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
Induction of tumor-specific cellular immune responseis very important in the cancer therapy. In this study,we used tumor antigen obtained by thaw of melanomacells to pulse M-CSF or/and IFN-γ gene-modificdmacrophages ...Induction of tumor-specific cellular immune responseis very important in the cancer therapy. In this study,we used tumor antigen obtained by thaw of melanomacells to pulse M-CSF or/and IFN-γ gene-modificdmacrophages before in viro infusion. Tumor membraneantigens could be phagocytosed by macrophages inculture. Antigen processing and mcxlulation of thepresentation can be achieved before macrophageinjection. The tumor antigens will be processedintracellularly by macrophages and thereafter展开更多
Direct gene transfer into somatic tissue in vivo is adeveloping technology with potential application forcancer gene therapy. Retrovirus vector, which was aneffective vehicle, still has some disadvantages ingenerating...Direct gene transfer into somatic tissue in vivo is adeveloping technology with potential application forcancer gene therapy. Retrovirus vector, which was aneffective vehicle, still has some disadvantages ingenerating high titer recombinant vectors andmanipulating to mediate in viro gene transfer. In thispaper, recombinant vaccinia virus vector encoding展开更多
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
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
Antitumor effects of combined transfer of suicidegene and cytokine gene were investigated in this report.Adenovirus harboring E.coli. cytosine deaminase (CD)gene (Ad-CD) and murine interleukin 2 (IL-2) gene(Ad-IL-2) w...Antitumor effects of combined transfer of suicidegene and cytokine gene were investigated in this report.Adenovirus harboring E.coli. cytosine deaminase (CD)gene (Ad-CD) and murine interleukin 2 (IL-2) gene(Ad-IL-2) were used for gene transfer in vitro and invivo. C57BL/6 mice were inoculated subcutaneously withB16F10 melanoma cells and three days later treated withadenovirus injection at the site of tumor inoculation.Significant inhibition of tumor growth was achieved展开更多
Numerous animal experiments and clinical trialshave demonstrated that the effects of systemicantitumor immune responses are closely correlatedwith the infiltration of effector cells, e. g.macrophages, T cells and NK c...Numerous animal experiments and clinical trialshave demonstrated that the effects of systemicantitumor immune responses are closely correlatedwith the infiltration of effector cells, e. g.macrophages, T cells and NK cells, at the site oftumor. In previous studies, we have established theIL-2, IL-4, IL-6 gene-transfected B16F10展开更多
Macrophage inflammatory protein-l, a recentlycharacterized chemokine, consists of two chains (αand β). MIP-lα has been shown to exert strongchemotactic effect on neutrophils, monocytes and Tlymphocytes. In the pres...Macrophage inflammatory protein-l, a recentlycharacterized chemokine, consists of two chains (αand β). MIP-lα has been shown to exert strongchemotactic effect on neutrophils, monocytes and Tlymphocytes. In the present study, the B16 melanomacells were transfected with recombinant adenoviruscontaining MIP-lα gene. The biological characteri-zation of the MIP-1α gene transfected B16 melanomacells was investigated. The level of MIP-1α in thesupernatant of gene-transfected melanoma cells was368±24 ng/ml/10~6/24hr.. By using Boyden chambersystem, this supernatant showed strong chemotacticactivity for NK cells, CD4^+ T cells, CD8^+ T cells orthe freshly isolated peritoneal macrophages in vitro.Though the in vitro growth of the gene-transfected B16 melanoma cclls was not aftered, the in vivogrowth of the tumor cells subcutaneously inoculatedwas significantly inhibited. The infiltration ofinflammatory cells into the tumor mass formed bygene-transfected B16 cells was much more obviousthan that by展开更多
Recent studies suggest that MHC class Ⅱ genetransfer could stimulate protective antitumor immunity.Whether xenogeneic MHC Ⅱ transfected tumor cells havethese effect is unknown. In this study, HLA-DR3 α and βchain ...Recent studies suggest that MHC class Ⅱ genetransfer could stimulate protective antitumor immunity.Whether xenogeneic MHC Ⅱ transfected tumor cells havethese effect is unknown. In this study, HLA-DR3 α and βchain cDNA were cloned by RT-PCR from human Blymphoma Raji cell line and confirmed by DNAsequencing. The recombinant expressing vectors wereconstructed by inserting the α and β chain cDNA intoPCEP4/pLXSN vectors respectively. After transfectingby lipofectamine and selecting with G418 and Hyg, theHLA-DR3 transfected mouse melanoma B16 recombinantclones were obtained. Approximately 59% of展开更多
Signal transducers and activators of transcription-3(STAT3),a central cytoplasmic transcription factor,is frequently overexpressed and constitutively activated during malignant transformation.The overexpression of STA...Signal transducers and activators of transcription-3(STAT3),a central cytoplasmic transcription factor,is frequently overexpressed and constitutively activated during malignant transformation.The overexpression of STAT3 in melanoma cells is often observed and is suggested to be involved in tumorigenesis and development.In this study,we designed several展开更多
The murine interleukin-2 gene was introduced intomurine melanoma B16 cells by retroviral vector. AfterG418 selection, a clone stably secreting high level ofinterleukin-2 (1038IU per 10~6 cells per 24 hours) wasobtaine...The murine interleukin-2 gene was introduced intomurine melanoma B16 cells by retroviral vector. AfterG418 selection, a clone stably secreting high level ofinterleukin-2 (1038IU per 10~6 cells per 24 hours) wasobtained. The tumorigenicity of this clone decreasedsignificantly as compared with parental tumor cells andtumor cells transferred neomycin gene. There was notumor developed after injection of 5×10~5 IL2-transfectedB16 cells into C57BL/6 mice. However when the展开更多
OBJECTIVE Forsythiae Fructus(Lianqiao)is a typical heat-clearing and detoxicating traditional Chinese medicine(TCM)herb,which has been traditionally used for treating cancer according to TCM theory.However,the underly...OBJECTIVE Forsythiae Fructus(Lianqiao)is a typical heat-clearing and detoxicating traditional Chinese medicine(TCM)herb,which has been traditionally used for treating cancer according to TCM theory.However,the underlying mechanism has not been fully explained.METHODS In this study,we investigated the antitumor effect of Forsythiae Fructus aqueous extract(FAE)on B16-F10 melanoma.RESULTS FAE strongly inhibited the tumor growth and metastasis formation in B16-F10 melanoma transplanted mice.The survival time of tumor-bearing mice was also significantly prolonged by FAE.The levels of ROS,MDA,TNF-αand IL-6 decreased,while GSH increased in the FAE treatment group,indicating FAE possesses strong anti-oxidative and anti-inflammatory activity.Western blotting analysis demonstrated that antioxidant proteins Nrf2 and HO-1,tumor suppressors P53 and p-PTEN,and the MAPK pathways in tumor tissues were upregulated by FAE treatment.Serum metabolomics analysis further uncovered that 17 metabolites mostly involving in glycerophospholipid metabolism were correlated with the antitumor effect of FAE.Notably,several lysophosphatidylcholines(LysoPCs)significantly decreased in tumor model group,while FAE treatment restored the changes of these phospholipids to about normal condition.LysoPC acyltransferase 1(LPCAT1)and autotaxin(ATX)highly expressed in melanoma and markedly downregulated by FAE were believed to be responsible for this modulation.CONCLUSION FAE exhibites strong antitumor activity against B16-F10 melanoma through activating MAPKs/Nrf2/HO-1 mediated anti-oxidation and anti-inflammation and modulating glycerophospholipid metabolism via downregulating LPCAT1 and ATX.Besides,it is suggested that serum LysoPCs could be potential biomarkers for the diagnosis and prognosis of melanoma.展开更多
Aim Forsythia suspensa （Thunb.） Vahl, Lianqiao in Chinese, is one of the most fundamental herbs in traditional Chinese medicine （TCM） with heat-clearing and detoxicating properties. In this study, we aimed to stud...Aim Forsythia suspensa （Thunb.） Vahl, Lianqiao in Chinese, is one of the most fundamental herbs in traditional Chinese medicine （TCM） with heat-clearing and detoxicating properties. In this study, we aimed to study the antitumor activity of Lianqiao aqueous extract against melanoma using cancer cell line-based in vitro and mouse allografl tumor in vivo models. Furthermore, we also investigated the underlying molecular mechanisms, par- ticularly the involvement of anti-inflammation and anti-oxidation properties in its antitumor activity. Methods The proliferation of cancer cells was measured by MTT assay. The transplanted B16-F10 melanoma in C57BL/6 mice were established and used for the evaluation of in vivo antitumor effect of LQ. Tumor growth was monitored twice a week. Ki67 and CD31 were used to detect cancer cell proliferation and angiogenesis in tumor, respectively. The anti-oxidative property of LQ was determined by measuring the levels of ROS, MDA and GSH. The anti-inflamma- tory effect of LQ was evaluated by measuring TNF-α and IL-6 using ELISA kits. Other protein expression was deter- mined by Western Blot. Results LQ strongly inhibited the growth of B16-F10 cells in vitro and the tumor growth in vivo. The survival time of tumor-bearing mice was significantly prolonged by LQ. LQ inhibited cancer cell prolif- eration and angiogenesis in tumor as evidenced by decreased expressions of Ki67 and CD31. Levels of ROS, MDA TNF-α and IL-6 decreased, while GSH increased in LQ treatment group, indicating a strong anti-oxidative and an- ti-inflammatory activity of LQ. The expression of antioxidant proteins Nff-2 and HO-1, tumor suppressors P53 and p-PTEN, and the MAPK pathways in tumor tissues were upregulated by LQ treatment. Conclusions LQ exhibited strong antitumor activity against B16-F10 murine melanoma both in vitro and in vivo. The antitumor effect of LQ in- volved the decreased oxidative stress and inflammation in tumor, which is closely related to the heat-clearing and detoxicating properties of LQ.展开更多
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Induction of tumor-specific cellular immune responseis very important in the cancer therapy. In this study,we used tumor antigen obtained by thaw of melanomacells to pulse M-CSF or/and IFN-γ gene-modificdmacrophages before in viro infusion. Tumor membraneantigens could be phagocytosed by macrophages inculture. Antigen processing and mcxlulation of thepresentation can be achieved before macrophageinjection. The tumor antigens will be processedintracellularly by macrophages and thereafter
文摘Direct gene transfer into somatic tissue in vivo is adeveloping technology with potential application forcancer gene therapy. Retrovirus vector, which was aneffective vehicle, still has some disadvantages ingenerating high titer recombinant vectors andmanipulating to mediate in viro gene transfer. In thispaper, recombinant vaccinia virus vector encoding
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.
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Antitumor effects of combined transfer of suicidegene and cytokine gene were investigated in this report.Adenovirus harboring E.coli. cytosine deaminase (CD)gene (Ad-CD) and murine interleukin 2 (IL-2) gene(Ad-IL-2) were used for gene transfer in vitro and invivo. C57BL/6 mice were inoculated subcutaneously withB16F10 melanoma cells and three days later treated withadenovirus injection at the site of tumor inoculation.Significant inhibition of tumor growth was achieved
文摘Numerous animal experiments and clinical trialshave demonstrated that the effects of systemicantitumor immune responses are closely correlatedwith the infiltration of effector cells, e. g.macrophages, T cells and NK cells, at the site oftumor. In previous studies, we have established theIL-2, IL-4, IL-6 gene-transfected B16F10
文摘Macrophage inflammatory protein-l, a recentlycharacterized chemokine, consists of two chains (αand β). MIP-lα has been shown to exert strongchemotactic effect on neutrophils, monocytes and Tlymphocytes. In the present study, the B16 melanomacells were transfected with recombinant adenoviruscontaining MIP-lα gene. The biological characteri-zation of the MIP-1α gene transfected B16 melanomacells was investigated. The level of MIP-1α in thesupernatant of gene-transfected melanoma cells was368±24 ng/ml/10~6/24hr.. By using Boyden chambersystem, this supernatant showed strong chemotacticactivity for NK cells, CD4^+ T cells, CD8^+ T cells orthe freshly isolated peritoneal macrophages in vitro.Though the in vitro growth of the gene-transfected B16 melanoma cclls was not aftered, the in vivogrowth of the tumor cells subcutaneously inoculatedwas significantly inhibited. The infiltration ofinflammatory cells into the tumor mass formed bygene-transfected B16 cells was much more obviousthan that by
文摘Recent studies suggest that MHC class Ⅱ genetransfer could stimulate protective antitumor immunity.Whether xenogeneic MHC Ⅱ transfected tumor cells havethese effect is unknown. In this study, HLA-DR3 α and βchain cDNA were cloned by RT-PCR from human Blymphoma Raji cell line and confirmed by DNAsequencing. The recombinant expressing vectors wereconstructed by inserting the α and β chain cDNA intoPCEP4/pLXSN vectors respectively. After transfectingby lipofectamine and selecting with G418 and Hyg, theHLA-DR3 transfected mouse melanoma B16 recombinantclones were obtained. Approximately 59% of
基金Supported by the National Natural Sciences Foundation of China(No.30873010)National High Technology R&D Program of China(No.2006AA02Z481No.2009AA02Z403)
文摘Signal transducers and activators of transcription-3(STAT3),a central cytoplasmic transcription factor,is frequently overexpressed and constitutively activated during malignant transformation.The overexpression of STAT3 in melanoma cells is often observed and is suggested to be involved in tumorigenesis and development.In this study,we designed several
文摘The murine interleukin-2 gene was introduced intomurine melanoma B16 cells by retroviral vector. AfterG418 selection, a clone stably secreting high level ofinterleukin-2 (1038IU per 10~6 cells per 24 hours) wasobtained. The tumorigenicity of this clone decreasedsignificantly as compared with parental tumor cells andtumor cells transferred neomycin gene. There was notumor developed after injection of 5×10~5 IL2-transfectedB16 cells into C57BL/6 mice. However when the
文摘OBJECTIVE Forsythiae Fructus(Lianqiao)is a typical heat-clearing and detoxicating traditional Chinese medicine(TCM)herb,which has been traditionally used for treating cancer according to TCM theory.However,the underlying mechanism has not been fully explained.METHODS In this study,we investigated the antitumor effect of Forsythiae Fructus aqueous extract(FAE)on B16-F10 melanoma.RESULTS FAE strongly inhibited the tumor growth and metastasis formation in B16-F10 melanoma transplanted mice.The survival time of tumor-bearing mice was also significantly prolonged by FAE.The levels of ROS,MDA,TNF-αand IL-6 decreased,while GSH increased in the FAE treatment group,indicating FAE possesses strong anti-oxidative and anti-inflammatory activity.Western blotting analysis demonstrated that antioxidant proteins Nrf2 and HO-1,tumor suppressors P53 and p-PTEN,and the MAPK pathways in tumor tissues were upregulated by FAE treatment.Serum metabolomics analysis further uncovered that 17 metabolites mostly involving in glycerophospholipid metabolism were correlated with the antitumor effect of FAE.Notably,several lysophosphatidylcholines(LysoPCs)significantly decreased in tumor model group,while FAE treatment restored the changes of these phospholipids to about normal condition.LysoPC acyltransferase 1(LPCAT1)and autotaxin(ATX)highly expressed in melanoma and markedly downregulated by FAE were believed to be responsible for this modulation.CONCLUSION FAE exhibites strong antitumor activity against B16-F10 melanoma through activating MAPKs/Nrf2/HO-1 mediated anti-oxidation and anti-inflammation and modulating glycerophospholipid metabolism via downregulating LPCAT1 and ATX.Besides,it is suggested that serum LysoPCs could be potential biomarkers for the diagnosis and prognosis of melanoma.
文摘Aim Forsythia suspensa （Thunb.） Vahl, Lianqiao in Chinese, is one of the most fundamental herbs in traditional Chinese medicine （TCM） with heat-clearing and detoxicating properties. In this study, we aimed to study the antitumor activity of Lianqiao aqueous extract against melanoma using cancer cell line-based in vitro and mouse allografl tumor in vivo models. Furthermore, we also investigated the underlying molecular mechanisms, par- ticularly the involvement of anti-inflammation and anti-oxidation properties in its antitumor activity. Methods The proliferation of cancer cells was measured by MTT assay. The transplanted B16-F10 melanoma in C57BL/6 mice were established and used for the evaluation of in vivo antitumor effect of LQ. Tumor growth was monitored twice a week. Ki67 and CD31 were used to detect cancer cell proliferation and angiogenesis in tumor, respectively. The anti-oxidative property of LQ was determined by measuring the levels of ROS, MDA and GSH. The anti-inflamma- tory effect of LQ was evaluated by measuring TNF-α and IL-6 using ELISA kits. Other protein expression was deter- mined by Western Blot. Results LQ strongly inhibited the growth of B16-F10 cells in vitro and the tumor growth in vivo. The survival time of tumor-bearing mice was significantly prolonged by LQ. LQ inhibited cancer cell prolif- eration and angiogenesis in tumor as evidenced by decreased expressions of Ki67 and CD31. Levels of ROS, MDA TNF-α and IL-6 decreased, while GSH increased in LQ treatment group, indicating a strong anti-oxidative and an- ti-inflammatory activity of LQ. The expression of antioxidant proteins Nff-2 and HO-1, tumor suppressors P53 and p-PTEN, and the MAPK pathways in tumor tissues were upregulated by LQ treatment. Conclusions LQ exhibited strong antitumor activity against B16-F10 murine melanoma both in vitro and in vivo. The antitumor effect of LQ in- volved the decreased oxidative stress and inflammation in tumor, which is closely related to the heat-clearing and detoxicating properties of LQ.
