Our previous research demonstrated that the Wenxia Changfu Formula(WCF),as a neoadjuvant therapy,inhibits M2 macrophage infiltration in the tumor microenvironment and prevents lung cancer metastasis.Given tumor-associ...Our previous research demonstrated that the Wenxia Changfu Formula(WCF),as a neoadjuvant therapy,inhibits M2 macrophage infiltration in the tumor microenvironment and prevents lung cancer metastasis.Given tumor-associated macrophages(TAMs)in epithelial-mesenchymal transition(EMT),this study investigated whether WCF impedes lung cancer metastasis by attenuating TAM-induced EMT in non-small cell lung cancer(NSCLC)cells.Utilizing a co-culture model treated with or without WCF,we observed that WCF downregulated cluster of differentiation 163(CD163)expression in macrophages,reduced CCL18 levels in the conditioned medium,and inhibited the growth,invasion,and EMT of NSCLC cells induced by macrophage co-culture.Manipulation of CCL18 levels and Src overexpression in NSCLC cells revealed that WCF’s effects are mediated through CCL18 and Src signaling.In vivo,WCF inhibited recombinant CCL18(rCCL18)-induced tumor metastasis in nude mice by blocking Src signaling.These findings indicate that WCF inhibits NSCLC metastasis by impeding TAM-induced EMT via antagonistic modulation of CCL18,providing evidence for its potential development and clinical application in NSCLC patients.展开更多
BACKGROUND Chronic hepatitis B virus infection remains a major global public health problem.Peginterferon-alpha-2a(PEG-IFN)has direct antiviral and immunoregulatory effects,and it has become one of the first choice dr...BACKGROUND Chronic hepatitis B virus infection remains a major global public health problem.Peginterferon-alpha-2a(PEG-IFN)has direct antiviral and immunoregulatory effects,and it has become one of the first choice drugs for the treatment of chronic hepatitis B(CHB).Cytokines play an important role in immunity,and they directly inhibit viral replication and indirectly determine the predominant pattern of the host immune response.AIM To determine the correlation between cytokine/chemokine expression levels and response to PEG-IFN treatment in patients with CHB.METHODS Forty-six kinds of cytokines were analyzed before PEG-IFN therapy and at 24 wk during therapy in 26 CHB patients.RESULTS The monokine induced by INF-γ(CXCL9)and serum interferon-inducible protein 10(IP-10)levels at baseline were higher in virological responders than in nonvirological responders(NRs)and decreased during treatment,whereas the NRs did not exhibit significant changes.The macrophage inflammatory protein 1d(MIP-1d)levels at baseline and during treatment were significantly higher in the virological responders than in the NRs,while thymus and activation-regulated chemokine(TARC)levels at baseline and during treatment were significantly lower in the virological responders than in the NRs.The CXCL9,IP-10,MIP-1d,and TARC baseline levels exhibited the expected effects for interferon treatment.The area under the receiver operating characteristic curve values of CXCL9,IP-10,MIP-1d,and TARC for predicting virological responses were 0.787,0.799,0.787,and 0.77(P=0.01,0.013,0.01,and 0.021),respectively.CONCLUSION We found that cytokine levels before and during treatment may represent potential biomarkers to select CHB patients who can respond to PEG-IFN.Therefore,cytokines can be used as an indicator of antiviral drug selection before CHB treatment.展开更多
基金supported by the National Natural Science Foundation of China(No.82274406,81774198)Zhejiang Provincial Natural Science Foundation of China(No.LZ24H270001)the Postgraduate Scientific Research Fund of Zhejiang Chinese Medical University(No.2022YKJ14).
文摘Our previous research demonstrated that the Wenxia Changfu Formula(WCF),as a neoadjuvant therapy,inhibits M2 macrophage infiltration in the tumor microenvironment and prevents lung cancer metastasis.Given tumor-associated macrophages(TAMs)in epithelial-mesenchymal transition(EMT),this study investigated whether WCF impedes lung cancer metastasis by attenuating TAM-induced EMT in non-small cell lung cancer(NSCLC)cells.Utilizing a co-culture model treated with or without WCF,we observed that WCF downregulated cluster of differentiation 163(CD163)expression in macrophages,reduced CCL18 levels in the conditioned medium,and inhibited the growth,invasion,and EMT of NSCLC cells induced by macrophage co-culture.Manipulation of CCL18 levels and Src overexpression in NSCLC cells revealed that WCF’s effects are mediated through CCL18 and Src signaling.In vivo,WCF inhibited recombinant CCL18(rCCL18)-induced tumor metastasis in nude mice by blocking Src signaling.These findings indicate that WCF inhibits NSCLC metastasis by impeding TAM-induced EMT via antagonistic modulation of CCL18,providing evidence for its potential development and clinical application in NSCLC patients.
基金Supported by National Natural Science Foundation of China,No.81872036Talent Innovation and Entrepreneurship Plan of Chengguan District of Lanzhou City,No.2019RCCX0038Science and Technology Plan of Chengguan District of Lanzhou City,No.2019JSXC0092.
文摘BACKGROUND Chronic hepatitis B virus infection remains a major global public health problem.Peginterferon-alpha-2a(PEG-IFN)has direct antiviral and immunoregulatory effects,and it has become one of the first choice drugs for the treatment of chronic hepatitis B(CHB).Cytokines play an important role in immunity,and they directly inhibit viral replication and indirectly determine the predominant pattern of the host immune response.AIM To determine the correlation between cytokine/chemokine expression levels and response to PEG-IFN treatment in patients with CHB.METHODS Forty-six kinds of cytokines were analyzed before PEG-IFN therapy and at 24 wk during therapy in 26 CHB patients.RESULTS The monokine induced by INF-γ(CXCL9)and serum interferon-inducible protein 10(IP-10)levels at baseline were higher in virological responders than in nonvirological responders(NRs)and decreased during treatment,whereas the NRs did not exhibit significant changes.The macrophage inflammatory protein 1d(MIP-1d)levels at baseline and during treatment were significantly higher in the virological responders than in the NRs,while thymus and activation-regulated chemokine(TARC)levels at baseline and during treatment were significantly lower in the virological responders than in the NRs.The CXCL9,IP-10,MIP-1d,and TARC baseline levels exhibited the expected effects for interferon treatment.The area under the receiver operating characteristic curve values of CXCL9,IP-10,MIP-1d,and TARC for predicting virological responses were 0.787,0.799,0.787,and 0.77(P=0.01,0.013,0.01,and 0.021),respectively.CONCLUSION We found that cytokine levels before and during treatment may represent potential biomarkers to select CHB patients who can respond to PEG-IFN.Therefore,cytokines can be used as an indicator of antiviral drug selection before CHB treatment.
