Gastrointestinal(GI)cancer,including esophageal,gastric,and colorectal cancer,is one of the most prevalent types of malignant carcinoma and the leading cause of cancer-related deaths.Despite significant advances in th...Gastrointestinal(GI)cancer,including esophageal,gastric,and colorectal cancer,is one of the most prevalent types of malignant carcinoma and the leading cause of cancer-related deaths.Despite significant advances in therapeutic strategies for GI cancers in recent decades,drug resistance with various mechanisms remains the prevailing cause of therapy failure in GI cancers.Accumulating evidence has demonstrated that the transforming growth factor(TGF)-βsignaling pathway has crucial,complex roles in many cellular functions related to drug resistance.This review summarizes current knowledge regarding the role of the TGF-βsignaling pathway in the resistance of GI cancers to conventional chemotherapy,targeted therapy,immunotherapy,and traditional medicine.Various processes,including epithelial-mesenchymal transition,cancer stem cell development,tumor microenvironment alteration,and microRNA biogenesis,are proposed as the main mechanisms of TGF-β-mediated drug resistance in GI cancers.Several studies have already indicated the benefit of combining antitumor drugs with agents that suppress the TGF-βsignaling pathway,but this approach needs to be verified in additional clinical studies.Moreover,the identification of potential biological markers that can be used to predict the response to TGF-βsignaling pathway inhibitors during anticancer treatments will have important clinical implications in the future.展开更多
Herein we develop a unique differentiated-uptake strategy capable of efficient and high-purity isolation of genuine drug-resistant(DR)cells from three types of drug-surviving cancer cells,which include paclitaxel-surv...Herein we develop a unique differentiated-uptake strategy capable of efficient and high-purity isolation of genuine drug-resistant(DR)cells from three types of drug-surviving cancer cells,which include paclitaxel-surviving human ovarian OVCAR-3 cancer cells and human lung carcinoma A549/Taxol cells,and doxorubicin-surviving human immortalized myelogenous leukemia K562/ADR cells.By using this strategy which relies on fluorescent glycan nanoparticle(FGNP)-based fluorescence-activated cell sorting(FACS)assays,two subpopulations with distinct fluorescences existing in drug-surviving OVCAR-3 cells were separated,and we found that the lower fluorescence(LF)subpopulation consisted of DR cells,while the higher fluorescence(HF)subpopulation was comprised of non-DR cells.Besides,the DR cells and their progenies were found distinct in their increased expression of drug-resistant genes.More intriguingly,by using the FGNP-based FACS assay to detect DR/non-DR phenotypes,we found that the DR phenotype had a potential to differentiate into the non-DR progeny,which demonstrates the differentiation feature of stem-like cancer cells.Further research disclosed that the assay can quantitatively detect the degree of drug resistance in DR cells,as well as the reversal of drug resistance that are tackled by various therapeutic methods.The strategy thus paves the way to develop theranostic approaches associated with chemotherapy-resistance and cancer stemness.展开更多
Erratum to Nano Research 2020,13(11):3110-3122 https://d0i.0rg/l 0.1007/s 12274-020-2981-8 The article Fluorescent glycan nanoparticle-based FACS assays for the identification of genuine drug-resistant cancer cells wi...Erratum to Nano Research 2020,13(11):3110-3122 https://d0i.0rg/l 0.1007/s 12274-020-2981-8 The article Fluorescent glycan nanoparticle-based FACS assays for the identification of genuine drug-resistant cancer cells with differentiation potential,written by Chenglong Wang et al.,was erroneously originally published electronically on the publishers internet portal(currently SpringerLink)on 10 August 2020 with the Acknowledgements.展开更多
基金Supported by Fourth Training Program for the Outstanding Young Talents,Jinshan Health Commission,China,No.JSYQ201904Key Construction Project on Clinical Pharmacy of Shanghai,China,No.2019-1229National Natural Science Foundation of China,No.81872121.
文摘Gastrointestinal(GI)cancer,including esophageal,gastric,and colorectal cancer,is one of the most prevalent types of malignant carcinoma and the leading cause of cancer-related deaths.Despite significant advances in therapeutic strategies for GI cancers in recent decades,drug resistance with various mechanisms remains the prevailing cause of therapy failure in GI cancers.Accumulating evidence has demonstrated that the transforming growth factor(TGF)-βsignaling pathway has crucial,complex roles in many cellular functions related to drug resistance.This review summarizes current knowledge regarding the role of the TGF-βsignaling pathway in the resistance of GI cancers to conventional chemotherapy,targeted therapy,immunotherapy,and traditional medicine.Various processes,including epithelial-mesenchymal transition,cancer stem cell development,tumor microenvironment alteration,and microRNA biogenesis,are proposed as the main mechanisms of TGF-β-mediated drug resistance in GI cancers.Several studies have already indicated the benefit of combining antitumor drugs with agents that suppress the TGF-βsignaling pathway,but this approach needs to be verified in additional clinical studies.Moreover,the identification of potential biological markers that can be used to predict the response to TGF-βsignaling pathway inhibitors during anticancer treatments will have important clinical implications in the future.
基金supported by the National Natural Science Foundation of China(Nos.21871180 and 81872121)the“Shuguang Program”supported by the Shanghai Education Development Foundation and the Shanghai Municipal Education Commission(No.17SG12)+2 种基金the Program for Professor of Special Appointment(Eastern Scholar)at Shanghai Institutions of Higher Learning(No.SHDP201802)the Science and Technology Commission of Shanghai Municipality(No.18520710300 and 17ZR1404100)the Biomedical Interdisciplinary Research Foundation of SJTU(No.YG2019QNB34).
文摘Herein we develop a unique differentiated-uptake strategy capable of efficient and high-purity isolation of genuine drug-resistant(DR)cells from three types of drug-surviving cancer cells,which include paclitaxel-surviving human ovarian OVCAR-3 cancer cells and human lung carcinoma A549/Taxol cells,and doxorubicin-surviving human immortalized myelogenous leukemia K562/ADR cells.By using this strategy which relies on fluorescent glycan nanoparticle(FGNP)-based fluorescence-activated cell sorting(FACS)assays,two subpopulations with distinct fluorescences existing in drug-surviving OVCAR-3 cells were separated,and we found that the lower fluorescence(LF)subpopulation consisted of DR cells,while the higher fluorescence(HF)subpopulation was comprised of non-DR cells.Besides,the DR cells and their progenies were found distinct in their increased expression of drug-resistant genes.More intriguingly,by using the FGNP-based FACS assay to detect DR/non-DR phenotypes,we found that the DR phenotype had a potential to differentiate into the non-DR progeny,which demonstrates the differentiation feature of stem-like cancer cells.Further research disclosed that the assay can quantitatively detect the degree of drug resistance in DR cells,as well as the reversal of drug resistance that are tackled by various therapeutic methods.The strategy thus paves the way to develop theranostic approaches associated with chemotherapy-resistance and cancer stemness.
基金This work was financially supported by the National Natural Science Foundation of China(Nos.21871180 and 81872121)the“Shuguang Program”supported by the Shanghai Education Development Foundation and the Shanghai Municipal Education Commission(No.17SG12)+2 种基金the Program for Professor of Special Appointment(Eastern Scholar)at Shanghai Institutions of Higher Learning(No.SHDP201802)the Science and Technology Commission of Shanghai Municipality(No.18520710300 and 18JC1413500)the Biomedical Interdisciplinary Research Foundation of SJTU(No.YG2019QNB34).
文摘Erratum to Nano Research 2020,13(11):3110-3122 https://d0i.0rg/l 0.1007/s 12274-020-2981-8 The article Fluorescent glycan nanoparticle-based FACS assays for the identification of genuine drug-resistant cancer cells with differentiation potential,written by Chenglong Wang et al.,was erroneously originally published electronically on the publishers internet portal(currently SpringerLink)on 10 August 2020 with the Acknowledgements.