascular inflammatory response, reduces re-endothelialization, and affects long-term outcome after percutaneous coronary intervention （PCI）. The SERY-1 registry ...Background Polymer coating on coronary stents induces vascular inflammatory response, reduces re-endothelialization, and affects long-term outcome after percutaneous coronary intervention （PCI）. The SERY-1 registry aimed to determine whether a novel polymer-free paclitaxel-eluting microporous Yinyi stent could improve 1-year outcome after index procedure in real-world clinical practice. Methods Clinical and angiographic data and follow-up outcome were collected in 1045 patients who underwent PCI with implantation of 〉1 Yinyi stents between June 2008 and August 2009 at 27 medical centers. The primary endpoint was the cumulative rate of composite major adverse cardiac events （MACE） and the secondary endpoint was the incidence of stent thrombosis at 1 year. Results Overall, 1376 lesions were treated successfully with 1713 Yinyi stents, and 1019 （98.7%） patients received dual antiplatelet therapy for at least 12 months. During 1-year follow-up, 8 patients （0.78%） had cardiac death, 6 （0.58%） suffered non-fatal myocardial infarction, and 46 （4.46%） underwent repeat PCI due to recurrence of angina, resulting in 1-year MACE-free survival of 94.09%. Stent thrombosis occurred in 10 （0.97%） patients, and the rate of Academic Research Consortium （ARC） definite or probable stent thrombosis was 0.78%. Conclusions Polymer-free paclitaxel-eluting microporous Yinyi stent is effective and safe for interventional treatment of coronary artery disease in real-world clinical practice, without recourse to carrier polymer. Potential long-term clinical advantages of this stent deserve further investigation.展开更多
基金funded by the Hubei Province Health and Family Planning Scientific Research Project(Grant No.WJ2019M179)partially supported by the National Natural Science Foundation of China(Grant No.81860276)。
文摘Objectives:Cisplatin(CDDP)is a widely used and effective basic chemotherapeutic drug for the treatment of a variety of tumors,including ovarian cancer.However,adverse side effects and acquired drug resistance are observed in the clinical application of CDDP.Identifying a mode of administration that can alleviate side effects and reduce drug resistance has become a promising strategy to solve this problem.Methods:In this study,3 D printing technology was used to prepare a CDDP-poly(lactic-co-glycolic acid)(CDDP-PLGA)polymer compound stent,and its physicochemical properties and cytotoxicity were evaluated both in vitro and in vivo.Results:The CDDP-PLGA stent had a significant effect on cell proliferation and apoptosis and clearly decreased the size of subcutaneous tumors in nude mice,whereas the systemic side effects were mild compared with those of intraperitoneal CDDP injection.Compared with the control group,CDDP-PLGA significantly increased the mRNA and protein levels of p-glycoprotein(P<0.01;P<0.01)and decreased vascular endothelial growth factor mRNA(P<0.05)and protein levels(P<0.01),however,CDDP-PLGA significantly decreased the mR NA and protein levels of p-glycoprotein(P<0.01;P<0.01)and vascular endothelial growth factor(P<0.01;P<0.01),which are associated with chemoresistance,in subcutaneous tumor tissue.Immunohistochemistry assay results revealed that,in the CDDP-PLGA group,the staining of the proliferation-related genes Ki67 and PCNA were lightly,and the apoptosis-related gene caspase-3 stained deeply.Conclusions:PLGA biomaterials loaded with CDDP,as compared with the same amount of free CDDP,showed good efficacy in terms of cytotoxicity,as evidenced by changes in apoptosis.Continuous local CDDP release can decrease the systemic side effects of this drug and the occurrence of drug resistance and angiogenesis,and improve the therapeutic effect.This new approach may be an effective strategy for the local treatment of epithelial ovarian cancer.
基金supported by the National Natural Science Foundation of China(Nos.82201128,82271034)Special Funding for Post-doctoral Research Projects in Sichuan Province(No.TB2022045)+2 种基金Sichuan Province Science and Technology Plan Projects(No.23NSFSC1723)China Postdoctoral Science Foundation(No.2022M722250)Research and Development Program(West China Hospital of Stomatology Sichuan University)(Nos.RD-02–2022012,RD-03–202107)。
文摘Surface modification of microporous bone scaffolds using nanoparticles has been broadly studied in bone tissue engineering.Aiming at improving vascularized bone regeneration(VBR),zeolitic imidazolate framework-8(ZIF-8)was encapsulated with dimethyloxallyl glycine(DMOG)and the drug-carrying nanoparticles(D@Z)could be uniformly coated onto the surface of the bone scaffold.The osteogenic and angiogenic actions of D@Z are closely correlated with the amount of slowly released DMOG,and in general,exhibited a favorable association.Then,the D7.5@Z group,which showed the greatest capacity to induce in vitro osteogenesis-angiogenesis coupling,was utilized for surface modification of the bone scaffold.Biological processes including phosphate-containing compound metabolic process,cell differentiation,cell proliferation and cell motility might contribute to enhanced ability to induce VBR by the coated scaffold and signaling pathways such as Rap1,Ras,phosphatidylinositol 3-kinase/protein kinase B(PI3K-AKT)and vascular endothelial growth factor(VEGF)signaling pathways participated in these processes.Finally,as depicted by in vitro real time-polymerase chain reaction(RT-PCR),Western blot(WB)and in vivo cranial bone defect model,the microporous scaffold coated with nano-D7.5@Z greatly promoted VBR.To conclude,nano-D@Z has significant promise for practical application in modification of microporous bone scaffolds to enhance VBR,and DMOG loading quantity has a beneficial influence on D@Z to improve osteogenesis-angiogenesis coupling.
文摘Background Polymer coating on coronary stents induces vascular inflammatory response, reduces re-endothelialization, and affects long-term outcome after percutaneous coronary intervention （PCI）. The SERY-1 registry aimed to determine whether a novel polymer-free paclitaxel-eluting microporous Yinyi stent could improve 1-year outcome after index procedure in real-world clinical practice. Methods Clinical and angiographic data and follow-up outcome were collected in 1045 patients who underwent PCI with implantation of 〉1 Yinyi stents between June 2008 and August 2009 at 27 medical centers. The primary endpoint was the cumulative rate of composite major adverse cardiac events （MACE） and the secondary endpoint was the incidence of stent thrombosis at 1 year. Results Overall, 1376 lesions were treated successfully with 1713 Yinyi stents, and 1019 （98.7%） patients received dual antiplatelet therapy for at least 12 months. During 1-year follow-up, 8 patients （0.78%） had cardiac death, 6 （0.58%） suffered non-fatal myocardial infarction, and 46 （4.46%） underwent repeat PCI due to recurrence of angina, resulting in 1-year MACE-free survival of 94.09%. Stent thrombosis occurred in 10 （0.97%） patients, and the rate of Academic Research Consortium （ARC） definite or probable stent thrombosis was 0.78%. Conclusions Polymer-free paclitaxel-eluting microporous Yinyi stent is effective and safe for interventional treatment of coronary artery disease in real-world clinical practice, without recourse to carrier polymer. Potential long-term clinical advantages of this stent deserve further investigation.
