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C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 pathway as a therapeutic target and regulatory mechanism for spinal cord injury
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作者 Xiangzi Wang Xiaofei Niu +4 位作者 Yingkai Wang Yang Liu Cheng Yang Xuyi Chen Zhongquan Qi 《Neural Regeneration Research》 SCIE CAS 2025年第8期2231-2244,共14页
Spinal cord injury involves non-reversible damage to the central nervous system that is characterized by limited regenerative capacity and secondary inflammatory damage.The expression of the C-C motif chemokine ligand... Spinal cord injury involves non-reversible damage to the central nervous system that is characterized by limited regenerative capacity and secondary inflammatory damage.The expression of the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis exhibits significant differences before and after injury.Recent studies have revealed that the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis is closely associated with secondary inflammatory responses and the recruitment of immune cells following spinal cord injury,suggesting that this axis is a novel target and regulatory control point for treatment.This review comprehensively examines the therapeutic strategies targeting the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis,along with the regenerative and repair mechanisms linking the axis to spinal cord injury.Additionally,we summarize the upstream and downstream inflammatory signaling pathways associated with spinal cord injury and the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis.This review primarily elaborates on therapeutic strategies that target the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis and the latest progress of research on antagonistic drugs,along with the approaches used to exploit new therapeutic targets within the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis and the development of targeted drugs.Nevertheless,there are presently no clinical studies relating to spinal cord injury that are focusing on the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis.This review aims to provide new ideas and therapeutic strategies for the future treatment of spinal cord injury. 展开更多
关键词 apoptosis C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 pathway C-C motif chemokine receptor 2 antagonists chemokine ligand 2 chemokine receptor 2 inflammation macrophage microglia spinal cord injury therapeutic method
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P2Y1 receptor in Alzheimer’s disease
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作者 Shan Luo Yifei Wang Tatsuhiro Hisatsune 《Neural Regeneration Research》 SCIE CAS 2025年第2期440-453,共14页
Alzheimer’s disease is the most frequent form of dementia characterized by the deposition of amyloid-beta plaques and neurofibrillary tangles consisting of hyperphosphorylated tau.Targeting amyloid-beta plaques has b... Alzheimer’s disease is the most frequent form of dementia characterized by the deposition of amyloid-beta plaques and neurofibrillary tangles consisting of hyperphosphorylated tau.Targeting amyloid-beta plaques has been a primary direction for developing Alzheimer’s disease treatments in the last decades.However,existing drugs targeting amyloid-beta plaques have not fully yielded the expected results in the clinic,necessitating the exploration of alternative therapeutic strategies.Increasing evidence unravels that astrocyte morphology and function alter in the brain of Alzheimer’s disease patients,with dysregulated astrocytic purinergic receptors,particularly the P2Y1 receptor,all of which constitute the pathophysiology of Alzheimer’s disease.These receptors are not only crucial for maintaining normal astrocyte function but are also highly implicated in neuroinflammation in Alzheimer’s disease.This review delves into recent insights into the association between P2Y1 receptor and Alzheimer’s disease to underscore the potential neuroprotective role of P2Y1 receptor in Alzheimer’s disease by mitigating neuroinflammation,thus offering promising avenues for developing drugs for Alzheimer’s disease and potentially contributing to the development of more effective treatments. 展开更多
关键词 ASTROCYTES NEUROINFLAMMATION P2Y1 receptor purinergic receptor
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Role of triggering receptor expressed on myeloid cells 1/2 in secondary injury after cerebral hemorrhage
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作者 Fan Yi Hao Wu Hai-Kang Zhao 《World Journal of Clinical Cases》 SCIE 2025年第9期1-12,共12页
Intracerebral hemorrhage(ICH)is a common severe emergency in neurosurgery,causing tremendous economic pressure on families and society and devastating effects on patients both physically and psychologically,especially... Intracerebral hemorrhage(ICH)is a common severe emergency in neurosurgery,causing tremendous economic pressure on families and society and devastating effects on patients both physically and psychologically,especially among patients with poor functional outcomes.ICH is often accompanied by decreased consciousness and limb dysfunction.This seriously affects patients’ability to live independently.Although rapid advances in neurosurgery have greatly improved patient survival,there remains insufficient evidence that surgical treatment significantly improves long-term outcomes.With in-depth pathophysiological studies after ICH,increasing evidence has shown that secondary injury after ICH is related to long-term prognosis and that the key to secondary injury is various immune-mediated neuroinflammatory reactions after ICH.In basic and clinical studies of various systemic inflammatory diseases,triggering receptor expressed on myeloid cells 1/2(TREM-1/2),and the TREM receptor family is closely related to the inflammatory response.Various inflammatory diseases can be upregulated and downregulated through receptor intervention.How the TREM receptor functions after ICH,the types of results from intervention,and whether the outcomes can improve secondary brain injury and the long-term prognosis of patients are unknown.An analysis of relevant research results from basic and clinical trials revealed that the inhibition of TREM-1 and the activation of TREM-2 can alleviate the neuroinflammatory immune response,significantly improve the long-term prognosis of neurological function in patients with cerebral hemorrhage,and thus improve the ability of patients to live independently. 展开更多
关键词 Cerebral hemorrhage Secondary injury Triggering receptor expressed on myeloid cells 1/2 NEUROSURGERY Inflammatory response
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Colony-stimulating factor 3 and its receptor promote leukocyte immunoglobulin-like receptor B2 expression and ligands in gastric
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作者 Long Wang Qi Wu +7 位作者 Zong-Wen Zhang Hui Zhang Hui Jin Xin-Liang Zhou Jia-Yin Liu Dan Li Yan Liu Zhi-Song Fan 《World Journal of Gastrointestinal Oncology》 2025年第2期198-210,共13页
BACKGROUND Colony-stimulating factor 3(CSF3)and its receptor(CSF3R)are known to promote gastric cancer(GC)growth and metastasis.However,their effects on the immune microenvironment remain unclear.Our analysis indicate... BACKGROUND Colony-stimulating factor 3(CSF3)and its receptor(CSF3R)are known to promote gastric cancer(GC)growth and metastasis.However,their effects on the immune microenvironment remain unclear.Our analysis indicated a potential link between CSF3R expression and the immunosuppressive receptor leukocyte immunoglobulin-like receptor B2(LILRB2)in GC.We hypothesized that CSF3/CSF3R may regulate LILRB2 and its ligands,angiopoietin-like protein 2(ANGPTL2)and human leukocyte antigen-G(HLA-G),contributing to immunosuppression.AIM To investigate the relationship between CSF3/CSF3R and LILRB2,as well as its ligands ANGPTL2 and HLA-G,in GC.METHODS Transcriptome sequencing data from The Cancer Genome Atlas were analyzed,stratifying patients by CSF3R expression.Differentially expressed genes and immune checkpoints were evaluated.Immunohistochemistry(IHC)was performed on GC tissues.Correlation analyses of CSF3R,LILRB2,ANGPTL2,and HLA-G were conducted using The Cancer Genome Atlas data and IHC results.GC cells were treated with CSF3,and expression levels of LILRB2,ANGPTL2,and HLA-G were measured by quantitative reverse transcriptase-polymerase chain reaction and western blotting.RESULTS Among 122 upregulated genes in high CSF3R expression groups,LILRB2 showed the most significant increase.IHC results indicated high expression of LILRB2(63.0%),ANGPTL2(56.5%),and HLA-G(73.9%)in GC tissues.Strong positive correlations existed between CSF3R and LILRB2,ANGPTL2,and HLA-G mRNA levels(P<0.001).IHC confirmed positive correlations between CSF3R and LILRB2(P<0.001),and HLA-G(P=0.010),but not ANGPTL2(P>0.05).CSF3 increased LILRB2,ANGPTL2,and HLA-G expression in GC cells.Heterogeneous nuclear ribonucleoprotein H1 modulation significantly altered their expression,impacting CSF3’s regulatory effects.CONCLUSION The CSF3/CSF3R pathway may contribute to immunosuppression in GC by upregulating LILRB2 and its ligands,with heterogeneous nuclear ribonucleoprotein H1 playing a regulatory role. 展开更多
关键词 Gastric cancer Immunosuppressive receptor Colony-stimulating factor 3 Colony-stimulating factor 3 receptor Leukocyte immunoglobulin-like receptor B2 Angiopoietin-like protein 2 Human leukocyte antigen-G Heterogeneous nuclear ribonucleoprotein H1
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Efficacy of sodium-glucose cotransporter-2 inhibitors and glucagonlike peptide-1 receptor agonists on proteinuria and weight in a diabetes cohort
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作者 Di-Fei Lu Rui Zheng +1 位作者 Ang Li Jun-Qing Zhang 《World Journal of Diabetes》 2025年第2期123-132,共10页
BACKGROUND With accumulating evidence showing a benefit in the renal and cardiovascular systems,diabetes guidelines recommend that patients with diabetes and chronic kidney disease(CKD)be treated with sodium-glucose c... BACKGROUND With accumulating evidence showing a benefit in the renal and cardiovascular systems,diabetes guidelines recommend that patients with diabetes and chronic kidney disease(CKD)be treated with sodium-glucose cotransporter-2 inhibitor(SGLT2i)and/or glucagon like peptide-1 receptor agonists(GLP-1RAs)for renal protection.The real-world efficacy of the two medications on the urinary albumin-creatinine ratio(UACR)and estimated glomerular filtration rate(eGFR)remains to be explored.AIM To evaluate the SGLT2i and GLP-1RA application rates and UACR alterations after intervention in a real-world cohort of patients with diabetes.METHODS A cohort of 5482 patients with type 2 diabetes were enrolled and followed up at the Integrated Care Clinic for Diabetes of Peking University First Hospital for at least 6 months.Propensity score matching was performed,and patients who were not recommended for GLP-1RA or SGLT2i with comparable sex categories and ages were assigned to the control group at a 1:2 ratio.Blood glucose,body weight,UACR and eGFR were evaluated after 6 months of treatment in real-world clinical practice.RESULTS A total of 139(2.54%)patients started GLP-1RA,and 387(7.06%)received SGLT2i.After 6 months,the variations in fasting blood glucose,prandial blood glucose,and glycosylated hemoglobin between the GLP-1RA group and the SGLT2i and control groups were not significantly different.UACR showed a tendency toward a greater reduction compared with the control group,although this difference was not statistically significant(GLP-1RA vs control,-2.20 vs 30.16 mg/g,P=0.812;SGLT2i vs control,-20.61 vs 12.01 mg/g,P=0.327);eGFR alteration also showed no significant differences.Significant weight loss was observed in the GLP-1RA group compared with the control group(GLP-1RA vs control,-0.90 vs 0.27 kg,P<0.001),as well as in the SGLT2i group(SGLT2i vs control,-0.59 vs-0.03 kg,P=0.010).CONCLUSION Compared with patients who received other glucose-lowering drugs,patients receiving SGLT2i or GLP-1RAs presented significant weight loss,a decreasing trend in UACR and comparable glucose-lowering effects in realworld settings. 展开更多
关键词 Type 2 diabetes Chronic kidney disease Body weight Sodium-glucose cotransporter-2 inhibitors Glucagon-like peptide-1 receptor agonists
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次苷酸查尔酮对LPS诱导的RAW264.7细胞iNOS和COX-2表达的影响 被引量:1
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作者 王萌 高盼微 +4 位作者 罗子娟 常惠琳 张玥 袁庆 柴丽娟 《中国药理学通报》 CAS CSCD 北大核心 2024年第2期397-399,共3页
补骨脂为豆科植物补骨脂(Psoraleacorylifolia L.)果实,具有温肾助阳、温脾止泻的功效[1],临床上被用于治疗皮肤病、肾炎、骨折等[2-3]。次苷酸查尔酮(corylifol A,CYA)是中药补骨脂的活性成分之一,是一种异黄酮类化合物,具有抗炎、抗... 补骨脂为豆科植物补骨脂(Psoraleacorylifolia L.)果实,具有温肾助阳、温脾止泻的功效[1],临床上被用于治疗皮肤病、肾炎、骨折等[2-3]。次苷酸查尔酮(corylifol A,CYA)是中药补骨脂的活性成分之一,是一种异黄酮类化合物,具有抗炎、抗菌、抗氧化、抗骨质疏松的特性[4-5]。有研究表明,CYA能明显抑制破骨细胞的分化,且能明显降低LPS诱导的巨噬细胞一氧化氮(NO)的生成[6-7]。 展开更多
关键词 次苷酸查尔酮 RAW264.7 脂多糖 INOS cox-2 NO
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黑逍遥散调控p38MAPK/ATF2/COX-2信号通路对阿尔茨海默病大鼠神经炎症的影响 被引量:3
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作者 米彩云 彭超 +2 位作者 周君 李明成 王虎平 《中成药》 CAS CSCD 北大核心 2024年第2期590-595,共6页
目的 观察黑逍遥散对Aβ_(1-42)所致阿尔茨海默病(AD)大鼠学习记忆能力的影响,并从p38MAPK/ATF2/COX-2信号通路介导的炎症级联反应探讨其作用机制。方法 双侧海马注射1μL Aβ_(1-42)溶液复刻AD大鼠模型。筛选造模成功的大鼠50只,随机... 目的 观察黑逍遥散对Aβ_(1-42)所致阿尔茨海默病(AD)大鼠学习记忆能力的影响,并从p38MAPK/ATF2/COX-2信号通路介导的炎症级联反应探讨其作用机制。方法 双侧海马注射1μL Aβ_(1-42)溶液复刻AD大鼠模型。筛选造模成功的大鼠50只,随机分为模型组、盐酸多奈哌齐组(0.5 mg/kg)和黑逍遥散低、中、高剂量组(4.25、8.5、17 g/kg),连续给药42 d。Morris水迷宫实验检测定位航行与空间探索能力,HE染色观察海马神经元病理结构改变,ELISA法检测海马组织Aβ_(1-42)、iNOS、PGE_(2)表达,RT-qPCR法检测海马组织p38、ATF2、COX-2 mRNA表达,Western blot法检测海马组织p-p38、p-ATF2、COX-2蛋白表达。结果 与模型组比较,黑逍遥散中、高剂量组和盐酸多奈哌齐组逃避潜伏期缩短(P<0.01),有效区域运动距离、目标象限滞留时间百分比增加(P<0.01),海马CA1区神经元排列有序,胞体清晰,凋亡细胞减少,海马组织Aβ_(1-42)、iNOS、PGE_(2)水平降低(P<0.05,P<0.01),p38、COX-2 mRNA表达降低(P<0.05,P<0.01),p38、p-p38、p-ATF2、COX-2蛋白表达降低(P<0.01)。结论 黑逍遥散可改善Aβ_(1-42)所致AD大鼠的认知能力,其机制可能与阻断p38MAPK/ATF2/COX-2信号通路传导,进而减轻炎症反应有关。 展开更多
关键词 黑逍遥散 阿尔茨海默病 神经炎症 p38MAPK/ATF2/cox-2信号通路
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lncRNA-BBOX1-2通过调控成纤维细胞生长因子受体1促进胃癌的发生和发展
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作者 孙颖 顾玮 +1 位作者 王吉 郑雄 《安徽医药》 CAS 2025年第1期57-62,I0002,共7页
目的探讨长链非编码RNA(long non-coding RNA,lncRNA)BBOX1-2通过调控成纤维细胞生长因子受体1(fibroblast growth factor receptor 1,FGFR1)对胃癌的发生发展机制的影响。方法回顾性选取2017年4月至2019年1月于上海交通大学医学院附属... 目的探讨长链非编码RNA(long non-coding RNA,lncRNA)BBOX1-2通过调控成纤维细胞生长因子受体1(fibroblast growth factor receptor 1,FGFR1)对胃癌的发生发展机制的影响。方法回顾性选取2017年4月至2019年1月于上海交通大学医学院附属瑞金医院卢湾分院接受胃癌根治术30例病人肿瘤组织及癌旁相应正常组织作为研究对象,采用实时定量PCT(real-time PCR,RT-PCR)检测lncRNA-BBOX1-2和FGFR1表达;si-linc-BBOX1-2转染SGC-7901细胞后,通过蛋白质印迹法/细胞存活率分析(MTT)、细胞迁移和侵袭(Transwell)实验、细胞划痕、平板克隆一系列生物学功能实验,检测肿瘤细胞生物学功能及FGFR1表达的变化。结果胃癌组织中的lncRNA-BBOX1-2(3.68±0.58比1.15±0.11)和FGFR1(4.26±0.71比1.19±0.18)表达显著高于癌旁正常组织(P<0.05);si-linc-BBOX1-2转染SGC-7901细胞后,FGFR1表达下调,细胞活力、迁移、侵袭和生存能力明显下降。结论LincRNA-BBOX1-2可通过调控FGFR1的表达介导胃癌细胞的增殖、凋亡、迁移和侵袭,可能为胃癌的治疗提供了新的靶点和潜在的生物学标志物。 展开更多
关键词 胃肿瘤 长链非编码RNA BBOX1-2 成纤维细胞生长因子受体1 调控 增殖 凋亡
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血清sIL-2R联合TNF-α、IgG、IgA对多发性骨髓瘤患者复发的预测价值
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作者 林萍 张雅兰 +1 位作者 谢若腾 张学亚 《中国实验血液学杂志》 北大核心 2025年第1期150-156,共7页
目的:探讨血清可溶性白细胞介素-2受体(soluble interleukin-2 receptor,sIL-2R)、肿瘤坏死因子-α(TNF-α)、IgG、IgA对多发性骨髓瘤(multiple myeloma,MM)复发的预测价值。方法:选取2017年1月-2019年3月在本院初诊且治疗的MM患者108例... 目的:探讨血清可溶性白细胞介素-2受体(soluble interleukin-2 receptor,sIL-2R)、肿瘤坏死因子-α(TNF-α)、IgG、IgA对多发性骨髓瘤(multiple myeloma,MM)复发的预测价值。方法:选取2017年1月-2019年3月在本院初诊且治疗的MM患者108例,最终确定符合诊断标准且有完整随访资料的72例患者作为研究对象,以MM复发为研究终点事件,随访至终点事件的发生或本研究随访截止日期。根据是否复发,将MM分为复发组(RG)和非复发组(NRG)。在初诊时和随访后(终点事件的发生或研究终止时)分别采集患者静脉血,酶联免疫吸附测定法(ELISA)检测患者血清中sIL-2R和TNF-α水平;自动免疫分析仪检测患者血清中IgG、IgA水平;比较两组之间各因子表达水平的差异,并分析初诊时和随访后sIL-2R与TNF-α、IgG、IgA之间的相关性。同时在治疗完全缓解时采集患者静脉血,测定血清中sIL-2R水平,比较初诊时、完全缓解时和复发时sIL-2R表达水平的差异。采用受试者工作特征(ROC)曲线判断血清sIL-2R、TNF-α、IgG、IgA的最佳截断值,并根据曲线下面积(AUC)分析sIL-2R、TNF-α、IgG、IgA在MM复发中的预测价值。结果:MM患者初诊时和复发时血清sIL-2R水平均明显高于完全缓解时(P<0.05)。复发组初诊时的血红蛋白(Hb)含量低于未复发组,β2-微球蛋白(β2-MG)含量高于未复发组(P<0.001),两组间的其他临床参数无显著差异(P>0.05)。复发组初诊时和随访后的sIL-2R、TNF-α、IgG、IgA水平均明显高于未复发组(P<0.05),sIL-2R与TNF-α、IgG和IgA在初诊时和随访后均存在显著正相关(P<0.001)。ROC曲线分析结果显示,初诊时sIL-2R、TNF-α、IgG和IgA预测MM的AUC分别为0.919、0.850、0.766和0.795,随访后预测MM的AUC分别为0.890、0.815、0.760和0.794(P<0.001)。结论:血清sIL-2R对MM复发的预测价值最高,可在特定的时间检测TNF-α、IgG和IgA水平来推断sIL-2R水平的变化,从而评估患者的预后。 展开更多
关键词 可溶性白细胞介素-2受体 肿瘤坏死因子-α IGG IGA 多发性骨髓瘤 复发
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基于CT影像组学评估胃腺癌人表皮生长因子受体-2表达状态的价值
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作者 王素雅 詹鹏超 +4 位作者 邢静静 梁盼 岳松伟 张永高 高剑波 《放射学实践》 北大核心 2025年第1期9-15,共7页
目的:基于CT影像组学及临床特征建立可无创性评估胃腺癌人表皮生长因子受体2(HER-2)表达状态的预测模型,并验证其效能。方法:回顾性分析本院263例经病理确诊为胃腺癌患者的临床资料,其中HER-2阳性患者49例,阴性214例。将所有患者以7:3... 目的:基于CT影像组学及临床特征建立可无创性评估胃腺癌人表皮生长因子受体2(HER-2)表达状态的预测模型,并验证其效能。方法:回顾性分析本院263例经病理确诊为胃腺癌患者的临床资料,其中HER-2阳性患者49例,阴性214例。将所有患者以7:3的比例随机分为训练集(n=185)和验证集(n=78)。基于3D Slicer软件和门脉期CT图像手动勾画病灶感兴趣区(ROI),并提取影像组学特征。在训练集中,比较HER-2阳性与阴性组患者的临床特征差异,采用多因素Logistic回归确定临床独立预测因子,建立临床模型。基于最小绝对收缩和选择算子(LASSO)回归算法构建影像组学模型,计算影像组学分数(Radscore)。结合临床独立预测因子和Radscore构建联合模型。根据ROC曲线的曲线下面积(AUC)评估模型的预测效能,绘制校准曲线评价模型预测概率与真实概率之间的一致性,采用决策曲线(DCA)分析模型的临床价值。结果:肿瘤厚径(OR=1.04,P=0.033)、cT分期(OR=2.39,P=0.038)、cN分期(OR=2.15,P=0.046)为HER-2阳性表达的临床独立预测因子。在训练集中,临床模型、影像组学模型和联合模型预测胃癌HER-2阳性表达的的AUC分别为0.711(0.626~0.795)、0.852(0.787~0.917)和0.872(0.808~0.936);在验证集中,临床模型、影像组学模型和联合模型预测胃癌HER-2阳性表达的的AUC分别为0.698(0.534~0.861)、0.818(0.698~0.938)和0.853 (0.747~0.959)。校准曲线显示联合模型预测概率与真实概率之间的一致性良好,DCA结果显示联合模型可为胃腺癌患者提供临床净获益。结论:基于CT影像组学和临床特征构建的联合模型可用于治疗前无创性评估胃腺癌的HER-2表达状态。 展开更多
关键词 胃肿瘤 人表皮生长因子受体-2 表达状态 体层摄影术 X线计算机 影像组学
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COX-2在骨骼肌纤维化中的机制探究
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作者 李佳 丁见 +3 位作者 陈欢 缪化春 龚鑫 丁艳霞 《包头医学院学报》 CAS 2024年第11期15-18,35,共5页
目的:探究环氧化酶-2(cyclooxygenase-2,COX-2)在骨骼肌纤维化机制中的作用及其与Wnt/β-catenin信号通路的关系。方法:72只20周雄性C57小鼠,随机分为正常组、模型组、干预组。采用定点击打法造骨骼肌损伤模型。正常组不进行造模,模型... 目的:探究环氧化酶-2(cyclooxygenase-2,COX-2)在骨骼肌纤维化机制中的作用及其与Wnt/β-catenin信号通路的关系。方法:72只20周雄性C57小鼠,随机分为正常组、模型组、干预组。采用定点击打法造骨骼肌损伤模型。正常组不进行造模,模型组和干预组进行造模处理。造模成功后,正常组、模型组给予每日1 mL生理盐水灌胃处理,干预组给予每日COX-2特异性抑制剂塞来昔布灌胃处理,剂量为100 mg/kg溶于1 mL生理盐水中。每组根据取材时间又分为3 d、7 d、14 d、21 d四个亚组(n=6)。采用免疫组织化学染色方法检测各组骨骼肌组织切片中COX-2和β-catenin的表达情况。结果:正常组小鼠骨骼肌组织中COX-2和β-catenin呈少量表达。与正常组相比,模型组COX-2和β-catenin表达均明显增加(P<0.01)。与模型组相比,干预组COX-2和β-catenin表达明显减少(P<0.01)。结论:COX-2在骨骼肌纤维化中可能通过干预β-catenin的表达来产生影响。 展开更多
关键词 骨骼肌 纤维化 cox-2 Β-CATENIN
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助孕宁Ⅱ号方调控LPAR3/COX-2/PGE2通路改善PCOS先兆流产大鼠的作用机制研究
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作者 曹雯雯 韩其茂 +3 位作者 谷玥儒 李强 冯晓玲 陈璐 《时珍国医国药》 CAS CSCD 北大核心 2024年第3期541-544,共4页
目的基于LPAR3/COX-2/PGE2通路探讨助孕宁Ⅱ号方对PCOS先兆流产大鼠的影响及作用机制。方法36只SD雌性大鼠随机分为助孕宁Ⅱ号方高、中、低剂量组、西药(地屈孕酮)组、模型组、空白组,每组6只,除空白组外均采用胰岛素和HCG联合注射法构... 目的基于LPAR3/COX-2/PGE2通路探讨助孕宁Ⅱ号方对PCOS先兆流产大鼠的影响及作用机制。方法36只SD雌性大鼠随机分为助孕宁Ⅱ号方高、中、低剂量组、西药(地屈孕酮)组、模型组、空白组,每组6只,除空白组外均采用胰岛素和HCG联合注射法构建PCOS模型大鼠,予来曲唑促排卵构建PCOS先兆流产模型大鼠。各组大鼠于妊娠第1天开始连续灌服不同药物干预,于妊娠第7天处死。收集大鼠血清,采用ELISA法检测药物干预前后各组大鼠血清P、E2、β-hCG、COX-2、PGE2及VEGF水平变化;RT-PCR、Western Blot法测定药物干预前后各组PCOS先兆流产大鼠蜕膜组织中LPAR3、COX-2、PGE2、VEGF mRNA含量及蛋白表达水平。结果与空白组相比,模型组血清E2、P、β-hCG、COX2、PGE2、VEGF水平均降低(P<0.01),蜕膜组织LPAR3、COX-2、PGE2及VEGF的mRNA及蛋白质水平均降低(P<0.05);与模型组比较,助孕宁Ⅱ号方可提高大鼠血清E2、P、β-hCG、COX2、PGE2、VEGF,其中高、中剂量均可升高E2、PGE2水平(P<0.01),高剂量可升高P、VEGF水平(P<0.01),中剂量可升高β-hCG水平(P<0.05),高、中、低剂量均可升高COX-2水平(P<0.01)。助孕宁Ⅱ号方可增加大鼠蜕膜组中LPAR3、COX-2、PGE2及VEGF mRNA含量及蛋白表达水平,其中,增加mRNA含量上,高剂量疗效最佳(P<0.05);在增强蛋白表达水平上,高、中剂量均可收到良好疗效(P<0.05)。结论助孕宁Ⅱ号方可以改善PCOS先兆流产性激素水平,改善妊娠结局,其机制可能与调节LPAR3/COX-2/PGE2通路有关。 展开更多
关键词 多囊卵巢综合征 先兆流产 助孕宁Ⅱ号方 LPAR3/cox-2/PGE2通路
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基于COX-2/PGE2信号通路探讨温肾消癥汤减轻子宫内膜异位症小鼠疼痛的作用机制
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作者 汪逸纯 万贵平 张真真 《浙江中医药大学学报》 CAS 2024年第10期1199-1208,1223,共11页
[目的]基于环氧合酶-2/前列腺素E2(cyclooxyfenase-2/prostaglandin E2,COX-2/PGE2)信号通路,探讨温肾消癥汤对子宫内膜异位症(endometriosis,EMS)模型小鼠疼痛的影响及其作用机制。[方法]采用腹腔注射法建立EMS小鼠模型40只作为造模组... [目的]基于环氧合酶-2/前列腺素E2(cyclooxyfenase-2/prostaglandin E2,COX-2/PGE2)信号通路,探讨温肾消癥汤对子宫内膜异位症(endometriosis,EMS)模型小鼠疼痛的影响及其作用机制。[方法]采用腹腔注射法建立EMS小鼠模型40只作为造模组,并随机将造模组分为EMS模型组(0.2 mL无菌蒸馏水)、温肾消癥汤组(0.2 mL温肾消癥汤浓缩液)、阳性对照组(0.2 mL阿司匹林混悬液),其他10只小鼠设为假手术组。造模21 d中,以Von Frey纤维丝实验与热板实验检测造模组与假手术组小鼠机械疼痛与热敏疼痛阈值。给药的21 d中,以Von Frey纤维丝实验与热板实验检测EMS模型组、温肾消癥汤组、阳性对照组小鼠机械疼痛与热敏疼痛阈值。给药21 d后,每天阴道涂片确定小鼠动情周期。在同一动情周期处死小鼠,并留取血清,腹腔冲洗液(peritoneal fluid,PF),内膜组织(在位、异位),丘脑,脊髓,背根神经节(dorsal root ganglion,DRG)。以酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)测定各样本中COX-2、PGE2、瞬时电位受体V1(transient receptor potential vanilloid 1,TRPV1)、钠电压门控通道α亚基11(sodium channel protein type 11 subunit alpha,SCN11A)含量。[结果]与假手术组比较,造模后小鼠足部与腹部痛阈均降低(P<0.05)。与EMS模型组比较,温肾消癥汤组小鼠给药后足部痛阈、腹部痛阈均提高(P<0.05)。与EMS模型组比较,温肾消癥汤组小鼠血清,在位内膜,PF,神经系统(丘脑、脊髓、DRG)中COX-2、PGE2,中枢神经系统(丘脑、脊髓)中TRPV1和外周神经系统(DRG)中SCN11A含量均降低(P<0.05)。与阳性对照组比较,温肾消癥汤组小鼠给药后血清、异位病灶、脊髓中PGE2含量均降低(P<0.05)。[结论]温肾消癥汤能够缓解子宫内膜异位症模型小鼠疼痛,其机制可能与抑制COX-2/PGE2信号通路的过度表达有关。 展开更多
关键词 子宫内膜异位症 疼痛 cox-2 PGE2 中枢敏化 外周敏化
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獐牙菜苦苷、灵仙新苷组分配伍对RA模型大鼠血清学指标及踝关节COX-2的影响
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作者 郝倩莹 高慧琴 +2 位作者 吴国泰 李飒 王丽明 《时珍国医国药》 CAS CSCD 北大核心 2024年第5期1034-1040,共7页
目的探讨獐牙菜苦苷、灵仙新苷组分配伍对类风湿关节炎(Rheumatoid arthritis,RA)模型大鼠血清学指标及踝关节COX-2的影响。方法选取SPF级SD大鼠5~6周龄36只,雌雄各半。除空白组外,均采用II型胶原诱导法复制(Collagen induced arthritis... 目的探讨獐牙菜苦苷、灵仙新苷组分配伍对类风湿关节炎(Rheumatoid arthritis,RA)模型大鼠血清学指标及踝关节COX-2的影响。方法选取SPF级SD大鼠5~6周龄36只,雌雄各半。除空白组外,均采用II型胶原诱导法复制(Collagen induced arthritis,CIA)大鼠模型。将造模成功的30只大鼠按随机数字表法分为模型组、阳性药(正清风痛宁)组、獐牙菜苦苷组、灵仙新苷组、獐牙菜苦苷配伍灵仙新苷组(以下简称“獐-灵配伍组”),每组6只。给药组分别给予相应药液灌胃,模型组和空白组给予等量生理盐水灌胃,连续灌胃10 d。实验中对各组大鼠进行一般状态观察记录、关节炎评分(AI),苏木素-伊红(HE)染色法观察大鼠踝关节组织病理变化;酶联免疫吸附测定法(ELISA)检测大鼠血清中肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、类风湿因子(RF)、C反应蛋白(CRP)、抗环瓜氨酸肽抗体(anti-CCP Ab)及前列腺素E2(PGE2)含量;免疫组织化学法(Immunohistochemistry)及蛋白免疫印迹法(Western blot)检测大鼠踝关节环氧化酶-2(COX-2)蛋白表达;实时荧光定量聚合酶链式反应法(Real-time PCR)检测大鼠踝关节COX-2基因表达。结果与空白组比较,模型组大鼠一般状态较差,大鼠左后足趾AI评分及血清中TNF-α、IL-1β、RF、CRP、anti-CCP Ab、PGE2含量显著高于其他组(P<0.05或P<0.01);踝关节组织结构严重破坏,COX-2蛋白及基因表达显著上调(P<0.01)。与模型组比较,各给药组大鼠一般状态呈不同程度好转;AI评分明显降低(P<0.01),血清中TNF-α、IL-1β、RF、CRP、anti-CCP、PGE2含量明显降低(P<0.05或P<0.01),其中獐-灵配伍组抑制TNF-α、RF、CRP、anti-CCP、PGE2作用最为突出;獐牙菜苦苷在抑制IL-1β作用最突出。踝关节组织病理状态均有不同程度改善;IHC及WB检测结果显示獐-灵配伍组降低踝关节COX-2蛋白表达水平最为显著(P<0.01);PCR检测结果显示獐牙菜苦苷组降低踝关节COX-2基因表达最为显著(P<0.01)。结论獐牙菜苦苷、灵仙新苷及其配伍对RA模型大鼠能起到良好的治疗作用,其中獐-灵配伍组的治疗效果明显优于各单体给药组;獐牙菜苦苷与灵仙新苷具有明显的协同增效作用,其作用机制可能是通过降低炎性细胞因子的分泌,抑制COX-2蛋白活性而发挥作用。 展开更多
关键词 獐牙菜苦苷 灵仙新苷 组分配伍 类风湿关节炎 cox-2
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沙利度胺对百草枯中毒大鼠肺纤维化及COX-2的影响
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作者 刘诗文 邱东东 +6 位作者 李菁 袁思思 宋元 杨继斌 林时荣 周从阳 黄子炎 《哈尔滨医药》 2024年第5期51-54,共4页
目的探究沙利度胺对于百草枯中毒大鼠肺纤维化以及COX-2的影响。方法选取60只雄性SD大鼠按照随机数字表法分为百草枯中毒模型组(PQ组)10只、沙利度胺干预组30只、正常对照组(NS组)10只、沙利度胺对照组10只。百草枯组腹腔注射百草枯溶液... 目的探究沙利度胺对于百草枯中毒大鼠肺纤维化以及COX-2的影响。方法选取60只雄性SD大鼠按照随机数字表法分为百草枯中毒模型组(PQ组)10只、沙利度胺干预组30只、正常对照组(NS组)10只、沙利度胺对照组10只。百草枯组腹腔注射百草枯溶液22mg/kg;沙利度胺对照组腹腔注射沙利度胺150mg/kg;沙利度胺干预组按照随机数字表法分为三组,每组10只,在注射百草枯溶液后1h,分别给予注射50、100、150mg/kg沙利度胺;正常对照组注射等体积注射生理盐水。染毒后7、14、21d分别处死实验大鼠,无菌操作取肺,光镜下观察肺组织病理变化;计算肺干湿比;大鼠肺组织氧化损伤指标MDA、SOD、GSH的比较;采用双抗体夹心ELISA法测定肺组织中肿瘤坏死因子(TNF-a)、白细胞介素(IL)-1β、IL-6水平;RT-PCR检测NF-kB p65mRNA表达量;免疫组化法检测肺组织中COX-2蛋白的表达。结果与正常对照组相比,百草枯中毒组肺干湿比质量显著高,差异具有统计学意义(P<0.05);沙利度胺干预组150mg/kg与百草枯中毒21d都达到顶峰,差异具有统计学意义(P<0.05);与正常对照组相比,百草枯中毒组大鼠组织中的MDA的含量明显升高,SOD和GSH的含量明显降低(P<0.05);与百草枯中毒组对比沙利度胺干预组100、150mg/kg组大鼠肺组织中的MDA明显降低,SOD和GSH的含量明显升高;与正常对照组相比,百草枯中毒组大鼠中的TNF-a、IL-1β、IL-6的含量以及NF-kBP65mRNA表达量明显升高(P<0.05);与百草枯中毒组对比沙利度胺干预组100、150mg/kg组TNF-a、IL-1β、IL-6明显降低(P<0.05);沙利度胺干预组150mg/kg较百草枯中度组差异具有统计学意义(P<0.05);在第21天PQ组和沙利度胺干预组150mg/kgCOX-2分别达到最高值:PQ组(0.701±0.083),沙利度胺干预组150mg/kg组(0.416±0.096。结论沙利度胺能减轻百草枯诱导的急性肺损伤和肺水肿,COX-2的表达异常可能是其病理生理变化或发病机制之一。 展开更多
关键词 沙利度胺 百草枯 肺纤维化 cox-2
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PRaG 3.0 therapy for human epidermal growth factor receptor 2-positive metastatic pancreatic ductal adenocarcinoma:A case report 被引量:2
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作者 Yue-Hong Kong Mei-Ling Xu +10 位作者 Jun-Jun Zhang Guang-Qiang Chen Zhi-Hui Hong Hong Zhang Xiao-Xiao Dai Yi-Fu Ma Xiang-Rong Zhao Chen-Yang Zhang Rong-Zheng Chen Peng-Fei Xing Li-Yuan Zhang 《World Journal of Gastroenterology》 SCIE CAS 2024年第9期1237-1249,共13页
BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemis... BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.CASE SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month.She had not developed any grade 2 or above treatment-related adverse events at any point.Percentage of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.CONCLUSION PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials. 展开更多
关键词 Pancreatic ductal adenocarcinoma PRaG 3.0 therapy Human epidermal growth factor receptor 2 Novel combination therapy Case report
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Leukocyte immunoglobulin-like receptor B2:A promising biomarker for colorectal cancer 被引量:1
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作者 Wen-Zhuo Zhao Hong-Gang Wang Xiao-Zhong Yang 《World Journal of Gastroenterology》 SCIE CAS 2024年第4期421-423,共3页
According to the latest global cancer statistics,colorectal cancer(CRC)has emerged as the third most prevalent malignant tumor across the globe.In recent decades,the medical field has implemented several levels of CRC... According to the latest global cancer statistics,colorectal cancer(CRC)has emerged as the third most prevalent malignant tumor across the globe.In recent decades,the medical field has implemented several levels of CRC screening tests,encompassing fecal tests,endoscopic examinations,radiological examinations and blood tests.Previous studies have shown that leukocyte immunoglobulin-like receptor B2(LILRB2)is involved in inhibiting immune cell function,immune evasion,and promoting tumor progression in acute myeloid leukemia and nonsmall cell lung cancer.However,its interaction with CRC has not been reported yet.Recently,a study published in the World Journal of Gastroenterology revealed that LILRB2 and its ligand,angiopoietin-like protein 2,are markedly overexpressed in CRC.This overexpression is closely linked to tumor progression and is indicative of a poor prognosis.The study highlights the potential of utilizing the concentration of LILRB2 in serum as a promising biomarker for tumors.However,there is still room for discussion regarding the data processing and analysis in this research. 展开更多
关键词 Colorectal cancer Leukocyte immunoglobulin-like receptor B2 Angiopoietinlike protein 2 Therapeutic target Noninvasive screening biomarker
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原发性喉癌血清COX-2 PTTG1 TLR4水平与临床病理特征及预后生存状况的关系探讨
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作者 吴建 杨令 王东 《河北医学》 CAS 2024年第9期1525-1530,共6页
目的:探究原发性喉癌血清环氧合酶-2(COX-2)、垂体瘤转化基因1(PTTG1)、Toll样受体4(TLR4)水平与临床病理特征及预后生存状况的关系。方法:选取2021年5月至2023年3月四川省达州市中心医院105例原发性喉癌患者、105例喉部良性病变患者分... 目的:探究原发性喉癌血清环氧合酶-2(COX-2)、垂体瘤转化基因1(PTTG1)、Toll样受体4(TLR4)水平与临床病理特征及预后生存状况的关系。方法:选取2021年5月至2023年3月四川省达州市中心医院105例原发性喉癌患者、105例喉部良性病变患者分别作为观察组和对照组。比较两组血清COX-2、PTTG1、TLR4水平,多元线性回归分析血清COX-2、PTTG1、TLR4水平与临床病理特征的关系,随访3年,比较不同血清COX-2、PTTG1、TLR4水平患者预后生存率。结果:观察组COX-2、PTTG1、TLR4水平分别为(38.89±12.14)ng/L、(140.17±30.25)pg/mL、(13.94±3.25)ng/mL均高于对照组(17.63±5.09)ng/L、(98.49±15.63)pg/mL、(8.72±2.13)ng/mL(t=16.549、12.543、13.765,P均<0.05);多元线性回归分析显示,临床分期(偏回归系数:0.714、0.722、0.719)、肿瘤分化程度(偏回归系数:0.756、0.749、0.798)及淋巴结转移(偏回归系数:0.802、0.798、0.713)均为原发性喉癌患者血清COX-2、PTTG1、TLR4水平的影响因素(P<0.05);COX-2高水平亚组3年总生存率、总生存率分别为80.77%、71.15%,明显高于低水平亚组95.83%、87.50%(P<0.05);PTTG1高水平亚组3年总生存率、总生存率分别为80.39%、68.63%,明显高于低水平亚组95.92%、89.80%(P<0.05);TLR4高水平亚组3年总生存率、总生存率分别为78.85%、71.15%,明显高于低水平亚组97.92%、87.50%(P<0.05)。结论:原发性喉癌患者血清COX-2、PTTG1、TLR4水平均较高,且其高水平状态与临床分期、肿瘤分化程度及淋巴结转移有关,检测COX-2、PTTG1、TLR4水平可在一定程度上反映患者预后生存情况。 展开更多
关键词 原发性喉癌 病理特征 预后生存 cox-2 PTTG1 TLR4
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肉桂提取物调控COX-2的表达改善大鼠良性前列腺增生
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作者 孔维桂 刘丽丽 +3 位作者 王瑶 宋蕴洋 江淑琴 戴荣华 《沈阳药科大学学报》 CAS CSCD 2024年第4期409-416,共8页
目的研究肉桂乙醇提取物(Cinnamomum cassia Prsel ethanol extract,CE)对良性前列腺增生(benign prostatic hyperplasa,BPH)的治疗作用及其可能的作用机制。方法分子对接初步推测CE中3种化合物对环氧合酶-2(cyclooxygenase-2,COX-2)和5... 目的研究肉桂乙醇提取物(Cinnamomum cassia Prsel ethanol extract,CE)对良性前列腺增生(benign prostatic hyperplasa,BPH)的治疗作用及其可能的作用机制。方法分子对接初步推测CE中3种化合物对环氧合酶-2(cyclooxygenase-2,COX-2)和5-脂氧合酶(5-lipoxygenase,5-LOX)的结合能力。考察前列腺湿重(prostate weight,PW)、前列腺指数(prostate index,PI),并采用苏木精-伊红染色(hematoxylin-esion staining,HE)观察大鼠前列腺组织的形态变化;Western-blot和q-PCR检测大鼠前列腺组织中COX-2和5-LOX的蛋白、mRNA表达水平。结果分子对接结果表明,CE中3种主要活性单体化合物与COX-2及5-LOX蛋白模型均有较好的结合能;Western-blot和q-PCR结果显示,CE能同时降低COX-2及5-LOX在蛋白和mRNA水平上的表达,对COX-2的下调具有显著性;PW、PI及组织病理学切片均表明肉桂能改善BPH。结论CE能够有效改善BPH,其机制可能与下调花生四烯酸代谢网络中的COX-2的表达相关。 展开更多
关键词 良性前列腺增生 分子对接 5-LOX cox-2 肉桂乙醇提取物
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选择性COX-2抑制剂联合抗血管药物对肺癌影响的研究进展
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作者 武婷婷 张卿 《内蒙古医学杂志》 2024年第4期461-463,467,共4页
肺癌是全球男性常见癌症,大部分肺癌患者在确诊时已属晚期。对于肺癌晚期患者来说,放疗、化疗的不良反应较大,患者无法耐受;靶向药物普遍存在耐药现象;免疫治疗受程序性死亡配体-1(programmed cell death protein 1,PD-L1)的表达限制;... 肺癌是全球男性常见癌症,大部分肺癌患者在确诊时已属晚期。对于肺癌晚期患者来说,放疗、化疗的不良反应较大,患者无法耐受;靶向药物普遍存在耐药现象;免疫治疗受程序性死亡配体-1(programmed cell death protein 1,PD-L1)的表达限制;抗血管治疗的出现为晚期肺癌患者提供了更多的选择。目前,多种药物联合治疗肺癌的手段日渐成熟,抗血管药物联合化疗药物或靶向药物都取得了显著的疗效。在肺癌肿瘤生长过程中,环氧化酶-2(cyclooxygenase-2,COX-2)和血管内皮生长因子(vascular endothelial growth factor,VEGF)相互促进使肿瘤血管新生,所以,选择性COX-2抑制剂联合抗血管药物是否具有协同抗肿瘤作用,其抗肿瘤机制如何,本文将针对以上问题展开论述。 展开更多
关键词 非小细胞肺癌 cox-2抑制剂 抗血管药物
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