搜索到742篇“ RADIORESISTANCE“的相关文章
LncRNA HOTAIR promotes DNA damage repair and radioresistance by targeting ATR in colorectal cancer
2024年
Long non-coding RNAs(lncRNAs)have been implicated in cancer progression and drug resistance development.Moreover,there is evidence that lncRNA HOX transcript antisense intergenic RNA(HOTAIR)is involved in colorectal cancer(CRC)progression.The present study aimed to examine the functional role of lncRNA HOTAIR in conferring radiotherapy resistance in CRC cells,as well as the underlying mechanism.The relative expression levels of HOTAIR were examined in 70 pairs of CRC tumor and para-cancerous tissues,as well as in radiosensitive and radioresistant samples.The correlations between HOTAIR expression levels and clinical features of patients with CRC were assessed using the Chi-square test.Functional assays such as cell proliferation,colony formation and apoptosis assays were conducted to determine the radiosensitivity in CRC cells with HOTAIR silencing after treatment with different doses of radiation.RNA pull-down assay andfluorescence in situ hybridization(FISH)were used to determine the interaction between HOTAIR and DNA damage response mediator ataxia-telangiectasia mutated-and Rad3-related(ATR).HOTAIR was significantly upregulated in CRC tumor tissues,especially in radioresistant tumor samples.The elevated expression of HOTAIR was correlated with more advanced histological grades,distance metastasis and the poor prognosis in patients with CRC.Silencing HOTAIR suppressed the proliferation and promoted apoptosis and radiosensitivity in CRC cells.HOTAIR knockdown also inhibited the tumorigenesis of CRC cells and enhanced the sensitivity to radiotherapy in a mouse xenograft model.Moreover,the data showed that HOTAIR could interact with ATR to regulate the DNA damage repair signaling pathway.Silencing HOTAIR impaired the ATR-ATR interacting protein(ATRIP)complex and signaling in cell cycle progression.Collectively,the present results indicate that lncRNA HOTAIR facilitates the DNA damage response pathway and promotes radioresistance in CRC cells by targeting ATR.
HAIQING HUHAO YANGSHUAISHUAI FANXUE JIAYING ZHAOHONGRUI LI
关键词:CRCRADIORESISTANCEATR
Role of glioma stem cells in promoting tumor chemo- and radioresistance: A systematic review of potential targeted treatments
2024年
BACKGROUND Gliomas pose a significant challenge to effective treatment despite advancements in chemotherapy and radiotherapy.Glioma stem cells(GSCs),a subset within tumors,contribute to resistance,tumor heterogeneity,and plasticity.Recent studies reveal GSCs’role in therapeutic resistance,driven by DNA repair mechanisms and dynamic transitions between cellular states.Resistance mechanisms can involve different cellular pathways,most of which have been recently reported in the literature.Despite progress,targeted therapeutic approaches lack consensus due to GSCs’high plasticity.AIM To analyze targeted therapies against GSC-mediated resistance to radio-and chemotherapy in gliomas,focusing on underlying mechanisms.METHODS A systematic search was conducted across major medical databases(PubMed,Embase,and Cochrane Library)up to September 30,2023.The search strategy utilized relevant Medical Subject Heading terms and keywords related to including“glioma stem cells”,“radiotherapy”,“chemotherapy”,“resistance”,and“targeted therapies”.Studies included in this review were publications focusing on targeted therapies against the molecular mechanism of GSC-mediated re-sistance to radiotherapy resistance(RTR).RESULTS In a comprehensive review of 66 studies on stem cell therapies for SCI,452 papers were initially identified,with 203 chosen for full-text analysis.Among them,201 were deemed eligible after excluding 168 for various reasons.The temporal breakdown of studies illustrates this trend:2005-2010(33.3%),2011-2015(36.4%),and 2016-2022(30.3%).Key GSC models,particularly U87(33.3%),U251(15.2%),and T98G(15.2%),emerge as significant in research,reflecting their representativeness of glioma characteristics.Pathway analysis indicates a focus on phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin(mTOR)(27.3%)and Notch(12.1%)pathways,suggesting their crucial roles in resistance development.Targeted molecules with mTOR(18.2%),CHK1/2(15.2%),and ATP binding cassette G2(12.1%)as frequent tar
Edoardo AgostiMarco ZeppieriMattia GhidoniTamara IusAlessandro TelMarco Maria FontanellaPier Paolo Panciani
关键词:CHEMORESISTANCERADIORESISTANCE
Two distinct subpopulations of marginal zone B cells exhibit differential antibody-producing capacities and radioresistance被引量:1
2024年
Marginal zone(MZ)B cells,which are splenic innate-like B cells that rapidly secrete antibodies(Abs)against blood-borne pathogens,are composed of heterogeneous subpopulations.Here,we showed that MZ B cells can be divided into two distinct subpopulations according to their CD80 expression levels.CD80^(high)MZ B cells exhibited greater Ab-producing,proliferative,and IL-10-secreting capacities than did CD80^(low)MZ B cells.Notably,CD80^(high)MZ B cells survived 2-Gy whole-body irradiation,whereas CD80^(low)MZ B cells were depleted by irradiation and then repleted with one month after irradiation.Depletion of CD80^(low)MZ B cells led to accelerated development of type II collagen(CII)-induced arthritis upon immunization with bovine CII.CD80^(high)MZ B cells exhibited higher expression of genes involved in proliferation,plasma cell differentiation,and the antioxidant response.CD80^(high)MZ B cells expressed more autoreactive B cell receptors(BCRs)that recognized double-stranded DNA or CII,expressed more immunoglobulin heavy chain sequences with shorter complementarity-determining region 3 sequences,and included more clonotypes with no N-nucleotides or with B-1a BCR sequences than CD80^(low)MZ B cells.Adoptive transfer experiments showed that CD21^(+)CD23^(+)transitional 2 MZ precursors preferentially generated CD80^(low)MZ B cells and that a proportion of CD80^(low)MZ B cells were converted into CD80^(high)MZ B cells;in contrast,CD80^(high)MZ B cells stably remained CD80^(high)MZ B cells.In summary,MZ B cells can be divided into two subpopulations according to their CD80 expression levels,Ab-producing capacity,radioresistance,and autoreactivity,and these findings may suggest a hierarchical composition of MZ B cells with differential stability and BCR specificity.
Sujin LeeYeunjung KoHyun Woo LeeWon Joon OhHun Gi HongDinuka AriyaratneSe Jin ImTae Jin Kim
关键词:CD80AUTOREACTIVITYRADIORESISTANCE
Regulator of G protein signaling 20 contributes to radioresistance of non-small cell lung cancer cells by suppressing pyroptosis
2024年
Objective:To investigate the potential role of the regulator of G protein signaling 20(RGS20)in radioresistance of non-small cell lung cancer(NSCLC).Methods:A total of 35 lung adenocarcinoma(LUAD)patients from The Cancer Genome Atlas(TCGA),who un-derwent radiotherapy,were enrolled and divided into radiosensitive(n=16)and radioresistant(n=19)groups based on clinical prognosis.The expression and prognosis of RGS20 were analyzed by Gene Expression Profiling Interactive Analysis(GEPIA)database.A radioresistant cell line(A549R)was constructed by irradiating A549 cells with 6 Gy X-rays for 10 fractions.Cell survival was measured by colony formation assay.The regulatory effect of RGS20 on pyroptosis were verified by LDH release and Western blot assay,and the underlying mech-anism was investigated by transfecting RGS20 siRNA and applying a GSDMD inhibitor.Results:A total of 2,181 differentially expressed genes(DEGs)were identified by analyzing the data of radio-sensitive and radioresistant individuals from the TCGA-LUAD dataset.These DEGs were enriched in G alpha(z)signalling events analyzed by Reactome database.RGS20 exhibited significant upregulation among the DEGs,and its higher expression predicted poor prognosis in LUAD patients.In vitro,the expression of RGS20 protein was increased by irradiation in A549 cells,whereas it remained at much high levels in A549R cells regardless of irradiation.After irradiation,the expressions of pyroptosis-related proteins were significantly increased in A549 cells(P<0.05),with no significant changes were observed in A549R cells.Treatment with LDC7559 significantly reduced LDH release(P<0.01)and improved the survival rate of irradiated A549 cells(P<0.01).Furthermore,knockdown of RGS20 gene in A549R cells significantly increased LDH release(P<0.001)and enhanced radiosensitivity(P<0.01),while LDC7559 administration reversed LDH release(P<0.01)and radiation-induced cell death increased by siRGS20(P<0.05).Meantime,the increased expression level of GSDMD-NT was observed in A549 and A549R c
Jialing ZhangZhaoyan JiangXinglong LiuXiaoya JinYan PanYang BaiJianghong ZhangChunlin Shao
关键词:NSCLCRADIORESISTANCEPYROPTOSIS
Engineering biomimetic nanosystem targeting multiple tumor radioresistance hallmarks for enhanced radiotherapy
2024年
Tumor cells establish a robust self-defense system characterized by hypoxia,antioxidant overexpression,DNA damage repair,and so forth to resist radiotherapy.Targeting one of these features is insufficient to overcome radioresistance due to the feedback mechanisms initiated by tumor cells under radiotherapy.Therefore,we herein developed an engineering biomimetic nanosystem(M@HHPt)masked with tumor cell membranes and loaded with a hybridized protein-based nanoparticle carrying oxygens(O_(2))and cisplatin prodrugs(Pt(Ⅳ))to target multiple tumor radioresistance hallmarks for enhanced radiotherapy.After administration,M@HHPt actively targeted and smoothly accumulated in tumor cells by virtue of its innate homing abilities to realize efficient co-delivery of O_(2)and Pt(Ⅳ).O_(2)introduction induced hypoxia alleviation cooperated with Pt(Ⅳ)reduction caused glutathione consumption greatly amplified radiotherapy-ignited cellular oxidative stress.Moreover,the released cisplatin effectively hindered DNA damage repair by crosslinking with radiotherapy-produced DNA fragments.Consequently,M@HHPt-sensitized radiotherapy significantly suppressed the proliferation of lung cancer H1975 cells with an extremely high sensitizer enhancement ratio of 1.91 and the progression of H1975 tumor models with an excellent tumor inhibition rate of 94.7%.Overall,this work provided a feasible strategy for tumor radiosensitization by overcoming multiple radioresistance mechanisms.
Shuxiang WangHongmei CaoCui-Cui ZhaoQian WangDianyu WangJinjian LiuLijun YangJianfeng Liu
关键词:RADIOSENSITIZATION
调控线粒体质量逆转肺癌放疗抵抗的研究进展
2024年
放射治疗是肺癌临床综合治疗的重要手段之一,但其在肺癌根治中仍存在很多困难和挑战,如何克服肺癌放疗抵抗和增强放疗后的免疫效应是亟待解决的科学问题。线粒体是调控肿瘤发生、发展以及治疗效果的重要细胞器,线粒体质量控制与肺癌放疗抵抗密切相关。本文从线粒体代谢、线粒体分子伴侣调控、线粒体动力学及自噬、线粒体内氧化还原水平和线粒体介导细胞凋亡方面综述了线粒体质量控制在肺癌放疗抵抗以及逆转抵抗过程中的作用机制,以期为肺癌放疗联合免疫治疗的方案提供参考。
雷旭丹黄宇君黄灵潇徐珍妮刘登群
关键词:肺癌线粒体
TRIP13通过同源重组通路提高肺腺癌细胞的放射抗性
2024年
背景与目的放疗是非小细胞肺癌(non-small cell lung cancer,NSCLC)最常用的治疗手段之一。然而,一部分肿瘤细胞对放射线的不敏感是放疗疗效差、患者预后不良的重要原因之一,探究放射抵抗背后的深层机制是解决这一临床难题的关键。本研究旨在寻找与肺腺癌(lungadenocarcinoma,LUAD)放射抵抗相关的分子,初步经数据库筛选锁定甲状腺素受体结合因子13(thyroid hormone receptor interactor 13,TRIP13)为主要研究对象,并探索TRIP13是否与LUAD的放射抵抗有关及具体机制,以期为临床接受放疗的LUAD患者的联合治疗提供理论依据和潜在靶点。方法选取基因表达综合数据库(Gene Expression Omnibus,GEO)中的GSE18842、GSE19188和GSE33532共3个数据集,借助R 4.1.3软件分别筛选3个数据集中差异表达的基因(|logFC|>1.5,P<0.05),之后使用Venn diagram找出在3个数据集中共有的差异表达基因。随后,借助STRING在线工具和Cytoscape软件,对筛选出来的差异基因进行蛋白质相互作用分析和模块分析,借助Kaplan-Meier Plotter数据库对各基因进行生存预后分析,并确定TRIP13基因作为后续主要研究分子。随后,采用亚致死性剂量照射法对人LUAD细胞系H292进行多次X射线照射,以构建具有放射抗性的细胞系H292DR。采用细胞计数试剂盒-8(cell counting kit-8,CCK-8)实验和克隆形成实验验证H292DR细胞的放射抗性能力。Western blot检测H292细胞和H292DR细胞中TRIP13蛋白的表达水平。使用小干扰RNA(small interfering RNA,siRNA)沉默H292DR细胞中TRIP 13蛋白的表达并进行Western blot检测。观察TRIP13沉默后H292DR细胞的克隆形成能力和迁移能力,随后检测共济失调-毛细血管扩张突变(ataxia telangiectasia mutated,ATM)蛋白等与同源重组密切相关的蛋白的表达水平变化。结果经多个GEO数据集筛选、外部数据集的验证以及生存分析发现,TRIP13在LUAD中高表达,并与接受过放疗的LUAD患者的�
葛舒童谷润川杨雄涛许长丹王诗杰朱广迎
关键词:肺肿瘤同源重组
YWHAZ gene contributes to the radioresistance of oral squamous cell carcinoma cells
2024年
Objective:To investigate the contribution of YWHAZ gene on the radioresistance and metastasis ability of oral squamous cell carcinoma(OSCC)cells.Mathods:The relationship between the expression level of YWHAZ gene and the survival of head and neck squamous cell carcinoma(HNSC)patients was analyzed using Gene Expression Profiling Interactive Analysis(GEPIA)database.A radioresistance cell line(CAL-27R)was constructed by irradiating CAL-27 cells with frac-tional doses.Cell survival was measured by colony formation assay.Cell migration and invasion were detected by transwell assay.The formation of yH2AX foci was detected by immunofluorescence assay,The protein expressions were detected by Westemn blot assay.In some experiments,CAL-27R cells were effectively transferred with siRNA YWHAZ(siYWHAZ).Results:GEPIA database showed that the expression level of YWHAZ in HNSC tumors was higher than that in adjacent normal tissues,and the HNSC patients with higher level of YWHAZ had a shorter survival.In vitro experiments demonstrated that the expression of YWHAZ protein in CAL-27 cells was lower than HSC-3 cells(t=18.89,P<0.01)and radioresistant CAL-27R cells(t=25.70,P<0.01).Knockdown of YWHAZ gene significantly increased radiation-induced cell killing effect,apoptosis induction,and yH2AX foci formation inCAL-27R and HSC-3 cells.Moreover,siRNA YWHAZ transfection also reduced the invasion and migration abilities of the irradiated CAL 27R[t=21.09,P<0.01(migration);t=6.16,P<0.05(invasion)]and HSC-3 cells[t=34.53,P<0.001(migration);t=4.92,P<0.05(invasion)]and attenuated radiation-induced expressions of metastasis-related proteins,Conclusion:YWHAZ contributes to the radioresistance of oral squamous cells and thus it may applicable to be a potential target for OSOC radiotherapy.
Songling HuCong ChenHengheng ChenXin YuXiaofei LiYang BaiChunlin Shao
八聚体结合转录因子4通过调节上皮-间质转化促进食管鳞状细胞癌进展和放疗抵抗
2024年
目的探讨八聚体结合转录因子4(Oct4)与食管鳞状细胞癌进展和放疗抵抗的具体作用和分子机制。方法利用基因表达谱数据动态分析(GEPIA)数据库,分析Oct4基因在不同类型肿瘤组织和对应癌旁正常组织中的表达差异。2013年1月至2022年5月在河南省胸科医院接受手术联合放疗治疗的196例食管鳞状细胞癌患者,收集其临床资料及手术切除组织标本,采用免疫组化法检测癌及癌旁组织中Oct4蛋白的表达。通过慢病毒包装系统构建上调和下调Oct4的食管鳞状细胞癌细胞系,采用细胞计数试剂盒8法检测细胞增殖能力,划痕实验检测细胞迁移能力,克隆形成实验检测细胞的放疗敏感性,免疫荧光实验检测DNA损伤水平,Western blot检测Oct4、人磷酸化组蛋白(γ-H2AX)、E-cadherin、N-cadherin、vimentin、锌指E盒结合同源盒1(ZEB1)的表达。结果GEPIA数据库资料分析显示,食管癌组织中Oct4 mRNA的表达水平高于其癌旁组织(P<0.05)。196例食管鳞状细胞癌患者的肿瘤组织中Oct4蛋白表达水平为78.35±1.42,高于癌旁组织(16.27±0.49,P<0.001)。Oct4高表达组患者的生存时间明显短于Oct4低表达组(中位生存时间分别为25.40和47.00个月;HR=1.68,P=0.022)。与对照组比较,Oct4上调组KYSE510细胞增殖能力增强(培养72 h,吸光度分别为1.73±0.19和1.35±0.10,P=0.007),迁移能力增强[培养24 h,细胞迁移率分别为(41.67±1.20)%和(23.67±1.86)%,P=0.001],放疗敏感性降低(辐射增敏比分别为0.69±0.06和1.00±0.02,P=0.010),放疗后γ-H2AX表达水平降低,ZEB1、vimentin和N-cadherin表达升高,E-cadherin表达下降;Oct4下调1组和Oct4下调2组KYSE150细胞增殖能力减弱(培养72 h,吸光度分别为2.51±0.17、2.38±0.16和3.33±0.07,均P<0.01),迁移能力下降[培养24 h,细胞迁移率分别为(13.33±0.88)%、(13.00±1.00)%和(40.33±2.03)%,均P<0.001],放疗敏感性增强(辐射增敏比分别为1.34±0.11、1.24±0.07和1.00±0.02,均P<0.05),放疗
张静祁敏现李怡晓李雪冰张光照柴雅玫
关键词:食管鳞状细胞癌DNA损伤修复上皮-间质转化肿瘤进展
放疗诱导ZBTB7A基因过表达在胶质母细胞瘤放疗抵抗中的作用被引量:1
2024年
目的 应用大样本临床测序数据联合体外细胞筛选放疗抵抗相关基因,探讨放疗诱导含锌指和BTB结构域蛋白质7A(ZBTB7A)过表达在胶质母细胞瘤(GBM)放疗抵抗中的作用.方法 纳入中国脑胶质瘤基因组图谱计划数据库中966例脑胶质瘤标本的测序和临床数据筛选及验证GBM放疗抵抗候选基因:(1)纳入226例原发GBM(pGBM)与134例手术+放疗后复发的GBM(rGBM)非配对肿瘤标本,以及15例首次诊断为pGBM、手术+放疗后复发再次行手术切除的配对肿瘤标本的测序数据筛选GBM放疗抵抗候选基因,并验证ZBTB7A是否为放疗抵抗相关基因;(2)比较异柠檬酸脱氢酶(IDH)野生型与突变型胶质瘤标本ZBTB7A mRNA表达量的差异(数据集1样本量分别为286、356例,数据集2分别为149、175例);(3)比较ZBTB7A高表达组(148例)与低表达组(148例)GBM患者生存期的差异.纳入2019年4月至2022年12月于首都医科大学附属北京天坛医院手术并经病理学诊断的pGBM与rGBM肿瘤标本(各12例),采用免疫组织化学染色法检测两组肿瘤组织中ZBTB7A蛋白表达水平的差异.采用高能X线照射人脑GBM细胞株U87、LN229和U251(单次13 Gy,照射6.5 min),4、8 h后采用定量PCR方法检测细胞ZBTB7A mRNA的表达量;照射U87和LN229细胞(单次5 Gy,照射2.5 min),1、2、4、8、12 h后采用蛋白质免疫印迹法检测ZBTB7A蛋白 及DNA损伤标志物H2AX蛋白的表达量.采用小干扰RNA慢病毒(shRNA)感染法敲低U87细胞ZBTB7A的表达后,采用高能X线照射(单次照射剂量为5 Gy,照射2.5 min),1 h后行彗星实验检测细胞的DNA损伤情况;采用平板克隆实验检测细胞的增殖情况.结果 非配对和配对肿瘤标本测序数据交叉筛选显示,rGBM组ZBTB7A mRNA的表达量均高于pGBM组(均P<0.05).IDH野生型ZBTB7A mRNA表达量高于IDH突变型;ZBTB7A高表达GBM患者的生存期短于低表达者;免疫组织化学染色证实ZBTB7A蛋白在rGBM肿瘤标本中的表达量高于pGBM,上述数据�
冯瑾高德志王鹏邱晓光刘彦伟
关键词:胶质母细胞瘤过表达

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