In the ever-evolving landscape of cancer research and treatment,the quest for novel and non-invasive imaging techniques has become crucial for accurate diagnosis and effective therapy.This study[1]successfully develop...In the ever-evolving landscape of cancer research and treatment,the quest for novel and non-invasive imaging techniques has become crucial for accurate diagnosis and effective therapy.This study[1]successfully developed a good manufacturing practices(GMP)grade ^(89)Zr-labeled anti-Claudin18.2(CLDN18.2)recombinant humanized antibody TST001.^(89)Zr-DFO-TST001 exhibited high radiochemical purity(>99%)and specific activity(24.15±1.34 GBq/mmol).It demonstrated good specificity and rapid tumor accumulation in vivo and in vivo.Through immuno-PET imaging,it enables non-invasive visualization and quantification of CLDN18.2 expression level in CLDN18.2-positive gastrointestinal tumor models.展开更多
Claudin-18.2(CLDN18.2)is a tight junction protein that is typically expressed only in normal gastric mucosal cells.When malignancy occurs,cell polarity is lost,intercellular adhesion structures are destroyed,and CLDN1...Claudin-18.2(CLDN18.2)is a tight junction protein that is typically expressed only in normal gastric mucosal cells.When malignancy occurs,cell polarity is lost,intercellular adhesion structures are destroyed,and CLDN18.2 is therefore exposed to the surface of tumor cells[1].CLDN18.2 is specifically expressed in approximately 40%of human epidermal growth factor receptor 2(HER2)-negative gastrointestinal cancers,making it a promising emerging therapeutic target.As recently reported,zolbetuximab,an CLDN18.2 targeting antibody,has shown amazing efficacy in patients with CLDN18.2-positive and HER2-negative gastric cancers[2].In clinical practice,the assessment of CLDN18.2 expression status is crucial to the determination of treatment regimen for patients.Molecular imaging can be used as a non-invasive test for diagnosis,staging,and efficacy monitoring.The results of molecular imaging of CLDN18.2 have been published continuously,and the development of CLDN18.2 molecular probe is of great significance for the development of tumor targeted therapy(Fig.1).展开更多
Background Patients with single station mediastinal lymph node （N2） non-small call lung ccancer （NSCLC） have a better prognosis than those with multilevel N2.The molecular factors which are involved in disease pro...Background Patients with single station mediastinal lymph node （N2） non-small call lung ccancer （NSCLC） have a better prognosis than those with multilevel N2.The molecular factors which are involved in disease progression remain largely unknown.The purpose of this study was to investigate gene expression differences between single station and multilevel N2 NSCLC and to identify the crucial molecular factors which are associated with progress and prognosis of stage N2 NSCLC.Methods Gene expression analysis was performed using Agilent 4x44K Whole Human Genome Oligo Microarray on 10 freshfrozen lymph node tissue samples from single station N2 and paired multilevel N2 NSCLC patients.Real-time reverse transcription （RT）-PCR was used to validate the differential expression of 14 genes selected by cDNA microarray of which four were confirmed.Immunohistochemical staining for these validated genes was performed on formalin-fixed,paraffinembedded tissue samples from 130 cases of stage N2 NSCLC arranged in a high-density tissue microarray.Results We identified a 14 gene expression signature by comparative analysis of gene expression.Expression of these genes strongly differed between single station and multilevel N2 NSCLC.Four genes （ADAM28,MUC4,CLDN1,and IGF2） correlated with the results of microarray and real-time RT-PCR analysis for the gene-expression data in samples from 56 NSCLC patients.Immunohistochemical staining for these genes in samples from 130 cases of stage N2 NSCLC demonstrated the expression of IGF2 and CLDN1 was negatively correlated with overall survival of stage N2 NSCLC.Conclusions Our results suggest that the expression of CLDN1 and IGF2 indicate a poor prognosis in stage N2 NSCLC.Further,CLDN1 and IGF2 may provide potential targeting opportunities in future therapies.展开更多
基金supported by the National University of Singapore(Grant Nos.:NUHSRO/2021/097/Startup/13,NUHSRO/2020/133/Startup/08,NUHSRO/2023/008/NUSMed/TCE/LOA,NUHSRO/2021/034/TRP/09/Nanomedicine,and NUHSRO/2021/044/Kickstart/09/LOA)National Medical Research Council(Grant Nos.:OFYIRG23jan-0025,OFYIRG23jan-0017,MOH-001254-01,and CG21APR1005)+2 种基金Singapore Ministry of Education Academic Research Fund(Grant Nos.:NUHSRO/2022/093/T1/Seed-Sep/06 and MOE-000387-01)National Research Foundation(Grant No.:CRP28-2022RS-0001),National Natural Science Foundation of China(Grant No.:82202206)Beijing Natural Science Foundation(Grant No.:7224365).
文摘In the ever-evolving landscape of cancer research and treatment,the quest for novel and non-invasive imaging techniques has become crucial for accurate diagnosis and effective therapy.This study[1]successfully developed a good manufacturing practices(GMP)grade ^(89)Zr-labeled anti-Claudin18.2(CLDN18.2)recombinant humanized antibody TST001.^(89)Zr-DFO-TST001 exhibited high radiochemical purity(>99%)and specific activity(24.15±1.34 GBq/mmol).It demonstrated good specificity and rapid tumor accumulation in vivo and in vivo.Through immuno-PET imaging,it enables non-invasive visualization and quantification of CLDN18.2 expression level in CLDN18.2-positive gastrointestinal tumor models.
文摘Claudin-18.2(CLDN18.2)is a tight junction protein that is typically expressed only in normal gastric mucosal cells.When malignancy occurs,cell polarity is lost,intercellular adhesion structures are destroyed,and CLDN18.2 is therefore exposed to the surface of tumor cells[1].CLDN18.2 is specifically expressed in approximately 40%of human epidermal growth factor receptor 2(HER2)-negative gastrointestinal cancers,making it a promising emerging therapeutic target.As recently reported,zolbetuximab,an CLDN18.2 targeting antibody,has shown amazing efficacy in patients with CLDN18.2-positive and HER2-negative gastric cancers[2].In clinical practice,the assessment of CLDN18.2 expression status is crucial to the determination of treatment regimen for patients.Molecular imaging can be used as a non-invasive test for diagnosis,staging,and efficacy monitoring.The results of molecular imaging of CLDN18.2 have been published continuously,and the development of CLDN18.2 molecular probe is of great significance for the development of tumor targeted therapy(Fig.1).
基金Thiswork was supported by grants from National Natural Science Foundation of China （No. 30801377, No. 81000899, No. 81201649） and Tianjin Municipal Science and Technology Commission Key Application Research Project （No. 11JCZDJC 18900）.
文摘Background Patients with single station mediastinal lymph node （N2） non-small call lung ccancer （NSCLC） have a better prognosis than those with multilevel N2.The molecular factors which are involved in disease progression remain largely unknown.The purpose of this study was to investigate gene expression differences between single station and multilevel N2 NSCLC and to identify the crucial molecular factors which are associated with progress and prognosis of stage N2 NSCLC.Methods Gene expression analysis was performed using Agilent 4x44K Whole Human Genome Oligo Microarray on 10 freshfrozen lymph node tissue samples from single station N2 and paired multilevel N2 NSCLC patients.Real-time reverse transcription （RT）-PCR was used to validate the differential expression of 14 genes selected by cDNA microarray of which four were confirmed.Immunohistochemical staining for these validated genes was performed on formalin-fixed,paraffinembedded tissue samples from 130 cases of stage N2 NSCLC arranged in a high-density tissue microarray.Results We identified a 14 gene expression signature by comparative analysis of gene expression.Expression of these genes strongly differed between single station and multilevel N2 NSCLC.Four genes （ADAM28,MUC4,CLDN1,and IGF2） correlated with the results of microarray and real-time RT-PCR analysis for the gene-expression data in samples from 56 NSCLC patients.Immunohistochemical staining for these genes in samples from 130 cases of stage N2 NSCLC demonstrated the expression of IGF2 and CLDN1 was negatively correlated with overall survival of stage N2 NSCLC.Conclusions Our results suggest that the expression of CLDN1 and IGF2 indicate a poor prognosis in stage N2 NSCLC.Further,CLDN1 and IGF2 may provide potential targeting opportunities in future therapies.
