Hepatitis B virus(HBV)infection is a major public health burden.In HBV endemic regions,high prevalence is also correlated with the infections acquired in infancy through perinatal transmission or early childhood expos...Hepatitis B virus(HBV)infection is a major public health burden.In HBV endemic regions,high prevalence is also correlated with the infections acquired in infancy through perinatal transmission or early childhood exposure to HBV,the socalled mother-to-child transmission(MTCT).Children who are infected with HBV at a young age are at higher risk of developing chronic HBV infection than those infected as adults,which may lead to worse clinical outcome.To reduce the incidence of HBV MTCT,several interventions for the infants or the mothers,or both,are already carried out.This review explores the newest information and approaches available in literature regarding HBV MTCT prevalence and its challenges,especially in high HBV endemic countries.This covers HBV screening in pregnant women,prenatal intervention,infant immunoprophylaxis,and postvaccination serological testing for children.展开更多
Targeted therapy has achieved significant success in the treatment of non-small cell lung cancer(NSCLC),particularly in patients harboring common oncogenic driver mutations such as EGFR,KRAS,and ALK rearrangement.Howe...Targeted therapy has achieved significant success in the treatment of non-small cell lung cancer(NSCLC),particularly in patients harboring common oncogenic driver mutations such as EGFR,KRAS,and ALK rearrangement.However,~35–50%of NSCLC patients without tyrosine kinase mutation or rearrangement(non-mutated)cannot benefit from these targeted treatments,highlighting the urgent need for novel therapeutic strategies for this patient population.In this study,we report a non-canonical role of human secretory ribonuclease 1(RNase1),which binds to and activates wild-type ALK in lung cancer cells,thereby triggering its downstream signaling pathway.RNase1-driven ALK-activation(RDAA)cells exhibit enhanced cell proliferation,migration,and colony formation.Additionally,RDAA facilitates tumor formation in fibroblast models,further underscoring its oncogenic potential in vivo.Importantly,RDAA lung cancer cells exhibit marked sensitivity to FDA-approved ALK inhibitors.Tumor growth suppression and survival were substantially improved in both RDAA-positive NSCLC cell line-derived and patient-derived xenograft tumor models treated with ALK inhibitors.Monoclonal antibodies against RNase1 and phosphorylated-ALK were used to analyze two different human NSCLC tissue cohorts by immunohistochemical staining identified 10.4%(5/48)and 8.5%(100/1173)patients who were RDAA positive,respectively.Notably,among the nine RDAA-positive NSCLC patients who accepted ALK inhibitor treatment,five achieved objective response including two who experienced complete response(CR).Together,the current study identifies RDAA as an oncogenic driver and proposes an effective targeted therapy strategy for non-mutated NSCLC patients.展开更多
Background:To address the need for immunotherapy in patients with advanced primary hepatocellular carcinoma(HCC),combination with radiotherapy(RT)has emerged as a promising strategy.In preclinical studies,irradiated t...Background:To address the need for immunotherapy in patients with advanced primary hepatocellular carcinoma(HCC),combination with radiotherapy(RT)has emerged as a promising strategy.In preclinical studies,irradiated tumors released tumor antigens to synergistically increase the antitumor effect of immunotherapy.Hence,we investigated whether RT enhances the efficacy of anti-programmed death receptor-1(PD-1)inhibitors in advanced HCC in real-world practice.Methods:Between August 2018 and June 2021,172 patients with advanced primary HCC were enrolled in the tertiary center(Zhongshan Hospital of Fudan University);95 were treated with a combination of RT and the inhibitor of PD-1(RT-PD1 cohort),and 77 were administered anti-PD-1 therapy(PD1 cohort).The first cycle of PD-1 inhibitors was administered within 60 days or concurrently with RT.Propensity score matching for bias reduction was used to evaluate the clinical outcomes.Results:Among 71 propensity-matched pairs,median progression-free survival was 5.7 months in the RT-PD1 cohort vs.2.9 months in the PD1 cohort(P<0.001).Median overall survival was 20.9 months in the RT-PD1 cohort vs.11.2 months in the PD1 cohort(P=0.018).Compared with patients in the PD1 cohort,patients in the RT-PD1 cohort had significantly higher objective response rates(40.8%,29/71 vs.19.7%,14/71,P=0.006)and disease control rates(62.0%,44/71 vs.31.0%,22/71,P<0.001).The incidences of toxic effects were not significantly different between the two cohorts.Conclusions:RT plus anti-PD-1 therapy is well tolerated.RT enhances the efficacy of anti-PD-1 therapy in patients with advanced primary HCC by improving survival outcomes without increased toxic effects.展开更多
基金Supported by Rumah Program 2024 of Research Organization for Health,National Research and Innovation Agency(BRIN)of Indonesia.
文摘Hepatitis B virus(HBV)infection is a major public health burden.In HBV endemic regions,high prevalence is also correlated with the infections acquired in infancy through perinatal transmission or early childhood exposure to HBV,the socalled mother-to-child transmission(MTCT).Children who are infected with HBV at a young age are at higher risk of developing chronic HBV infection than those infected as adults,which may lead to worse clinical outcome.To reduce the incidence of HBV MTCT,several interventions for the infants or the mothers,or both,are already carried out.This review explores the newest information and approaches available in literature regarding HBV MTCT prevalence and its challenges,especially in high HBV endemic countries.This covers HBV screening in pregnant women,prenatal intervention,infant immunoprophylaxis,and postvaccination serological testing for children.
基金The CAMS Innovation Fund for Medical Sciences(CIFMS,grant no.2021-I2M-C&T-A-021 to L.-X.L)the 1.3.5 Project for Disciplines of Excellence(Grants ZYJC21002 to L.-X.L.)+1 种基金National Institutes of Health Cancer Center Support Grant(P30CA016672 to M.-C.H.)The University of Texas MD Anderson-China Medical University and Hospital Sister Institution Fund(to M.-C.H.).
文摘Targeted therapy has achieved significant success in the treatment of non-small cell lung cancer(NSCLC),particularly in patients harboring common oncogenic driver mutations such as EGFR,KRAS,and ALK rearrangement.However,~35–50%of NSCLC patients without tyrosine kinase mutation or rearrangement(non-mutated)cannot benefit from these targeted treatments,highlighting the urgent need for novel therapeutic strategies for this patient population.In this study,we report a non-canonical role of human secretory ribonuclease 1(RNase1),which binds to and activates wild-type ALK in lung cancer cells,thereby triggering its downstream signaling pathway.RNase1-driven ALK-activation(RDAA)cells exhibit enhanced cell proliferation,migration,and colony formation.Additionally,RDAA facilitates tumor formation in fibroblast models,further underscoring its oncogenic potential in vivo.Importantly,RDAA lung cancer cells exhibit marked sensitivity to FDA-approved ALK inhibitors.Tumor growth suppression and survival were substantially improved in both RDAA-positive NSCLC cell line-derived and patient-derived xenograft tumor models treated with ALK inhibitors.Monoclonal antibodies against RNase1 and phosphorylated-ALK were used to analyze two different human NSCLC tissue cohorts by immunohistochemical staining identified 10.4%(5/48)and 8.5%(100/1173)patients who were RDAA positive,respectively.Notably,among the nine RDAA-positive NSCLC patients who accepted ALK inhibitor treatment,five achieved objective response including two who experienced complete response(CR).Together,the current study identifies RDAA as an oncogenic driver and proposes an effective targeted therapy strategy for non-mutated NSCLC patients.
基金National Natural Science Foundation of China(No.82073479)
文摘Background:To address the need for immunotherapy in patients with advanced primary hepatocellular carcinoma(HCC),combination with radiotherapy(RT)has emerged as a promising strategy.In preclinical studies,irradiated tumors released tumor antigens to synergistically increase the antitumor effect of immunotherapy.Hence,we investigated whether RT enhances the efficacy of anti-programmed death receptor-1(PD-1)inhibitors in advanced HCC in real-world practice.Methods:Between August 2018 and June 2021,172 patients with advanced primary HCC were enrolled in the tertiary center(Zhongshan Hospital of Fudan University);95 were treated with a combination of RT and the inhibitor of PD-1(RT-PD1 cohort),and 77 were administered anti-PD-1 therapy(PD1 cohort).The first cycle of PD-1 inhibitors was administered within 60 days or concurrently with RT.Propensity score matching for bias reduction was used to evaluate the clinical outcomes.Results:Among 71 propensity-matched pairs,median progression-free survival was 5.7 months in the RT-PD1 cohort vs.2.9 months in the PD1 cohort(P<0.001).Median overall survival was 20.9 months in the RT-PD1 cohort vs.11.2 months in the PD1 cohort(P=0.018).Compared with patients in the PD1 cohort,patients in the RT-PD1 cohort had significantly higher objective response rates(40.8%,29/71 vs.19.7%,14/71,P=0.006)and disease control rates(62.0%,44/71 vs.31.0%,22/71,P<0.001).The incidences of toxic effects were not significantly different between the two cohorts.Conclusions:RT plus anti-PD-1 therapy is well tolerated.RT enhances the efficacy of anti-PD-1 therapy in patients with advanced primary HCC by improving survival outcomes without increased toxic effects.
