Breast cancer is the leading cause of cancer-related deaths in women worldwide,with Hormone Receptor(HR)+being the predominant subtype.Tamoxifen(TAM)serves as the primary treatment for HR+breast cancer.However,drug re...Breast cancer is the leading cause of cancer-related deaths in women worldwide,with Hormone Receptor(HR)+being the predominant subtype.Tamoxifen(TAM)serves as the primary treatment for HR+breast cancer.However,drug resistance often leads to recurrence,underscoring the need to develop new therapies to enhance patient quality of life and reduce recurrence rates.Artemisinin(ART)has demonstrated efficacy in inhibiting the growth of drug-resistant cells,positioning art as a viable option for counteracting endocrine resistance.This study explored the interaction between artemisinin and tamoxifen through a combined approach of bioinformatics analysis and experimental validation.Five characterized genes(ar,cdkn1a,erbb2,esr1,hsp90aa1)and seven drug-disease crossover genes(cyp2e1,rorc,mapk10,glp1r,egfr,pgr,mgll)were identified using WGCNA crossover analysis.Subsequent functional enrichment analyses were conducted.Our findings confirm a significant correlation between key cluster gene expression and immune cell infiltration in tamoxifen-resistant and-sensitized patients.scRNA-seq analysis revealed high expression of key cluster genes in epithelial cells,suggesting artemisinin’s specific impact on tumor cells in estrogen receptor(ER)-positive BC tissues.Molecular target docking and in vitro experiments with artemisinin on LCC9 cells demonstrated a reversal effect in reducing migratory and drug resistance of drug-resistant cells by modulating relevant drug resistance genes.These results indicate that artemisinin could potentially reverse tamoxifen resistance in ER-positive breast cancer.展开更多
目的探讨TMX基因在结直肠癌及癌旁组织中的表达是否存在差异。方法对结直肠癌的的石蜡标本及切缘组织各33例,将肿瘤组织和对应的切缘正常组织放置于同一张载玻片上,采用免疫组化方法,利用IPP6.0软件进行半定量分析,研究TMX基因在结直肠...目的探讨TMX基因在结直肠癌及癌旁组织中的表达是否存在差异。方法对结直肠癌的的石蜡标本及切缘组织各33例,将肿瘤组织和对应的切缘正常组织放置于同一张载玻片上,采用免疫组化方法,利用IPP6.0软件进行半定量分析,研究TMX基因在结直肠癌组织中及手术切缘的表达情况,并比较这两组是否存在表达差异。结果 TMX基因在结直肠癌组织及癌旁组织均表达,在结直肠癌组织的表达量明显低于正常切缘(0.142±0.038 VS 0.210±0.037,P<0.0001)。结论 TMX基因在结直肠癌组织的表达量显著低于正常癌旁组织,提示TMX基因可能参与结直肠癌的发病。展开更多
基金supported by the National Natural Science Foundation of China(81973839)High Level Chinese Medical Hospital Promotion Project-Special Project on Formulation R&D and New Drug Translation for Medical Institutions(HLCMHPP2023037)Upgrading the Development and Promotion of about 30 Integrated Chinese and Western Medicine Diagnosis and Treatment Programs(Guidelines for the Diagnosis and Treatment of Breast Cancer with the Combination of Traditional Chinese Medicine and Western Medicine)(ZYZB-2022-798).
文摘Breast cancer is the leading cause of cancer-related deaths in women worldwide,with Hormone Receptor(HR)+being the predominant subtype.Tamoxifen(TAM)serves as the primary treatment for HR+breast cancer.However,drug resistance often leads to recurrence,underscoring the need to develop new therapies to enhance patient quality of life and reduce recurrence rates.Artemisinin(ART)has demonstrated efficacy in inhibiting the growth of drug-resistant cells,positioning art as a viable option for counteracting endocrine resistance.This study explored the interaction between artemisinin and tamoxifen through a combined approach of bioinformatics analysis and experimental validation.Five characterized genes(ar,cdkn1a,erbb2,esr1,hsp90aa1)and seven drug-disease crossover genes(cyp2e1,rorc,mapk10,glp1r,egfr,pgr,mgll)were identified using WGCNA crossover analysis.Subsequent functional enrichment analyses were conducted.Our findings confirm a significant correlation between key cluster gene expression and immune cell infiltration in tamoxifen-resistant and-sensitized patients.scRNA-seq analysis revealed high expression of key cluster genes in epithelial cells,suggesting artemisinin’s specific impact on tumor cells in estrogen receptor(ER)-positive BC tissues.Molecular target docking and in vitro experiments with artemisinin on LCC9 cells demonstrated a reversal effect in reducing migratory and drug resistance of drug-resistant cells by modulating relevant drug resistance genes.These results indicate that artemisinin could potentially reverse tamoxifen resistance in ER-positive breast cancer.
文摘目的探讨TMX基因在结直肠癌及癌旁组织中的表达是否存在差异。方法对结直肠癌的的石蜡标本及切缘组织各33例,将肿瘤组织和对应的切缘正常组织放置于同一张载玻片上,采用免疫组化方法,利用IPP6.0软件进行半定量分析,研究TMX基因在结直肠癌组织中及手术切缘的表达情况,并比较这两组是否存在表达差异。结果 TMX基因在结直肠癌组织及癌旁组织均表达,在结直肠癌组织的表达量明显低于正常切缘(0.142±0.038 VS 0.210±0.037,P<0.0001)。结论 TMX基因在结直肠癌组织的表达量显著低于正常癌旁组织,提示TMX基因可能参与结直肠癌的发病。