Objective:Patient-derived xenograft(PDX)models have shown great promise in preclinical and translational applications,but their consistency with primary tumors in phenotypic,genetic,and pharmacodynamic heterogeneity h...Objective:Patient-derived xenograft(PDX)models have shown great promise in preclinical and translational applications,but their consistency with primary tumors in phenotypic,genetic,and pharmacodynamic heterogeneity has not been well-studied.This study aimed to establish a PDX repository for non-small cell lung cancer(NSCLC)and to further elucidate whether it could preserve the heterogeneity within and between tumors in patients.Methods:A total of 75 surgically resected NSCLC specimens were implanted into immunodeficient NOD/SCID mice.Based on the successful establishment of the NSCLC PDX model,we compared the expressions of vimentin,Ki67,EGFR,and PD-L1 proteins between cancer tissues and PDX models using hematoxylin and eosin staining and immunohistochemical staining.In addition,we detected whole gene expression profiling between primary tumors and PDX generations.We also performed whole exome sequencing(WES)analysis in 17 first generation xenografts to further assess whether PDXs retained the patient heterogeneities.Finally,paclitaxel,cisplatin,doxorubicin,atezolizumab,afatininb,and AZD4547 were used to evaluate the responses of PDX models to the standard-of-care agents.Results:A large collection of serially transplantable PDX models for NSCLC were successfully developed.The histology and pathological immunohistochemistry of PDX xenografts were consistent with the patients’tumor samples.WES and RNA-seq further confirmed that PDX accurately replicated the molecular heterogeneities of primary tumors.Similar to clinical patients,PDX models responded differentially to the standard-of-care treatment,including chemo-,targeted-and immuno-therapeutics.Conclusions:Our established PDX models of NSCLC faithfully reproduced the molecular,histopathological,and therapeutic characteristics,as well as the corresponding tumor heterogeneities,which provides a clinically relevant platform for drug screening,biomarker discovery,and translational research.展开更多
In recent years,as a new growth point of China's economic development,small towns are under construction in full swing[1].But with the rapid expansion,many problems that the city scholars and builders think about ...In recent years,as a new growth point of China's economic development,small towns are under construction in full swing[1].But with the rapid expansion,many problems that the city scholars and builders think about have emerged.The problems in the construction of small towns are mainly reflected in the over development of capital,insufficient understanding on culture,deviation of construction strategies,etc.In many small towns,there is an imbalance between the volume and color of buildings,the architectural form is single[2],and the expression of local culture is insufficient.From the perspectives of nature and culture,the architecture of Ciping Town,a mountainous town,is evaluated.In view of the problems found,this paper puts forward its thinking on the buildings in this type of small towns,so as to provide some reference for the development of architecture in this type of small towns.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.81101143,81572617,and 81630101)the Sichuan Province Science and Technology Support Program(Grant Nos.2019JDRC0019 and 2018SZ0009)+2 种基金1.3.5 project for disciplines of excellence,West China Hospital,Sichuan University(Grant No.ZYJC18026)The Science and Technology Project of the Health Planning Committee of Sichuan(Grant No.19PJ242)Chengdu science and technology Support Program(Grant No.2019-YFYF-00090-SN)。
文摘Objective:Patient-derived xenograft(PDX)models have shown great promise in preclinical and translational applications,but their consistency with primary tumors in phenotypic,genetic,and pharmacodynamic heterogeneity has not been well-studied.This study aimed to establish a PDX repository for non-small cell lung cancer(NSCLC)and to further elucidate whether it could preserve the heterogeneity within and between tumors in patients.Methods:A total of 75 surgically resected NSCLC specimens were implanted into immunodeficient NOD/SCID mice.Based on the successful establishment of the NSCLC PDX model,we compared the expressions of vimentin,Ki67,EGFR,and PD-L1 proteins between cancer tissues and PDX models using hematoxylin and eosin staining and immunohistochemical staining.In addition,we detected whole gene expression profiling between primary tumors and PDX generations.We also performed whole exome sequencing(WES)analysis in 17 first generation xenografts to further assess whether PDXs retained the patient heterogeneities.Finally,paclitaxel,cisplatin,doxorubicin,atezolizumab,afatininb,and AZD4547 were used to evaluate the responses of PDX models to the standard-of-care agents.Results:A large collection of serially transplantable PDX models for NSCLC were successfully developed.The histology and pathological immunohistochemistry of PDX xenografts were consistent with the patients’tumor samples.WES and RNA-seq further confirmed that PDX accurately replicated the molecular heterogeneities of primary tumors.Similar to clinical patients,PDX models responded differentially to the standard-of-care treatment,including chemo-,targeted-and immuno-therapeutics.Conclusions:Our established PDX models of NSCLC faithfully reproduced the molecular,histopathological,and therapeutic characteristics,as well as the corresponding tumor heterogeneities,which provides a clinically relevant platform for drug screening,biomarker discovery,and translational research.
文摘In recent years,as a new growth point of China's economic development,small towns are under construction in full swing[1].But with the rapid expansion,many problems that the city scholars and builders think about have emerged.The problems in the construction of small towns are mainly reflected in the over development of capital,insufficient understanding on culture,deviation of construction strategies,etc.In many small towns,there is an imbalance between the volume and color of buildings,the architectural form is single[2],and the expression of local culture is insufficient.From the perspectives of nature and culture,the architecture of Ciping Town,a mountainous town,is evaluated.In view of the problems found,this paper puts forward its thinking on the buildings in this type of small towns,so as to provide some reference for the development of architecture in this type of small towns.
