Despite therapeutic advancements,the prognosis of locally advanced non-small cell lung cancer(LANSCLC),which has invaded multiple lobes or the other lung and intrapulmonary lymph nodes,remains poor.The emergence of im...Despite therapeutic advancements,the prognosis of locally advanced non-small cell lung cancer(LANSCLC),which has invaded multiple lobes or the other lung and intrapulmonary lymph nodes,remains poor.The emergence of immunotherapy with immune checkpoint blockade(ICB)is transforming cancer treatment.However,only a fraction of lung cancer patients benefit from ICB.Significant clinical evidence suggests that the proinflammatory tumor microenvironment(TME)and programmed death-ligand 1(PD-L1)expression correlate positively with response to the PD-1/PD-L1 blockade.We report here a liposomal nanoparticle loaded with cyclic dinucleotide and aerosolized(AeroNP-CDN)for inhalation delivery to deep-seated lung tumors and target CDN to activate stimulators of interferon(IFN)genes in macrophages and dendritic cells(DCs).Using a mouse model that recapitulates the clinical LANSCLC,we show that AeroNP-CDN efficiently mitigates the immunosuppressive TME by reprogramming tumor-associated macrophage from the M2 to M1 phenotype,activating DCs for effective tumor antigen presentation and increasing tumor-infiltrating CD8+T cells for adaptive anticancer immunity.Intriguingly,activation of interferons by AeroNP-CDN also led to increased PD-L1 expression in lung tumors,which,however,set a stage for response to anti-PD-L1 treatment.Indeed,anti-PD-L1 antibody-mediated blockade of IFNs-induced immune inhibitory PD-1/PD-L1 signaling further prolonged the survival of the LANSCLC-bearing mice.Importantly,AeroNP-CDN alone or combination immunotherapy was safe without local or systemic immunotoxicity.In conclusion,this study demonstrates a potential nano-immunotherapy strategy for LANSCLC,and mechanistic insights into the evolution of adaptive immune resistance provide a rational combination immunotherapy to overcome it.展开更多
[Objectives]To explore the effects of budesonide aerosol inhalation on the perioperative pulmonary function of patients undergoing cardiopulmonary bypass valve replacement.[Methods]A total of 82 patients who underwent...[Objectives]To explore the effects of budesonide aerosol inhalation on the perioperative pulmonary function of patients undergoing cardiopulmonary bypass valve replacement.[Methods]A total of 82 patients who underwent cardiopulmonary bypass valve replacement during January 2018 and May 2019 in the Affiliated Hospital of Chengde Medical College were selected.They were divided into blank control group(group A,n=28),aerosol control group(group B,n=27,normal saline aerosol treatment),and experimental group(group C,n=27,budesonide aerosol treatment)by the random number table method.Corresponding treatments were given 5 d before surgery and 5 d after surgery,and the treatment effects of the 3 groups were compared.[Results]The clinical symptom scores of the patients in the experimental group were significantly lower than those in the blank control group and the aerosol control group,and the total effective rate of treatment was significantly higher than that in the blank control group.[Conclusions]Perioperative application of budesonide aerosol inhalation can effectively improve the clinical symptoms,treatment effect,and clinical prognosis of patients undergoing cardiopulmonary bypass valve replacement.展开更多
Objective To evaluate the effectiveness of a helium oxygen mixture (79%He 21%O 2) as an aerosolizing compressed gas for β 2 agonist therapy in patients with an asthma exacerbation Methods Twenty four pat...Objective To evaluate the effectiveness of a helium oxygen mixture (79%He 21%O 2) as an aerosolizing compressed gas for β 2 agonist therapy in patients with an asthma exacerbation Methods Twenty four patients in the outpatient department with a mild to moderate exacerbation of asthma were enrolled The patients were randomly divided into an experimental group (13 cases) and a control group (11 cases) The experimental group inhaled Berotec with heliox driven, and the control group inhaled Berotec with compressed air driven Eight hospitalized patients in the respiratory department with severe exacerbation of asthma were enrolled The patients inhaled Berotec with heliox driven or compressed air driven in a random order Results The results of spirometric parameters and arterial blood gas analysis were measured In the mild to moderate asthma patients, no statistical differences between the two groups for forced vital capacity (FVC), forced expired volume in one second (FEV 1), and expiratory flow in 50% forced vital capacity (FEF 50 ) were presented But the severe patients showed significant differences between heliox driven and compressed air driven for FVC, FEV 1, FEF 50 and partial pressure of oxygen (PaO 2) Conclusions Compared with the traditional inhalation of β 2 agonist therapy using compressed air driven, the method of inhaling β 2 agonist with heliox driven has more obvious benefits for those suffering from severe asthma This is likely due to the cooperative effects between inhaling heliox on its physical gas properties and improving delivery of β 2 agonist in the treatment of exacerbation of severe asthma展开更多
基金supported in part by NIH/NCI 1R01CA264102-01(D.Z.)Wake Forest Comprehensive Cancer Center P30 CA01219740.A.A.H.is supported by funding from the Department of Veteran’s Affairs(No.2I01BX002559-07)from the National Institutes of Health(No.1R01CA244212-01A1).
文摘Despite therapeutic advancements,the prognosis of locally advanced non-small cell lung cancer(LANSCLC),which has invaded multiple lobes or the other lung and intrapulmonary lymph nodes,remains poor.The emergence of immunotherapy with immune checkpoint blockade(ICB)is transforming cancer treatment.However,only a fraction of lung cancer patients benefit from ICB.Significant clinical evidence suggests that the proinflammatory tumor microenvironment(TME)and programmed death-ligand 1(PD-L1)expression correlate positively with response to the PD-1/PD-L1 blockade.We report here a liposomal nanoparticle loaded with cyclic dinucleotide and aerosolized(AeroNP-CDN)for inhalation delivery to deep-seated lung tumors and target CDN to activate stimulators of interferon(IFN)genes in macrophages and dendritic cells(DCs).Using a mouse model that recapitulates the clinical LANSCLC,we show that AeroNP-CDN efficiently mitigates the immunosuppressive TME by reprogramming tumor-associated macrophage from the M2 to M1 phenotype,activating DCs for effective tumor antigen presentation and increasing tumor-infiltrating CD8+T cells for adaptive anticancer immunity.Intriguingly,activation of interferons by AeroNP-CDN also led to increased PD-L1 expression in lung tumors,which,however,set a stage for response to anti-PD-L1 treatment.Indeed,anti-PD-L1 antibody-mediated blockade of IFNs-induced immune inhibitory PD-1/PD-L1 signaling further prolonged the survival of the LANSCLC-bearing mice.Importantly,AeroNP-CDN alone or combination immunotherapy was safe without local or systemic immunotoxicity.In conclusion,this study demonstrates a potential nano-immunotherapy strategy for LANSCLC,and mechanistic insights into the evolution of adaptive immune resistance provide a rational combination immunotherapy to overcome it.
基金Young Researcher Science and Technology Project of Scientific Research Fund for the Health Commission of Hebei Province(Directive Project:20200182)Self-financing Project for Science and Technology Plan of Chengde City of Hebei Province(202006A048).
文摘[Objectives]To explore the effects of budesonide aerosol inhalation on the perioperative pulmonary function of patients undergoing cardiopulmonary bypass valve replacement.[Methods]A total of 82 patients who underwent cardiopulmonary bypass valve replacement during January 2018 and May 2019 in the Affiliated Hospital of Chengde Medical College were selected.They were divided into blank control group(group A,n=28),aerosol control group(group B,n=27,normal saline aerosol treatment),and experimental group(group C,n=27,budesonide aerosol treatment)by the random number table method.Corresponding treatments were given 5 d before surgery and 5 d after surgery,and the treatment effects of the 3 groups were compared.[Results]The clinical symptom scores of the patients in the experimental group were significantly lower than those in the blank control group and the aerosol control group,and the total effective rate of treatment was significantly higher than that in the blank control group.[Conclusions]Perioperative application of budesonide aerosol inhalation can effectively improve the clinical symptoms,treatment effect,and clinical prognosis of patients undergoing cardiopulmonary bypass valve replacement.
文摘Objective To evaluate the effectiveness of a helium oxygen mixture (79%He 21%O 2) as an aerosolizing compressed gas for β 2 agonist therapy in patients with an asthma exacerbation Methods Twenty four patients in the outpatient department with a mild to moderate exacerbation of asthma were enrolled The patients were randomly divided into an experimental group (13 cases) and a control group (11 cases) The experimental group inhaled Berotec with heliox driven, and the control group inhaled Berotec with compressed air driven Eight hospitalized patients in the respiratory department with severe exacerbation of asthma were enrolled The patients inhaled Berotec with heliox driven or compressed air driven in a random order Results The results of spirometric parameters and arterial blood gas analysis were measured In the mild to moderate asthma patients, no statistical differences between the two groups for forced vital capacity (FVC), forced expired volume in one second (FEV 1), and expiratory flow in 50% forced vital capacity (FEF 50 ) were presented But the severe patients showed significant differences between heliox driven and compressed air driven for FVC, FEV 1, FEF 50 and partial pressure of oxygen (PaO 2) Conclusions Compared with the traditional inhalation of β 2 agonist therapy using compressed air driven, the method of inhaling β 2 agonist with heliox driven has more obvious benefits for those suffering from severe asthma This is likely due to the cooperative effects between inhaling heliox on its physical gas properties and improving delivery of β 2 agonist in the treatment of exacerbation of severe asthma