Objective Triple-negative breast cancer(TNBC)is the breast cancer subtype with the worst prognosis,and lacks effective therapeutic targets.Colony stimulating factors(CSFs)are cytokines that can regulate the production...Objective Triple-negative breast cancer(TNBC)is the breast cancer subtype with the worst prognosis,and lacks effective therapeutic targets.Colony stimulating factors(CSFs)are cytokines that can regulate the production of blood cells and stimulate the growth and development of immune cells,playing an important role in the malignant progression of TNBC.This article aims to construct a novel prognostic model based on the expression of colony stimulating factors-related genes(CRGs),and analyze the sensitivity of TNBC patients to immunotherapy and drug therapy.Methods We downloaded CRGs from public databases and screened for differentially expressed CRGs between normal and TNBC tissues in the TCGA-BRCA database.Through LASSO Cox regression analysis,we constructed a prognostic model and stratified TNBC patients into high-risk and low-risk groups based on the colony stimulating factors-related genes risk score(CRRS).We further analyzed the correlation between CRRS and patient prognosis,clinical features,tumor microenvironment(TME)in both high-risk and low-risk groups,and evaluated the relationship between CRRS and sensitivity to immunotherapy and drug therapy.Results We identified 842 differentially expressed CRGs in breast cancer tissues of TNBC patients and selected 13 CRGs for constructing the prognostic model.Kaplan-Meier survival curves,time-dependent receiver operating characteristic curves,and other analyses confirmed that TNBC patients with high CRRS had shorter overall survival,and the predictive ability of CRRS prognostic model was further validated using the GEO dataset.Nomogram combining clinical features confirmed that CRRS was an independent factor for the prognosis of TNBC patients.Moreover,patients in the high-risk group had lower levels of immune infiltration in the TME and were sensitive to chemotherapeutic drugs such as 5-fluorouracil,ipatasertib,and paclitaxel.Conclusion We have developed a CRRS-based prognostic model composed of 13 differentially expressed CRGs,which may serve as a useful tool for predicting the prognosis of TNBC patients and guiding clinical treatment.Moreover,the key genes within this model may represent potential molecular targets for future therapies of TNBC.展开更多
成人发病的白质脑病合并轴索球样变和色素性胶质细胞(adult-onset leukoencephalopathy with axonal spheroids and pigmented glia,ALSP)是临床罕见的常染色体显性遗传病,其具体的发病机制目前还未明确。集落刺激因子1受体(colony-stim...成人发病的白质脑病合并轴索球样变和色素性胶质细胞(adult-onset leukoencephalopathy with axonal spheroids and pigmented glia,ALSP)是临床罕见的常染色体显性遗传病,其具体的发病机制目前还未明确。集落刺激因子1受体(colony-stimulating factor 1 receptor,CSF1R)是一种细胞表面跨膜酪氨酸激酶受体,与其相关的编码基因突变已被证实是ALSP的潜在致病因素。然而,目前关于CSF1R基因突变致使ALSP发病的具体机制尚不清楚。本文回顾CSF1R基因在ALSP发病过程中的突变位点及致病机制研究,发现CSF1R突变可以通过显性负性效应、功能丧失、单倍体剂量不足及功能获得等机制导致小胶质细胞功能异常,进而引起ALSP的发病。对ALSP病因的深入认识有助于更好地探索潜在的治疗方法。展开更多
目的:探讨无外周血CD34监测下聚乙二醇重组人粒细胞集落刺激因子(PEG-rhG-CSF)在血液肿瘤自体外周血干细胞动员中的采集时机及采集效果。方法:回顾性分析2017年8月至2022年1月福建医科大学附属第一医院收治的46例行自体外周血干细胞动...目的:探讨无外周血CD34监测下聚乙二醇重组人粒细胞集落刺激因子(PEG-rhG-CSF)在血液肿瘤自体外周血干细胞动员中的采集时机及采集效果。方法:回顾性分析2017年8月至2022年1月福建医科大学附属第一医院收治的46例行自体外周血干细胞动员的血液恶性肿瘤患者。采用大剂量化疗联合PEG-rhG-CSF或重组人粒细胞集落刺激因子(G-CSF)动员方案,其中应用PEG-rhG-CSF动员的27例(PEG-rhG-CSF组),应用G-CSF动员的19例(G-CSF组),比较两组患者动员采集效果。结果:46例患者共采集86例次,PEG-rhG-CSF组与G-CSF组获得采集物的单个核细胞中位数分别为6.54(3.85-12.61)×10^(8)/kg和6.15(1.13-11.58)×10^(8)/kg(P>0.05),采集物CD34^(+)细胞数分别为11.44(1.33-65.02)×10^(6)/kg和4.95(0.30-24.02)×10^(6)/kg(P<0.05),采集时机分别为14(10-20)和14(4-22)d(P>0.05)。PEG-rhG-CSF组在外周血白细胞(WBC)≥10×10^(9)/L时单次所采集的产物CD34^(+)细胞数明显高于外周血WBC<10×10^(9)/L时采集的数量[19.04(2.85-65.02)×10^(6)/kg vs 6.22(0.81-34.86)×10^(6)/kg,(P<0.05)]。结论:采用PEG-rhG-CSF动员外周血干细胞单次采集足量CD34^(+)细胞成功率高,中位动员时间为14 d;在无外周血CD34监测情况下,外周血WBC≥10×10^(9)/L可以考虑作为单次采集足量干细胞的采集阈值。展开更多
文摘Objective Triple-negative breast cancer(TNBC)is the breast cancer subtype with the worst prognosis,and lacks effective therapeutic targets.Colony stimulating factors(CSFs)are cytokines that can regulate the production of blood cells and stimulate the growth and development of immune cells,playing an important role in the malignant progression of TNBC.This article aims to construct a novel prognostic model based on the expression of colony stimulating factors-related genes(CRGs),and analyze the sensitivity of TNBC patients to immunotherapy and drug therapy.Methods We downloaded CRGs from public databases and screened for differentially expressed CRGs between normal and TNBC tissues in the TCGA-BRCA database.Through LASSO Cox regression analysis,we constructed a prognostic model and stratified TNBC patients into high-risk and low-risk groups based on the colony stimulating factors-related genes risk score(CRRS).We further analyzed the correlation between CRRS and patient prognosis,clinical features,tumor microenvironment(TME)in both high-risk and low-risk groups,and evaluated the relationship between CRRS and sensitivity to immunotherapy and drug therapy.Results We identified 842 differentially expressed CRGs in breast cancer tissues of TNBC patients and selected 13 CRGs for constructing the prognostic model.Kaplan-Meier survival curves,time-dependent receiver operating characteristic curves,and other analyses confirmed that TNBC patients with high CRRS had shorter overall survival,and the predictive ability of CRRS prognostic model was further validated using the GEO dataset.Nomogram combining clinical features confirmed that CRRS was an independent factor for the prognosis of TNBC patients.Moreover,patients in the high-risk group had lower levels of immune infiltration in the TME and were sensitive to chemotherapeutic drugs such as 5-fluorouracil,ipatasertib,and paclitaxel.Conclusion We have developed a CRRS-based prognostic model composed of 13 differentially expressed CRGs,which may serve as a useful tool for predicting the prognosis of TNBC patients and guiding clinical treatment.Moreover,the key genes within this model may represent potential molecular targets for future therapies of TNBC.
文摘目的:探讨无外周血CD34监测下聚乙二醇重组人粒细胞集落刺激因子(PEG-rhG-CSF)在血液肿瘤自体外周血干细胞动员中的采集时机及采集效果。方法:回顾性分析2017年8月至2022年1月福建医科大学附属第一医院收治的46例行自体外周血干细胞动员的血液恶性肿瘤患者。采用大剂量化疗联合PEG-rhG-CSF或重组人粒细胞集落刺激因子(G-CSF)动员方案,其中应用PEG-rhG-CSF动员的27例(PEG-rhG-CSF组),应用G-CSF动员的19例(G-CSF组),比较两组患者动员采集效果。结果:46例患者共采集86例次,PEG-rhG-CSF组与G-CSF组获得采集物的单个核细胞中位数分别为6.54(3.85-12.61)×10^(8)/kg和6.15(1.13-11.58)×10^(8)/kg(P>0.05),采集物CD34^(+)细胞数分别为11.44(1.33-65.02)×10^(6)/kg和4.95(0.30-24.02)×10^(6)/kg(P<0.05),采集时机分别为14(10-20)和14(4-22)d(P>0.05)。PEG-rhG-CSF组在外周血白细胞(WBC)≥10×10^(9)/L时单次所采集的产物CD34^(+)细胞数明显高于外周血WBC<10×10^(9)/L时采集的数量[19.04(2.85-65.02)×10^(6)/kg vs 6.22(0.81-34.86)×10^(6)/kg,(P<0.05)]。结论:采用PEG-rhG-CSF动员外周血干细胞单次采集足量CD34^(+)细胞成功率高,中位动员时间为14 d;在无外周血CD34监测情况下,外周血WBC≥10×10^(9)/L可以考虑作为单次采集足量干细胞的采集阈值。
