Exclusion and inflammation in the clinic are observe d for various reas ons including material che- mical composition, physical properties as well a s macr o- and micro-structure of the implants, surface condition of ...Exclusion and inflammation in the clinic are observe d for various reas ons including material che- mical composition, physical properties as well a s macr o- and micro-structure of the implants, surface condition of the implants, and also patient dependent factors. Cytotoxicity expression of cells is a central issue i n current biocompatibility to screen the potential implant materials and drugs. This study was aimed at investigation reaction between the potential implant mat erials and surround tissue. Cytotoxicity of human and rat osteoblast in the mate rial extracts was determinated by testing standards such as GHS assay, MTT assay , alkaline phosphatase activity assay, LDH assay, and Lowry assay. Research resu lts demonstrated that compared with the control condition polystyrene culture pl a te both human and rat osteoblast cells have normal phenotypic expression in hydr oxyapatite extract, and this expression was statistically restricted in hydroxya patite-spinel extract. How- ever, this restrict, e.g. cytotoxicity could be partially eliminated by immersion treatment of the materials in culture medium.展开更多
Mg-6%Zn-10%β-Ca3(PO4)2 composite was prepared through powder metallurgy methods with different chitosan coatings on its surface. The properties of the chitosan coatings on the surface of Mg-6%Zn-10%β-Ca3(PO4)2 compo...Mg-6%Zn-10%β-Ca3(PO4)2 composite was prepared through powder metallurgy methods with different chitosan coatings on its surface. The properties of the chitosan coatings on the surface of Mg-6%Zn-10%β-Ca3(PO4)2 composite, such as the adhesion ability, the corrosion behavior and the cytotoxicity properties, were investigated, and the microstructure of the chitosan coating was observed by scanning electron microscope(SEM). The results show that chitosan coating improves the corrosion resistance of the magnesium composite specimens significantly. Mg-6%Zn-10%β-Ca3(PO4)2 composite specimens exhibit good corrosion resistance and low p H values in simulated body fluid(SBF) at 37 °C in the immersion test with 7-layer chitosan coating whose relative molecular mass is 30×104 Da. The cytotoxicity tests indicate that Mg-6%Zn-10%β-Ca3(PO4)2 with chitosan coating is nontoxic with a cytotoxicity grade of zero against L-929 cells, which is better than that of uncoated composites.展开更多
The elimination of the tumor is closely relatedwith the sensitivity of tumor cells to the cytotoxicityof immune effector cells. We supposed that cytokinegenetransfection may increase the cytotoxicitysusceptibility of ...The elimination of the tumor is closely relatedwith the sensitivity of tumor cells to the cytotoxicityof immune effector cells. We supposed that cytokinegenetransfection may increase the cytotoxicitysusceptibility of tumor cells to effector cells, and as aconsequence, the tumorigenicity decreased. Beforekilling tumor cells, effector cells required first torecognize non-specific surface adhesion molecules展开更多
Since the beginning of gene therapy, most of genetransfection were focused on the tumor cells or effectorcells. We selected macrophages as the target cells of genetransfection because they are not only antitumor effec...Since the beginning of gene therapy, most of genetransfection were focused on the tumor cells or effectorcells. We selected macrophages as the target cells of genetransfection because they are not only antitumor effectorcells but also antigen-presenting cells.They act as abridge connecting tumor cells with immune effector cells.Two cytokines we chosen are closely linkcd with thefunctions of macrophage. IFN-γis a principle factor toactivate macrophages and it incrcases MHC expression ofthem which can improve their antigen presenting ability.M-CSF is an important cytokine to keep theproliferation, differentiation and maturation ofmacrophage progenitor cells. In this study, we used展开更多
In this study A549 cell viability, extracellular activities of lactate dehydrogenase (LDH), tumor necrosis factor (TNF)–α and interleukin (IL)-6 levels were investgated after incubation with quartz (KWC-Q4 and KWC-Q...In this study A549 cell viability, extracellular activities of lactate dehydrogenase (LDH), tumor necrosis factor (TNF)–α and interleukin (IL)-6 levels were investgated after incubation with quartz (KWC-Q4 and KWC-Q3), Nano-SiO2, and KWC-M, the micronucleaus test and comet assay was carried out to evaluate the genotoxicity. The results showed that, there were significant difference in the cell death rate and extracellular LDH activity compared with the control group, and appeared a good linear relationship in certain concentration range. All mineral particle tested can induce the increase of TNF-α after incubation with mineral powders at 200 μg/mL for 3h merely, and significant increase of IL-6 for 24h, the results indicated the inflammatory reaction can be triggered by the exposure of KWC-Q4, KWC-Q3, Nano-SiO2, and KWC-M. The micronucleus test result showed the MNF (Micronucleus frequency) listed as Nano-SiO2>KWC-Q3>KWC-Q4. There is no significant increase of KWC-M compared with the control group, maybe resulted from its high cell death rate at low concentration. The comet assay confirmed the genotoxicity of all samples tested, the DNA damage: KWC-M > Nano-SiO2 > KWC-Q4 > KWC-Q3.展开更多
Large scaled uniform and size-controllable magnetic submicroparticles(MSPs) were synthesized via solvothermal method with ferric chloride as iron source and sodium acetate as trapping agent. The influence of Fe^(3+) a...Large scaled uniform and size-controllable magnetic submicroparticles(MSPs) were synthesized via solvothermal method with ferric chloride as iron source and sodium acetate as trapping agent. The influence of Fe^(3+) and Na Ac contents on the size distribution of MSPs was investigated. The structural and morphological properties of the synthesized particles were studied by scanning electron microscopy(SEM), X-ray power diffraction(XRD) and vibrating sample magnetometer(VSM). The well-dispersed MSPs with size of 100-1000 nm were obtained by simply adjusting the contents of Fe^(3+) and NaA c. In addition, the hemolysis and cytotoxicity of Fe_3O_4 MSPs, and their ability to case arrest in cell life-cycles were studied. The results indicate that larger size could lead to lower hemolysis. From MTT(3-(4,5-dimethylthuazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, the interactions between MSPs and adhesive mouse fibroblast cell line(L929) were probed. Larger size of Fe_3O_4 MSPs demonstrates lower cell viability following an exposure to the cells.展开更多
Oncolysate, a debris of tumor cells, has been provento be effective in tumor active immunotherapy, it wasreported that the vaccinia virus, especially recombinantvaccinia viruses encoding human IL-2 (rVV-IL-2 ),enhance...Oncolysate, a debris of tumor cells, has been provento be effective in tumor active immunotherapy, it wasreported that the vaccinia virus, especially recombinantvaccinia viruses encoding human IL-2 (rVV-IL-2 ),enhanced the immunogenicity of transfected tumor cells.In this experiment, the murine melanoma cell B16-F10oncolysates trans fected by rVV-IL-2 (IL-2VBO) wereused as vaccine. The IL-2VBO or TK-VBO was preparedby incubating B16-F10 cells with rVV-IL-2 or rVV-TK展开更多
Effects of fibroblast-mediated IL-2 and IL-3 genetherapy on recovery of bone marrow depression in tumor-bearing mice treated with cyclophosphamide (300 mg/kg) and syngeneic BMT were investigated in the presentreport. ...Effects of fibroblast-mediated IL-2 and IL-3 genetherapy on recovery of bone marrow depression in tumor-bearing mice treated with cyclophosphamide (300 mg/kg) and syngeneic BMT were investigated in the presentreport. BALB/c mice were inoculated with J558Lplasmacytoma cells s. c. and 3 days later IL-2 secretingNIH3T3-IL-2, IL-3 secreting NIH3T3-IL-3 fibroblastcells were implanted into the tumor-bearing mice展开更多
It’s well known that interleukin-2 (IL-2) plays animportant role in eliciting antitumor immunityparticularly mediated by T cells. In addition, theexpression of MHC can be enhanced by IL-2 genetransfection in tumor ce...It’s well known that interleukin-2 (IL-2) plays animportant role in eliciting antitumor immunityparticularly mediated by T cells. In addition, theexpression of MHC can be enhanced by IL-2 genetransfection in tumor cells. Recent studies have indicatedthat at least two signals are required for the activation ofnaive T cells by antigen-bearing target cells: an antigen-sopific signal and a crystimulatory signal. B7-l is展开更多
Chemotherapy is one of the curative treatmentmodality for several types of tumors. However, thedosage of antitumor drugs was limited by cytotoxicityof drugs to normal tissues, especially for bone marrow(myelosuppressi...Chemotherapy is one of the curative treatmentmodality for several types of tumors. However, thedosage of antitumor drugs was limited by cytotoxicityof drugs to normal tissues, especially for bone marrow(myelosuppression). Drug resistantce gene (hMDRI,hDHFR etc.) is expressed in many normal tissues. Itsover-expression in tumor cells give rise to the tumorresistant to many drugs. But, if we transfer the drugresistance gene into the normal hematopoietic stemcell (HSC), the expression of the foreign gene展开更多
OBJECTIVE Cytochrome P450(CYP)2J2 is highly expressed in many kinds of human tumors and promotes tumor cell growth via regulating the metabolism of arachidonic acids.The purposes of this study were toidentify the new ...OBJECTIVE Cytochrome P450(CYP)2J2 is highly expressed in many kinds of human tumors and promotes tumor cell growth via regulating the metabolism of arachidonic acids.The purposes of this study were toidentify the new inhibitor of CYP2J2 from natural compounds and evaluate its potential to inhibit hepatoma carcinoma cells.METHODS Total fifty natural products were screened for the inhibitory potency against the activity of CYP2J2-mediated astemizole O-demethylation via LCMS/MS analysis.Enzyme kinetic and molecular docking studies were also carried out.RESULTS Our data found that plumbagin potently inhibited CYP2J2 with IC50value at 3.42,3.37 and 1.17μmol·L-1in rat liver microsomes,human liver microsomes(HLMs)and recombinant CYP2J2(rC YP2J2),respectively.Further enzyme kinetic studies showed that plumbagin was a mixed-type inhibitor of CYP2J2 in HLMs and r CYP2J2 with Kivalues of 1.88and 0.92μmol·L-1,respectively.Docking data presented that plumbagin interacted with CYP2J2 mainly through GLU222 and ALA223,which were crucial residues for substrates binding.At the same time,plumbagin showed cytotoxicity effects on hepatic carcinoma cell lines,such as HepG 2 and SMMC-7721,with IC50values at 11.55±1.06and(13.15±1.11)μmol·L-1,respectively.CONCLUSION These results indicated that plumbagin was a potent CYP2J2 inhibitor and potential anticancer agent.Further studies are needed to cover the mechanism of its antitumor activity.展开更多
Viral-mediated gene transfer of thymidine kinase ofherpes simplex virus (HSV-tk) has been used to confercytotoxic sensitivity to ganciclovir (GCV) in a variety oftnmor cells. HSV-tk converts GCV into a phosphorylatedc...Viral-mediated gene transfer of thymidine kinase ofherpes simplex virus (HSV-tk) has been used to confercytotoxic sensitivity to ganciclovir (GCV) in a variety oftnmor cells. HSV-tk converts GCV into a phosphorylatedcompound which is toxic for dividing cells by blockingDNA synthesis. Our previous study has shown展开更多
Utilization of gene therapy approaches for cancertreatment requires either that the transferred genegains access to the great majority of the tumor cells orthat gene transfer results in a cytotoxic effect that willkil...Utilization of gene therapy approaches for cancertreatment requires either that the transferred genegains access to the great majority of the tumor cells orthat gene transfer results in a cytotoxic effect that willkill a large number of tumor cells that do not directlyreceive the gene of interest. The latter effect can beachieved by the transfer into tumors of展开更多
Anti-Fas or Fas ligand can induce apoptosis whenthey bind Fas antigen on cell surfaces, and have potentialtherapeutic uses. But the disadvantage is obvious asnormal cells can also be killed. In this paper, weconstruct...Anti-Fas or Fas ligand can induce apoptosis whenthey bind Fas antigen on cell surfaces, and have potentialtherapeutic uses. But the disadvantage is obvious asnormal cells can also be killed. In this paper, weconstructed a fusion protein between the transmembraneand cytoplasmic domains of hfas and the HBD (hormonebinding domain) of hER (referred to as MfasER).Glioma cells transfeced with MfasER could be indued展开更多
Tumor necrosis factor α (TNFα) and interleukin 2(IL-2) are cytokines that possess potent antitumor andimmunomodulatory activity such as enhancing monocyte-macrophage and neutrophil cytotoxic activities,increasing T ...Tumor necrosis factor α (TNFα) and interleukin 2(IL-2) are cytokines that possess potent antitumor andimmunomodulatory activity such as enhancing monocyte-macrophage and neutrophil cytotoxic activities,increasing T cell proliferation and IL-2 receptorexpression and augmenting cytotoxicity of cytotoxic Tlymphocyte. To investigate the therapeutic effect of thedirect cytokine gene transfer, recombinant展开更多
The essence of gene therapy is to placefunctioning genes into a patient’s cells for therapeuticpurposes. Gene therapy may be employed to ①enhance anti-tumor immune responses; ②
Recombinant vaccinia virus has many advantagesover more restricted vectors like retrovirus andadenovirus. The proven safety of vaccinia virus, which isrestricted to local and transitory infection, favors clinicalappli...Recombinant vaccinia virus has many advantagesover more restricted vectors like retrovirus andadenovirus. The proven safety of vaccinia virus, which isrestricted to local and transitory infection, favors clinicalapplication of vaccinia virus to deliver cytokines locally.展开更多
文摘Exclusion and inflammation in the clinic are observe d for various reas ons including material che- mical composition, physical properties as well a s macr o- and micro-structure of the implants, surface condition of the implants, and also patient dependent factors. Cytotoxicity expression of cells is a central issue i n current biocompatibility to screen the potential implant materials and drugs. This study was aimed at investigation reaction between the potential implant mat erials and surround tissue. Cytotoxicity of human and rat osteoblast in the mate rial extracts was determinated by testing standards such as GHS assay, MTT assay , alkaline phosphatase activity assay, LDH assay, and Lowry assay. Research resu lts demonstrated that compared with the control condition polystyrene culture pl a te both human and rat osteoblast cells have normal phenotypic expression in hydr oxyapatite extract, and this expression was statistically restricted in hydroxya patite-spinel extract. How- ever, this restrict, e.g. cytotoxicity could be partially eliminated by immersion treatment of the materials in culture medium.
基金Project(2012zzts068) supported by the Fundamental Research Funds for the Central Universities of Central South University,ChinaProject(2010fj3091) supported by the Open Funding of State Key Laboratory of Powder Metallurgy and Science&Technology Foundation,China
文摘Mg-6%Zn-10%β-Ca3(PO4)2 composite was prepared through powder metallurgy methods with different chitosan coatings on its surface. The properties of the chitosan coatings on the surface of Mg-6%Zn-10%β-Ca3(PO4)2 composite, such as the adhesion ability, the corrosion behavior and the cytotoxicity properties, were investigated, and the microstructure of the chitosan coating was observed by scanning electron microscope(SEM). The results show that chitosan coating improves the corrosion resistance of the magnesium composite specimens significantly. Mg-6%Zn-10%β-Ca3(PO4)2 composite specimens exhibit good corrosion resistance and low p H values in simulated body fluid(SBF) at 37 °C in the immersion test with 7-layer chitosan coating whose relative molecular mass is 30×104 Da. The cytotoxicity tests indicate that Mg-6%Zn-10%β-Ca3(PO4)2 with chitosan coating is nontoxic with a cytotoxicity grade of zero against L-929 cells, which is better than that of uncoated composites.
文摘The elimination of the tumor is closely relatedwith the sensitivity of tumor cells to the cytotoxicityof immune effector cells. We supposed that cytokinegenetransfection may increase the cytotoxicitysusceptibility of tumor cells to effector cells, and as aconsequence, the tumorigenicity decreased. Beforekilling tumor cells, effector cells required first torecognize non-specific surface adhesion molecules
文摘Since the beginning of gene therapy, most of genetransfection were focused on the tumor cells or effectorcells. We selected macrophages as the target cells of genetransfection because they are not only antitumor effectorcells but also antigen-presenting cells.They act as abridge connecting tumor cells with immune effector cells.Two cytokines we chosen are closely linkcd with thefunctions of macrophage. IFN-γis a principle factor toactivate macrophages and it incrcases MHC expression ofthem which can improve their antigen presenting ability.M-CSF is an important cytokine to keep theproliferation, differentiation and maturation ofmacrophage progenitor cells. In this study, we used
文摘In this study A549 cell viability, extracellular activities of lactate dehydrogenase (LDH), tumor necrosis factor (TNF)–α and interleukin (IL)-6 levels were investgated after incubation with quartz (KWC-Q4 and KWC-Q3), Nano-SiO2, and KWC-M, the micronucleaus test and comet assay was carried out to evaluate the genotoxicity. The results showed that, there were significant difference in the cell death rate and extracellular LDH activity compared with the control group, and appeared a good linear relationship in certain concentration range. All mineral particle tested can induce the increase of TNF-α after incubation with mineral powders at 200 μg/mL for 3h merely, and significant increase of IL-6 for 24h, the results indicated the inflammatory reaction can be triggered by the exposure of KWC-Q4, KWC-Q3, Nano-SiO2, and KWC-M. The micronucleus test result showed the MNF (Micronucleus frequency) listed as Nano-SiO2>KWC-Q3>KWC-Q4. There is no significant increase of KWC-M compared with the control group, maybe resulted from its high cell death rate at low concentration. The comet assay confirmed the genotoxicity of all samples tested, the DNA damage: KWC-M > Nano-SiO2 > KWC-Q4 > KWC-Q3.
基金Project(2013DFA5129)supported by the International Science and Technology Cooperation Program of China
文摘Large scaled uniform and size-controllable magnetic submicroparticles(MSPs) were synthesized via solvothermal method with ferric chloride as iron source and sodium acetate as trapping agent. The influence of Fe^(3+) and Na Ac contents on the size distribution of MSPs was investigated. The structural and morphological properties of the synthesized particles were studied by scanning electron microscopy(SEM), X-ray power diffraction(XRD) and vibrating sample magnetometer(VSM). The well-dispersed MSPs with size of 100-1000 nm were obtained by simply adjusting the contents of Fe^(3+) and NaA c. In addition, the hemolysis and cytotoxicity of Fe_3O_4 MSPs, and their ability to case arrest in cell life-cycles were studied. The results indicate that larger size could lead to lower hemolysis. From MTT(3-(4,5-dimethylthuazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, the interactions between MSPs and adhesive mouse fibroblast cell line(L929) were probed. Larger size of Fe_3O_4 MSPs demonstrates lower cell viability following an exposure to the cells.
文摘Oncolysate, a debris of tumor cells, has been provento be effective in tumor active immunotherapy, it wasreported that the vaccinia virus, especially recombinantvaccinia viruses encoding human IL-2 (rVV-IL-2 ),enhanced the immunogenicity of transfected tumor cells.In this experiment, the murine melanoma cell B16-F10oncolysates trans fected by rVV-IL-2 (IL-2VBO) wereused as vaccine. The IL-2VBO or TK-VBO was preparedby incubating B16-F10 cells with rVV-IL-2 or rVV-TK
文摘The moditication of tumor cells or effcor cellsusing cytokine genes as a strategy to enhance hostantitumor immunity has been studied intensively over
文摘Effects of fibroblast-mediated IL-2 and IL-3 genetherapy on recovery of bone marrow depression in tumor-bearing mice treated with cyclophosphamide (300 mg/kg) and syngeneic BMT were investigated in the presentreport. BALB/c mice were inoculated with J558Lplasmacytoma cells s. c. and 3 days later IL-2 secretingNIH3T3-IL-2, IL-3 secreting NIH3T3-IL-3 fibroblastcells were implanted into the tumor-bearing mice
文摘It’s well known that interleukin-2 (IL-2) plays animportant role in eliciting antitumor immunityparticularly mediated by T cells. In addition, theexpression of MHC can be enhanced by IL-2 genetransfection in tumor cells. Recent studies have indicatedthat at least two signals are required for the activation ofnaive T cells by antigen-bearing target cells: an antigen-sopific signal and a crystimulatory signal. B7-l is
文摘Chemotherapy is one of the curative treatmentmodality for several types of tumors. However, thedosage of antitumor drugs was limited by cytotoxicityof drugs to normal tissues, especially for bone marrow(myelosuppression). Drug resistantce gene (hMDRI,hDHFR etc.) is expressed in many normal tissues. Itsover-expression in tumor cells give rise to the tumorresistant to many drugs. But, if we transfer the drugresistance gene into the normal hematopoietic stemcell (HSC), the expression of the foreign gene
基金The project supported by National Natural Science Foundation of China(81301908)the Science and Technology Commission of Shanghai Municipality(15140904700,13ZR1412600 and 14DZ2270100)
文摘OBJECTIVE Cytochrome P450(CYP)2J2 is highly expressed in many kinds of human tumors and promotes tumor cell growth via regulating the metabolism of arachidonic acids.The purposes of this study were toidentify the new inhibitor of CYP2J2 from natural compounds and evaluate its potential to inhibit hepatoma carcinoma cells.METHODS Total fifty natural products were screened for the inhibitory potency against the activity of CYP2J2-mediated astemizole O-demethylation via LCMS/MS analysis.Enzyme kinetic and molecular docking studies were also carried out.RESULTS Our data found that plumbagin potently inhibited CYP2J2 with IC50value at 3.42,3.37 and 1.17μmol·L-1in rat liver microsomes,human liver microsomes(HLMs)and recombinant CYP2J2(rC YP2J2),respectively.Further enzyme kinetic studies showed that plumbagin was a mixed-type inhibitor of CYP2J2 in HLMs and r CYP2J2 with Kivalues of 1.88and 0.92μmol·L-1,respectively.Docking data presented that plumbagin interacted with CYP2J2 mainly through GLU222 and ALA223,which were crucial residues for substrates binding.At the same time,plumbagin showed cytotoxicity effects on hepatic carcinoma cell lines,such as HepG 2 and SMMC-7721,with IC50values at 11.55±1.06and(13.15±1.11)μmol·L-1,respectively.CONCLUSION These results indicated that plumbagin was a potent CYP2J2 inhibitor and potential anticancer agent.Further studies are needed to cover the mechanism of its antitumor activity.
文摘Viral-mediated gene transfer of thymidine kinase ofherpes simplex virus (HSV-tk) has been used to confercytotoxic sensitivity to ganciclovir (GCV) in a variety oftnmor cells. HSV-tk converts GCV into a phosphorylatedcompound which is toxic for dividing cells by blockingDNA synthesis. Our previous study has shown
文摘Utilization of gene therapy approaches for cancertreatment requires either that the transferred genegains access to the great majority of the tumor cells orthat gene transfer results in a cytotoxic effect that willkill a large number of tumor cells that do not directlyreceive the gene of interest. The latter effect can beachieved by the transfer into tumors of
文摘Anti-Fas or Fas ligand can induce apoptosis whenthey bind Fas antigen on cell surfaces, and have potentialtherapeutic uses. But the disadvantage is obvious asnormal cells can also be killed. In this paper, weconstructed a fusion protein between the transmembraneand cytoplasmic domains of hfas and the HBD (hormonebinding domain) of hER (referred to as MfasER).Glioma cells transfeced with MfasER could be indued
文摘Tumor necrosis factor α (TNFα) and interleukin 2(IL-2) are cytokines that possess potent antitumor andimmunomodulatory activity such as enhancing monocyte-macrophage and neutrophil cytotoxic activities,increasing T cell proliferation and IL-2 receptorexpression and augmenting cytotoxicity of cytotoxic Tlymphocyte. To investigate the therapeutic effect of thedirect cytokine gene transfer, recombinant
文摘The essence of gene therapy is to placefunctioning genes into a patient’s cells for therapeuticpurposes. Gene therapy may be employed to ①enhance anti-tumor immune responses; ②
文摘Recombinant vaccinia virus has many advantagesover more restricted vectors like retrovirus andadenovirus. The proven safety of vaccinia virus, which isrestricted to local and transitory infection, favors clinicalapplication of vaccinia virus to deliver cytokines locally.