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Increased Incidence of Severe Adverse Events in Non-Small Cell Lung Cancer Patients with Previous Tuberculosis Episode Treated with PD-1 Inhibitors
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作者 Hui Zhang Jinfeng Yuan +8 位作者 Yuanyuan Xu Mengjie yang Jialin Lyu xinjie yang Shuyan Sheng Zhe Qian Qunhui Wang Yu Pang Ying Hu 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 2024年第7期785-789,共5页
Lung cancer is the top cause of cancer deaths globally.Advances in immune checkpoint inhibitors(ICIs)have transformed cancer treatment,but their use in lung cancer has led to more side effects.This study examined if p... Lung cancer is the top cause of cancer deaths globally.Advances in immune checkpoint inhibitors(ICIs)have transformed cancer treatment,but their use in lung cancer has led to more side effects.This study examined if past pulmonary tuberculosis(TB)affects ICIs’effectiveness and safety in lung cancer treatment.We reviewed lung cancer patients treated with ICIs at Beijing Chest Hospital from January 2019 to August 2022. 展开更多
关键词 LUNG LUNG Cancer
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微滴数字PCR和Super-ARMS检测晚期肺腺癌患者血浆循环肿瘤DNA表皮生长因子受体基因突变的临床价值研究 被引量:15
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作者 曹喆 王静 +11 位作者 秦娜 李琨 吕嘉林 王敬慧 杨新杰 李曦 张卉 张权 龙洪清 舒诚荣 马丽 张树才 《中国肺癌杂志》 CAS CSCD 北大核心 2020年第2期84-90,共7页
背景与目的晚期肺腺癌患者在选择靶向药物时需以肿瘤表皮生长因子受体(epidermal growth factor receptor, EGFR)基因突变类型作为依据,然而晚期肺腺癌肿瘤组织取材较难,有专家共识指出外周血可替代肿瘤组织作为检测标本。本文旨在探讨... 背景与目的晚期肺腺癌患者在选择靶向药物时需以肿瘤表皮生长因子受体(epidermal growth factor receptor, EGFR)基因突变类型作为依据,然而晚期肺腺癌肿瘤组织取材较难,有专家共识指出外周血可替代肿瘤组织作为检测标本。本文旨在探讨微滴数字聚合酶链反应法(droplet digital polymerase chain reaction, ddPCR)和超级扩增阻滞突变系统(super-amplification refractory mutation system, super-ARMS)这两种方法检测晚期肺腺癌患者外周血中血浆循环肿瘤脱氧核糖核酸(circulating tumor DNA, ctDNA)中EGFR基因突变的临床价值。方法收集2016年2月-2019年2月首都医科大学附属北京胸科医院确诊的初治晚期肺腺癌共119例纳入研究,比较ddPCR和Super-ARMS技术检测血浆ctDNA EGFR基因突变的敏感度、特异度。部分EGFR基因经典突变阳性患者接受一线EGFR酪氨酸激酶抑制剂(EGFR tyrosine kinase inhibitors, EGFR-TKI)口服治疗,将患者按检测结果分亚组,组1为ddPCR及Super-ARMS检测EGFR基因突变结果均为阳性,21例。组2为ddPCR及Super-ARMS检测EGFR基因突变结果均为阴性,16例。组3为ddPCR检测结果为阳性而Super-ARMS检测结果为阴性,5例。组4为ddPCR检测结果为阴性而Super-ARMS检测结果阳性,因组4患者个数为0,不纳入统计。以客观缓解率(objective response rate, ORR)及疾病控制率(disease control rate, DCR)评估近期疗效,并用生存分析比较组间无进展生存时间(progression-free survival, PFS)以评估远期疗效。结果 119例晚期肺腺癌组织样本中,共检测到58例(48.7%)EGFR基因突变。ddPCR技术检测与肿瘤组织EGFR基因突变结果的符合率为82.4%(Kappa=0.647, P<0.001),灵敏度为74.1%,特异度为90.2%。而Super-ARMS检测与组织检测的符合度为71.4%,灵敏度仅为58.6%,特异度为83.6%。组3的ORR与DCR值低于组1、2,但组间ORR相比均无统计学意义(P>0.05)。生存分析显示,三组患者PFS比较,差异无统计学意义(χ~2=2.221, P=0.329)。结论 ddPCR作为一种高敏感度及特异度的液体基因检测方法,可以作为检测晚期肺腺癌患者血浆ctDNA EGFR基因突变的一种较为可靠的方法。血浆基因检测结果同样可作为EGFR-TKIs药物对患者的疗效预测的依据。 展开更多
关键词 肺肿瘤 微滴数字聚合酶链反应 表皮生长因子受体 基因突变 循环肿瘤脱氧核糖核酸 突变扩增系统 Super-突变扩增系统
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405例肺癌合并肺结核患者临床特征及驱动基因检测分析 被引量:10
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作者 胡瑛 杨新杰 +3 位作者 聂理会 赵丹 安军 李宝兰 《中国肺癌杂志》 CAS CSCD 北大核心 2020年第5期337-342,共6页
背景与目的随着肺癌研究进展,靶向治疗、免疫检查点抑制剂等新的治疗方法已经开始应用于肺癌患者,因此需要进一步了解合并肺结核的肺癌患者的临床及实验室特点,从而为此类患者的临床治疗提供新的思路。本研究目的是分析肺癌合并肺结核... 背景与目的随着肺癌研究进展,靶向治疗、免疫检查点抑制剂等新的治疗方法已经开始应用于肺癌患者,因此需要进一步了解合并肺结核的肺癌患者的临床及实验室特点,从而为此类患者的临床治疗提供新的思路。本研究目的是分析肺癌合并肺结核患者的临床特征、驱动基因检测结果及其之间关系。方法回顾性分析我院2014年1月-2019年12月收治的405例肺癌合并肺结核患者,应用统计学方法分析其临床特征与驱动基因状态之间的关系。结果405例肺癌合并肺结核患者中男性占77.3%,有吸烟史患者占85.3%,病理类型以肺腺癌为主,当胸部影像学有空洞改变时以鳞癌为主要类型。214例患者进行驱动基因检测,表皮生长因子受体(epidermal growth factor receptor,EGFR)基因突变率为35.9%,其中41.8%为外显子19缺失突变,50.9%为外显子21 L858R突变。当胸部影像有空洞改变时,EGFR突变率显著降低(16.1%)。间变性淋巴瘤激酶(anaplastic lymphoma kinase,ALK)融合基因检测阳性率为2.5%,原癌基因1酪氨酸激酶(c-ros oncogene 1 receptorkinase,ROS1)突变率为1.9%,肉瘤病毒致癌基因同源物B1(V-raf murine sarcoma viral oncogene homolog B1,BRAF)基因突变率为1.1%,克尔斯滕大鼠肉瘤病毒致癌基因同源物(Kirsten Rat Sarcoma Viral Oncogene Homolog,KRAS)基因突变率为10.1%。女性肺癌合并肺结核患者基因突变率为50.0%,男性为27.9%。结论肺癌合并肺结核患者以有吸烟史的男性患者为主,病理类型以腺癌为主。基因突变阳性率与单纯肺癌无明显差异,但是当胸部影像有空洞表现时,基因突变率显著降低。 展开更多
关键词 肺肿瘤 肺结核 驱动基因
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驱动基因阳性且PD-L1高表达的非小细胞肺癌患者病理特征及靶向治疗疗效评估的真实世界研究 被引量:6
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作者 张卉 杨新杰 +11 位作者 李琨 王敬慧 吕嘉林 李曦 张新勇 秦娜 张权 吴羽华 马丽 盖飞 胡瑛 张树才 《中国肺癌杂志》 CAS CSCD 北大核心 2021年第2期78-87,共10页
背景与目的驱动基因突变阳性患者行靶向治疗,驱动基因阴性但程序性死亡配体1(programmed death-ligand 1,PD-L1)高表达患者行免疫抑制剂治疗,是晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者一线治疗的首选,但对于驱动基因... 背景与目的驱动基因突变阳性患者行靶向治疗,驱动基因阴性但程序性死亡配体1(programmed death-ligand 1,PD-L1)高表达患者行免疫抑制剂治疗,是晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者一线治疗的首选,但对于驱动基因阳性且PD-L1高表达患者的治疗选择仍值得探究。方法以315例NSCLC患者为研究对象,分析驱动基因阳性且PD-L1高表达患者的临床病理特征及靶向治疗疗效。结果本研究纳入的315例NSCLC患者中,驱动基因突变总阳性率为62.2%,PD-L1高表达率(≥50.0%)为11.2%,驱动基因阳性且PD-L1高表达的患者比例为10.7%。其中表皮生长因子受体(epidermal growth factor receptor,EGFR)突变、KRAS突变、ALK融合、BRAF突变和MET 14外显子跳跃突变患者中均有PD-L1高表达,比例分别为7.8%(11/141)、18.2%(4/22)、23.1%(3/13)、50.0%(2/4)和100.0%(1/1)。EGFR突变且PD-L1高表达患者主要为IV期肺腺癌患者,KRAS突变且PD-L1高表达患者主要为有吸烟史的患者。其中详细跟踪了两例分别为ALK融合阳性且PD-L1高表达(90.0%)和EGFR L858R突变且PD-L1高表达(70.0%)患者的靶向治疗全过程,两例患者总生存期分别仅为5个月和2个月。结论NSCLC患者各驱动基因突变与PD-L1高表达共存的比例和临床病理特征有较大差异。发生敏感突变且PD-L1高表达的患者靶向治疗疗效和预后可能更差。 展开更多
关键词 肺肿瘤 驱动基因 程序性死亡配体1 靶向治疗
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Inhibition of growth and metastasis of triple-negative breast cancer targeted by Traditional Chinese Medicine Tubeimu in orthotopic mice models 被引量:10
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作者 Jingxiao Wang xinjie yang +8 位作者 Haibo Han Limin Wang Weiqian Bao Shanshan Wang Robert M.Hoffman Meng yang Hui Qi Chao An Kaiwen Hu 《Chinese Journal of Cancer Research》 SCIE CAS CSCD 2018年第1期112-121,共10页
Objective: Triple-negative breast cancer(TNBC) is highly invasive and metastatic, which is in urgent need of transformative therapeutics. Tubeimu(TBM), the rhizome of Bolbostemma paniculatum(Maxim.) Franquet, i... Objective: Triple-negative breast cancer(TNBC) is highly invasive and metastatic, which is in urgent need of transformative therapeutics. Tubeimu(TBM), the rhizome of Bolbostemma paniculatum(Maxim.) Franquet, is one of the Chinese medicinal herbs used for breast diseases since the ancient times. The present study evaluated the efficacy, especially the anti-metastatic effects of the dichloromethane extract of Tubeimu(ETBM) on TNBC orthotopic mouse models and cell lines.Methods: We applied real-time imaging on florescent orthotopic TNBC mice model and tested cell migration and invasion abilities with MDA-MB-231 cell line. Digital gene expression sequencing was performed and Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis applied to explore the pathways influenced by ETBM.Moreover, quantitative real-time polymerase chain reactions(q RT-PCR) and Western blot were delivered to confirm the gene expression changes.Results: ETBM exhibited noticeable control on tumor metastasis and growth of TNBC tumors with no obvious toxicity. In compliance with this, it also showed inhibition of cell migration and invasion in vitro. Its impact on the changed biological behavior in TNBC may be a result of decreased expression of integrin β1(ITGβ1), integrin β8(ITGβ8) and Rho GTPase activating protein 5(ARHGAP5), which disabled the focal adhesion pathway and caused change in cell morphology.Conclusions: This study reveals that ETBM has anti-metastatic effects on MDA-MB-231-GFP tumor and may lead to a new therapeutic agent for the integrative treatment of highly invasive TNBC. 展开更多
关键词 Tubeimu triple negative breast cancer(TNBC) orthotopic mouse models Traditional Chinese Medicine(TCM) integrins Rho GTPase activating protein 5
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The Current Analysis of Protection Path of Farmers' Rights and Causes
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作者 xinjie yang 《International Journal of Technology Management》 2014年第11期121-123,共3页
The problem of Chinese peasant in society is a very important issue in the process of China' s legal system; the farmer is very worthy subject of rights concern. The author believes that China has the right to protec... The problem of Chinese peasant in society is a very important issue in the process of China' s legal system; the farmer is very worthy subject of rights concern. The author believes that China has the right to protect their farmers in three main ways: private relief, public relief and gray channels, which play a major role in the private relief for farmers. For these channels, they are a unique reason; the rule of law should be the vision and balance for them to choose their own presence in China. 展开更多
关键词 Farmers' Rights PROTECTION RELIEF
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Divergent Protein Engineering of Transaminase for the Synthesis of Chiral Rivastigmine and Apremilast Precursors
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作者 Langyu Tang xinjie yang +3 位作者 Ningning Sun Guojiao Wu Yuzhou Wu Fangrui Zhong 《Chinese Journal of Chemistry》 SCIE CAS CSCD 2024年第19期2335-2340,共6页
Comprehensive Summary The implementation of divergent protein engineering on the natural transaminase Vf-ω-TA led to the development of two effective mutants(M2 and M8),enabling the enzymatic synthesis of chiral amin... Comprehensive Summary The implementation of divergent protein engineering on the natural transaminase Vf-ω-TA led to the development of two effective mutants(M2 and M8),enabling the enzymatic synthesis of chiral amine precursors of Rivastigmine and Apremilast,respectively.The evolution of the enzymes was guided by crystal structures and a focused mutagenesis strategy,allowing them to effectively address the challenging ketone substrates with significant steric hindrance.Under the optimized reaction parameters,transamination proceeded smoothly in good conversions and with perfect stereochemical control(>99%ee).These processes utilize inexpensiveα-methylbenzylamine as an amine donor and avoid the continuous acetone removal and costly LDH/GDH/NADH systems. 展开更多
关键词 Asymmetric catalysis Chiral amine Protein engineering Directed evolution BIOCATALYSIS TRANSAMINASE ENANTIOSELECTIVITY Syntheticmethods AMINATION Enzymes
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