Drug resistance remains a major challenge in breast cancer chemotherapy,yet the metabolic alterations underlying this phenomenon are not fully understood.There is much evidence indicating the cellular heterogeneity am...Drug resistance remains a major challenge in breast cancer chemotherapy,yet the metabolic alterations underlying this phenomenon are not fully understood.There is much evidence indicating the cellular heterogeneity among cancer cells,which exhibit varying degrees of metabolic reprogramming and thus may result in differential contributions to drug resistance.A home-built single-cell quantitative mass spectrometry(MS)platform,which integrates micromanipulation and electro-osmotic sampling,was developed to quantitatively profile the tricarboxylic acid(TCA)cycle metabolites at the single-cell level.Using this platform,the metabolic profiles of drug-sensitive MCF-7 breast cancer cells and their drug-resistant derivative MCF-7/ADR cells were compared.This results revealed a selective upregulation of downstream TCA cycle metabolites includingα-ketoglutarate,succinate,fumarate,and malate in drug-resistant cancer cells,while early TCA metabolites remained largely unchanged.Furthermore,notable variations in the abundance of the metabolites were observed in individual cells.The comparative analysis also revealed that not all MCF-7/ADR cells exhibit the same degree of metabolic deviation from the parental line in the metabolites during resistance acquisition.The observed metabolic profiles indicate enhanced glutaminolysis,altered mitochondrial electron transport chain activity,and increased metabolic flexibility in drug-resistant cancer cells that support their survival under chemotherapeutic stress.The findings further suggest the potential for incorporating cellular metabolic heterogeneity into future drug resistance studies.展开更多
目的:探讨体重指数(BMI)与肛周脓肿发病的关系及其炎症的相关机制。方法:将25例肛周脓肿手术患者列为观察组,同期25例行混合痔手术患者为对照组。收集2组患者年龄、性别、体重及身高等基本信息,并用ELISA法比较肿瘤坏死因子(TNF)-α、...目的:探讨体重指数(BMI)与肛周脓肿发病的关系及其炎症的相关机制。方法:将25例肛周脓肿手术患者列为观察组,同期25例行混合痔手术患者为对照组。收集2组患者年龄、性别、体重及身高等基本信息,并用ELISA法比较肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6及C反应蛋白(CRP)表达情况。结果:观察组BMI正常8例,超重和肥胖17例;对照组BMI正常18例,超重和肥胖7例。观察组超重和肥胖例数多于对照组,差异有统计学意义(P<0.05)。观察组CRP水平高于对照组(679.98±372.28μg/L vs 358.14±191.96μg/L,P<0.05);2组IL-6和TNF-α水平比较差异无统计学意义(P>0.05)。将所有患者按体重指数进行分组,超重和肥胖组CRP水平明显高于正常组(772.75±322.95μg/L vs 302.95±141.56μg/L,P<0.05);IL-6水平高于正常组(3.66±1.37ng/L vs 1.87±0.41ng/L,P<0.05);2组TNF-α水平比较差异无统计学意义(P>0.05)。结论:BMI与肛周脓肿的发病存在一定的相关性,其具体机制与慢性炎症有关,更高级别的证据需大样本量的临床队列研究进一步证实。展开更多
基金supported by National Natural Science Foundation of China(22374080,22174068,21722504)Primary Research&Development Plan of Jiangsu Province(BK20221303,BE2022796)+1 种基金Open Foundation of State Key Laboratory of Reproductive Medicine(SKLRM-2022BP1,JX116GSP20240507)Science and Technology Development Fund of NJMU(NJMUQY2022003)。
文摘Drug resistance remains a major challenge in breast cancer chemotherapy,yet the metabolic alterations underlying this phenomenon are not fully understood.There is much evidence indicating the cellular heterogeneity among cancer cells,which exhibit varying degrees of metabolic reprogramming and thus may result in differential contributions to drug resistance.A home-built single-cell quantitative mass spectrometry(MS)platform,which integrates micromanipulation and electro-osmotic sampling,was developed to quantitatively profile the tricarboxylic acid(TCA)cycle metabolites at the single-cell level.Using this platform,the metabolic profiles of drug-sensitive MCF-7 breast cancer cells and their drug-resistant derivative MCF-7/ADR cells were compared.This results revealed a selective upregulation of downstream TCA cycle metabolites includingα-ketoglutarate,succinate,fumarate,and malate in drug-resistant cancer cells,while early TCA metabolites remained largely unchanged.Furthermore,notable variations in the abundance of the metabolites were observed in individual cells.The comparative analysis also revealed that not all MCF-7/ADR cells exhibit the same degree of metabolic deviation from the parental line in the metabolites during resistance acquisition.The observed metabolic profiles indicate enhanced glutaminolysis,altered mitochondrial electron transport chain activity,and increased metabolic flexibility in drug-resistant cancer cells that support their survival under chemotherapeutic stress.The findings further suggest the potential for incorporating cellular metabolic heterogeneity into future drug resistance studies.
文摘目的:探讨体重指数(BMI)与肛周脓肿发病的关系及其炎症的相关机制。方法:将25例肛周脓肿手术患者列为观察组,同期25例行混合痔手术患者为对照组。收集2组患者年龄、性别、体重及身高等基本信息,并用ELISA法比较肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6及C反应蛋白(CRP)表达情况。结果:观察组BMI正常8例,超重和肥胖17例;对照组BMI正常18例,超重和肥胖7例。观察组超重和肥胖例数多于对照组,差异有统计学意义(P<0.05)。观察组CRP水平高于对照组(679.98±372.28μg/L vs 358.14±191.96μg/L,P<0.05);2组IL-6和TNF-α水平比较差异无统计学意义(P>0.05)。将所有患者按体重指数进行分组,超重和肥胖组CRP水平明显高于正常组(772.75±322.95μg/L vs 302.95±141.56μg/L,P<0.05);IL-6水平高于正常组(3.66±1.37ng/L vs 1.87±0.41ng/L,P<0.05);2组TNF-α水平比较差异无统计学意义(P>0.05)。结论:BMI与肛周脓肿的发病存在一定的相关性,其具体机制与慢性炎症有关,更高级别的证据需大样本量的临床队列研究进一步证实。
