Claudin18.2(CLDN18.2)is a tight junction protein that is overexpressed in a variety of solid tumors such as gastrointestinal cancer and oesophageal cancer.It has been identified as a promising target and a potential b...Claudin18.2(CLDN18.2)is a tight junction protein that is overexpressed in a variety of solid tumors such as gastrointestinal cancer and oesophageal cancer.It has been identified as a promising target and a potential biomarker to diagnose tumor,evaluate efficacy,and determine patient prognosis.TST001 is a recombinant humanized CLDN18.2 antibody that selectively binds to the extracellular loop of human Claudin18.2.In this study,we constructed a solid target radionuclide zirconium-^(89)(^(89)Zr)labled-TST001 to detect the expression of in the human stomach cancer BGC823CLDN18.2 cell lines.The[^(89)Zr]Zr-desferrioxamine(DFO)-TST001 showed high radiochemical purity(RCP,>99%)and specific activity(24.15±1.34 GBq/mmol),and was stable in 5%human serum albumin,and phosphate buffer saline(>85%RCP at 96 h).The EC_(50) values of TST001 and DFO-TST001 were as high as 0.413±0.055 and 0.361±0.058 nM(P>0.05),respectively.The radiotracer had a significantly higher average standard uptake values in CLDN18.2-positive tumors than in CLDN18.2-negative tumors(1.11±0.02 vs.0.49±0.03,P=0.0016)2 days post injection(p.i.).BGC823CLDN18.2 mice models showed high tumor/muscle ratios 96 h p.i.with[^(89)Zr]Zr-DFO-TST001 was much higher than those of the other imaging groups.Immunohistochemistry results showed that BGC823CLDN18.2 tumors were highly positive(+++)for CLDN18.2,while those in the BGC823 group did not express CLDN18.2().The results of ex vivo biodistribution studies showed that there was a higher distribution in the BGC823CLDN18.2 tumor bearing mice(2.05±0.16%ID/g)than BGC823 mice(0.69±0.02%ID/g)and blocking group(0.72±0.02%ID/g).A dosimetry estimation study showed that the effective dose of[^(89)Zr]Zr-DFO-TST001 was 0.0705 mSv/MBq,which is within the range of acceptable doses for nuclear medicine research.Taken together,these results suggest that Good Manufacturing Practices produced by this immuno-positron emission tomography probe can detect CLDN18.2-overexpressing tumors.展开更多
BACKGROUND Early gastric cancer(EGC)is typically treated with endoscopic submucosal dissection(ESD).However,recurrence may occur after ESD,requiring surveillance.AIM To examine the knowledge,attitude,and practice(KAP)...BACKGROUND Early gastric cancer(EGC)is typically treated with endoscopic submucosal dissection(ESD).However,recurrence may occur after ESD,requiring surveillance.AIM To examine the knowledge,attitude,and practice(KAP)of EGC survivors following ESD regarding gastric cancer recurrence.METHODS This cross-sectional study was conducted between June 1,2022 and October 1,2022 in Zhejiang,China.A total of 400 EGC survivors who underwent ESD at the Affiliated Jinhua Hospital,Zhejiang University School of Medicine participated in this study.A self-administered questionnaire was developed to assess KAP monitoring gastric cancer after ESD.RESULTS The average scores for KAP were 3.34,23.76,and 5.75 out of 5,30,and 11,respectively.Pearson correlation analysis revealed positive and significant correlations between knowledge and attitude,knowledge and practice,and attitude and practice(r=0.405,0.511,and 0.458,respectively;all P<0.001).Multivariate logistic regression analysis showed that knowledge,attitude,13-24 mo since the last ESD(vs≤12 mo since the last ESD),and≥25 mo since the last ESD(vs≤12 mo since the last ESD)were independent predictors of proactive practice(odds ratio=1.916,1.253,3.296,and 5.768,respectively,all P<0.0001).CONCLUSION EGC survivors showed inadequate knowledge,positive attitude,and poor practices in monitoring recurrences after ESD.Adequate knowledge,positive attitude,and a longer time since the last ESD were associated with practice.展开更多
Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immunotherapeutic agents...Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immunotherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histocompatibility complex(MHC)class I and II antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4t and CD8t T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.展开更多
AIM:To assess the association between smoking and alcohol consumption and extrahepatic cholangiocarcinoma(ECC)through a meta-analysis of clinical observational studies.METHODS:A literature search was conducted using E...AIM:To assess the association between smoking and alcohol consumption and extrahepatic cholangiocarcinoma(ECC)through a meta-analysis of clinical observational studies.METHODS:A literature search was conducted using Embase and MEDLINE databases from inception to 31May 2013 without language limitations,and by manually searching the references of retrieved articles.Casecontrol and cohort studies that investigated the association between smoking or alcohol consumption and ECC were included.The quality of these studies was assessed using the Newcastle-Ottawa quality assessment scale.Summary relative risks and corresponding95%CI were calculated using a random-effects model.Publication bias was assessed by Begg’s funnel plot and Egger’s test.RESULTS:A total of 12 eligible articles(11 case-control studies and one cohort study)were included in this meta-analysis.Eleven studies reported the association between smoking and ECC.Pooled analysis indicated that smokers had an increased risk of ECC development as compared with non-smokers(summary RR=1.23;95%CI:1.01-1.50).This correlation was present in population-based studies(n=5;summary RR=1.47;95%CI:1.06-2.05)but not in hospital-based studies(n=6;summary RR=1.10;95%CI:0.88-1.37)and in non-Asian regions(n=7;summary RR=1.39;95%CI:1.03-1.87)but not in Asia(n=4;summary RR=1.08;95%CI:0.85-1.38).Seven studies reported an association between consuming alcohol and ECC.Pooled analysis indicated that alcohol drinkers had a similar risk of ECC development as did individuals who did not drink alcohol(summary RR=1.09;95%CI:0.87-1.37).There was moderate heterogeneity among the studies and no evidence of publication bias.CONCLUSION:Smoking is associated with an increased risk of ECC,but alcohol consumption is not.Further population-based studies,particularly cohort studies,are warranted to enable definitive conclusions.展开更多
基金supported by the National Natural Science Foundation of China(81774324)the Fundamental Research Project of Medical and Health in Shenzhen Bao’an District(2022JD224)the Special Research and Development Project for Traditional Chinese Medicine Preparations of Shenzhen Bao’an District Hospitals(2022KJCX-YYZJ-6)
基金The research was funded by the National Natural Science Foundation of China(Grant Nos.:82171973,82171980,and 82102092)Beijing Millions of Talent Projects A Level Funding(Grant No.:2019A38)+2 种基金The study was also supported by Beijing Hospitals Authority Dengfeng Project(Grant No.:DFL20191102)the Pilot Project(4th Round)to Reform Public Development of Beijing Municipal Medical Research Institute(20211)the Third Foster Plan in 2019“Molecular Imaging Probe Preparation and Characterization of Key Technologies and Equipment”for the Development of Key Technologies and Equipment in Major Science and Technology Infrastructure in Shenzhen,China.
文摘Claudin18.2(CLDN18.2)is a tight junction protein that is overexpressed in a variety of solid tumors such as gastrointestinal cancer and oesophageal cancer.It has been identified as a promising target and a potential biomarker to diagnose tumor,evaluate efficacy,and determine patient prognosis.TST001 is a recombinant humanized CLDN18.2 antibody that selectively binds to the extracellular loop of human Claudin18.2.In this study,we constructed a solid target radionuclide zirconium-^(89)(^(89)Zr)labled-TST001 to detect the expression of in the human stomach cancer BGC823CLDN18.2 cell lines.The[^(89)Zr]Zr-desferrioxamine(DFO)-TST001 showed high radiochemical purity(RCP,>99%)and specific activity(24.15±1.34 GBq/mmol),and was stable in 5%human serum albumin,and phosphate buffer saline(>85%RCP at 96 h).The EC_(50) values of TST001 and DFO-TST001 were as high as 0.413±0.055 and 0.361±0.058 nM(P>0.05),respectively.The radiotracer had a significantly higher average standard uptake values in CLDN18.2-positive tumors than in CLDN18.2-negative tumors(1.11±0.02 vs.0.49±0.03,P=0.0016)2 days post injection(p.i.).BGC823CLDN18.2 mice models showed high tumor/muscle ratios 96 h p.i.with[^(89)Zr]Zr-DFO-TST001 was much higher than those of the other imaging groups.Immunohistochemistry results showed that BGC823CLDN18.2 tumors were highly positive(+++)for CLDN18.2,while those in the BGC823 group did not express CLDN18.2().The results of ex vivo biodistribution studies showed that there was a higher distribution in the BGC823CLDN18.2 tumor bearing mice(2.05±0.16%ID/g)than BGC823 mice(0.69±0.02%ID/g)and blocking group(0.72±0.02%ID/g).A dosimetry estimation study showed that the effective dose of[^(89)Zr]Zr-DFO-TST001 was 0.0705 mSv/MBq,which is within the range of acceptable doses for nuclear medicine research.Taken together,these results suggest that Good Manufacturing Practices produced by this immuno-positron emission tomography probe can detect CLDN18.2-overexpressing tumors.
基金the Basic Public Welfare Research Program of Zhejiang Province,No.LGF19H160022and the Key Project of Jinhua Social Development,No.2018-3-001f。
文摘BACKGROUND Early gastric cancer(EGC)is typically treated with endoscopic submucosal dissection(ESD).However,recurrence may occur after ESD,requiring surveillance.AIM To examine the knowledge,attitude,and practice(KAP)of EGC survivors following ESD regarding gastric cancer recurrence.METHODS This cross-sectional study was conducted between June 1,2022 and October 1,2022 in Zhejiang,China.A total of 400 EGC survivors who underwent ESD at the Affiliated Jinhua Hospital,Zhejiang University School of Medicine participated in this study.A self-administered questionnaire was developed to assess KAP monitoring gastric cancer after ESD.RESULTS The average scores for KAP were 3.34,23.76,and 5.75 out of 5,30,and 11,respectively.Pearson correlation analysis revealed positive and significant correlations between knowledge and attitude,knowledge and practice,and attitude and practice(r=0.405,0.511,and 0.458,respectively;all P<0.001).Multivariate logistic regression analysis showed that knowledge,attitude,13-24 mo since the last ESD(vs≤12 mo since the last ESD),and≥25 mo since the last ESD(vs≤12 mo since the last ESD)were independent predictors of proactive practice(odds ratio=1.916,1.253,3.296,and 5.768,respectively,all P<0.0001).CONCLUSION EGC survivors showed inadequate knowledge,positive attitude,and poor practices in monitoring recurrences after ESD.Adequate knowledge,positive attitude,and a longer time since the last ESD were associated with practice.
基金supported by Natural Science Foundation of Shaanxi Province(Grant No.:2019ZY-CXPT-03-01)to Ping Zhu and Key Research and Development Program of Shaanxi Province(Grant No.:2020ZDLSF03-02)to Zhi-Nan Chen and Huijie Bian as well as Tricision Biotherapeutics Inc.
文摘Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immunotherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histocompatibility complex(MHC)class I and II antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4t and CD8t T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.
文摘AIM:To assess the association between smoking and alcohol consumption and extrahepatic cholangiocarcinoma(ECC)through a meta-analysis of clinical observational studies.METHODS:A literature search was conducted using Embase and MEDLINE databases from inception to 31May 2013 without language limitations,and by manually searching the references of retrieved articles.Casecontrol and cohort studies that investigated the association between smoking or alcohol consumption and ECC were included.The quality of these studies was assessed using the Newcastle-Ottawa quality assessment scale.Summary relative risks and corresponding95%CI were calculated using a random-effects model.Publication bias was assessed by Begg’s funnel plot and Egger’s test.RESULTS:A total of 12 eligible articles(11 case-control studies and one cohort study)were included in this meta-analysis.Eleven studies reported the association between smoking and ECC.Pooled analysis indicated that smokers had an increased risk of ECC development as compared with non-smokers(summary RR=1.23;95%CI:1.01-1.50).This correlation was present in population-based studies(n=5;summary RR=1.47;95%CI:1.06-2.05)but not in hospital-based studies(n=6;summary RR=1.10;95%CI:0.88-1.37)and in non-Asian regions(n=7;summary RR=1.39;95%CI:1.03-1.87)but not in Asia(n=4;summary RR=1.08;95%CI:0.85-1.38).Seven studies reported an association between consuming alcohol and ECC.Pooled analysis indicated that alcohol drinkers had a similar risk of ECC development as did individuals who did not drink alcohol(summary RR=1.09;95%CI:0.87-1.37).There was moderate heterogeneity among the studies and no evidence of publication bias.CONCLUSION:Smoking is associated with an increased risk of ECC,but alcohol consumption is not.Further population-based studies,particularly cohort studies,are warranted to enable definitive conclusions.
