资源类型

期刊论文 204

会议视频 40

会议信息 3

年份

2024 1

2023 20

2022 36

2021 69

2020 52

2019 14

2018 7

2017 1

2016 3

2015 2

2014 4

2013 5

2012 2

2011 2

2010 3

2009 4

2008 3

2007 6

2000 1

1999 1

展开 ︾

关键词

COVID-19 15

新冠病毒肺炎 11

钢结构 10

农业科学 7

国际工程 7

SARS-CoV-2 5

临床特征 3

临床试验 3

新型冠状病毒肺炎 3

2021全球十大工程成就 2

2022全球十大工程成就 2

中药 2

人工智能 2

保持社交距离 2

医学 2

口罩 2

大流行 2

安全性 2

嵌合抗原受体 2

展开 ︾

检索范围：

排序： 展示方式：

Tumor-derived exosomes induce initial activation by exosomal CD19 antigen but impair the function ofCD19-specific CAR T-cells via TGF-β signaling

《医学前沿（英文）》 doi: 10.1007/s11684-023-1010-1

摘要： Tumor-derived exosomes induce initial activation by exosomal CD19 antigen but impair the function of CD19-specific CAR T-cells via TGF-β signaling

关键词： exosomes induce activation     impair function CD19     exosomal CD19 antigen    

HTML PDF 收藏

Preclinical characterization and comparison between CD3/CD19 bispecific and novel CD3/CD19/CD20 trispecific

《医学前沿（英文）》 2022年 第16卷 第1期   页码 139-149 doi: 10.1007/s11684-021-0835-8

摘要： The CD19-targeting bispecific T-cell engager blinatumomab has shown remarkable efficacy in patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia. However, several studies showed that blinatumomab has a short plasma half-life due to its low molecular weight, and thus its clinical use is limited. Furthermore, multiple trials have shown that approximately 30% of blinatumomab-relapsed cases are characterized by CD19 negative leukemic cells. Here, we design and characterize two novel antibodies, A-319 and A-2019. Blinatumomab and A-319 are CD3/CD19 bispecific antibodies with different molecular sizes and structures, and A-2019 is a novel CD3/CD19/CD20 trispecific antibody with an additional anti-CD20 function. Our in vitro, ex vivo, and in vivo experiments demonstrated that A-319 and A-2019 are potent antitumor agents and capable of recruiting CD3 positive T cells, enhancing T-cell function, mediating B-cell depletion, and eventually inhibiting tumor growth in Raji xenograft models. The two molecules are complementary in terms of efficacy and specificity profile. The activity of A-319 demonstrated superior to that of A-2019, whereas A-2019 has an additional capability to target CD20 in cells missing CD19, suggesting its potential function against CD19 weak or negative CD20 positive leukemic cells.

关键词： B-cell acute lymphoblastic leukemia     bispecific antibody     trispecific antibody     CD19     CD20    

HTML PDF 收藏

tumor microenvironment contributes to tumor progression in diffuse large B-cell lymphoma upon anti-CD19chimeric antigen receptor T therapy

《医学前沿（英文）》 2023年 第17卷 第4期   页码 699-713 doi: 10.1007/s11684-022-0972-8

摘要： Anti-CD19 chimeric antigen receptor (CAR)-T cell therapy has achieved 40%–50% long-term complete response in relapsed or refractory diffuse large B-cell lymphoma (DLBCL) patients. However, the underlying mechanism of alterations in the tumor microenvironments resulting in CAR-T cell therapy failure needs further investigation. A multi-center phase I/II trial of anti-CD19 CD28z CAR-T (FKC876, ChiCTR1800019661) was conducted. Among 22 evaluable DLBCL patients, seven achieved complete remission, 10 experienced partial remissions, while four had stable disease by day 29. Single-cell RNA sequencing results were obtained from core needle biopsy tumor samples collected from long-term complete remission and early-progressed patients, and compared at different stages of treatment. M2-subtype macrophages were significantly involved in both in vivo and in vitro anti-tumor functions of CAR-T cells, leading to CAR-T cell therapy failure and disease progression in DLBCL. Immunosuppressive tumor microenvironments persisted before CAR-T cell therapy, during both cell expansion and disease progression, which could not be altered by infiltrating CAR-T cells. Aberrant metabolism profile of M2-subtype macrophages and those of dysfunctional T cells also contributed to the immunosuppressive tumor microenvironments. Thus, our findings provided a clinical rationale for targeting tumor microenvironments and reprogramming immune cell metabolism as effective therapeutic strategies to prevent lymphoma relapse in future designs of CAR-T cell therapy.

关键词： anti-CD19 chimeric antigen receptor T     immunotherapy     diffuse large B cell lymphoma     tumor microenvironment     tumor-associated macrophage     metabolism    

HTML PDF 收藏

Phase I study of CBM.CD19 chimeric antigen receptor T cell in the treatment of refractory diffuse large

《医学前沿（英文）》 2022年 第16卷 第2期   页码 285-294 doi: 10.1007/s11684-021-0843-8

摘要： Anti-CD19 chimeric antigen receptor (CAR) T cell therapy has shown impressive efficacy in treating B-cell malignancies. A single-center phase I dose-escalation study was conducted to evaluate the safety and efficacy of T cells transduced with CBM.CD19 CAR, a second-generation anti-CD19 CAR bearing 4-1BB costimulatory molecule, for the treatment of patients with refractory diffuse large B-cell lymphoma (DLBCL). Ten heavily treated patients with refractory DLBCL were given CBM.CD19 CAR-T cell (C-CAR011) treatment. The overall response rate was 20% and 50% at 4 and 12 weeks after the infusion of C-CAR011, respectively, and the disease control rate was 60% at 12 weeks after infusion. Treatment-emergent adverse events occurred in all patients. The incidence of cytokine release syndrome in all grades and grade≥3 was 90% and 0, respectively, which is consistent with the safety profile of axicabtagene ciloleucel and tisagenlecleucel. Neurotoxicity or other dose-limiting toxicities was not observed in any dose cohort of C-CAR011 therapy. Antitumor efficacy was apparent across dose cohorts. Therefore, C-CAR011 is a safe and effective therapeutic option for Chinese patients with refractory DLBCL, and further large-scale clinical trials are warranted.

关键词： CAR-T cell therapy     refractory diffuse large B-cell lymphoma     cytokine release syndrome     dose-limiting toxicity    

HTML PDF 收藏

供体来源的CD19靶向T细胞输注可以消除异基因造血干细胞移植后对供者淋巴细胞无反应的急性B淋巴细胞白血病微小残留病 Article

程翼飞, 陈育红, 闫晨华, 王昱, 赵翔宇, 陈瑶, 韩伟, 许兰平, 张晓辉, 刘开彦, 王莎莎, 张隆基, 肖磊, 黄晓军

《工程（英文）》 2019年 第5卷 第1期   页码 150-155 doi: 10.1016/j.eng.2018.12.006

摘要： 虽然供体来源的CD19 导向嵌合抗原受体（chimeric antigen receptor-modified，CAR）修饰T 细胞（CART19）可能治愈白血病，但输注此类细胞的效率与安全性尚未在经过在2014 年9 月至2018 年2 月期间，6 名患者均一次或多次输注了HSCT 供者提供的CD19 导向CAR 修饰T 细胞。

关键词： 供体来源的CD19靶向T细胞输注     造血干细胞移植     急性B淋巴细胞白血病     微小残留病    

HTML PDF 收藏

may affect the survival of patients with relapsed or refractory non-Hodgkin lymphoma after chimeric antigen

Lili Zhou, Ping Li, Shiguang Ye, Xiaochen Tang, Junbang Wang, Jie Liu, Aibin Liang

《医学前沿（英文）》 2020年 第14卷 第6期   页码 786-791 doi: 10.1007/s11684-020-0751-3

摘要： Factors associated with complete and durable remissions after anti-CD19 chimeric antigen receptor T (CAR-T) cell immunotherapy for relapsed or refractory non-Hodgkin lymphoma (r/r NHL) have not been well characterized. In this study, we found that the different sites of extranodal involvement may affect response, overall survival (OS), and progression-free survival (PFS) in patients with r/r NHL treated with anti-CD19 CAR-T cells. In a cohort of 32 treated patients, 12 (37.5%) and 8 (25%) patients exhibited soft tissue lymphoma and bone marrow (BM) infiltrations, respectively, and 13 (41%) patients exhibited infiltration at other sites. The factors that may affect prognosis were identified through multivariable analysis. As an independent risk factor, soft tissue infiltration was the only factor significantly correlated with adverse prognosis ( <0.05), whereas other factors did not reach statistical significance. Furthermore, the site of extranodal tumor infiltration significantly and negatively affected OS and PFS in patients with r/r NHL treated with anti-CD19 CAR-T cell therapy. PFS and OS in patients with BM involvement were not significantly different from those of patients with lymph node involvement alone. Thus, anti-CD19 CAR-T cell therapy may improve the prognosis of patients with BM infiltration.

关键词： anti-CD19 chimeric antigen receptor T cell     soft tissue     bone marrow     relapsed or refractory non-Hodgkin lymphoma    

HTML PDF 收藏

Chimeric antigen receptor T-cell therapy: a promising treatment modality for relapsed/refractory mantle

Ping Li, Ningxin Dong, Yu Zeng, Jie Liu, Xiaochen Tang, Junbang Wang, Wenjun Zhang, Shiguang Ye, Lili Zhou, Alex Hongsheng Chang, Aibin Liang

《医学前沿（英文）》 2020年 第14卷 第6期   页码 811-815 doi: 10.1007/s11684-020-0740-6

摘要： Mantle cell lymphoma (MCL) is a distinct histological type of B-cell lymphoma with a poor prognosis. Several agents, such as proteasome inhibitors, immunomodulatory drugs, and inhibitors of B cell lymphoma-2 and Bruton’s tyrosine kinase have shown efficacy for relapsed or refractory (r/r) MCL but often have short-term responses. Chimeric antigen receptor (CAR) T-cell therapy has emerged as a novel treatment modality for r/r non-Hodgkin’s lymphoma. However, long-term safety and tolerability associated with CAR T-cell therapy are not defined well, especially in MCL. In this report, we described a 70-year-old patient with r/r MCL with 48-month duration of follow-up who achieved long-term remission after CAR T-cell therapy. CAR T-cell-related toxicities were also mild and tolerated well even in this elderly patient. This report suggested that CAR T-cell therapy is a promising treatment modality for patients with MCL, who are generally elderly and have comorbid conditions.

关键词： anti-CD19 chimeric antigen receptor T cells     mantle cell lymphoma     relapsed or refractory     long-term follow-up    

HTML PDF 收藏

Serum carbohydrate antigen (CA) 19-9 as a prognostic factor in cholangiocarcinoma: A meta-analysis

Shang-Long LIU, Zi-Fang SONG, Qing-Gang HU, Shao-Bo HU, Jun LI, Qi-Chang ZHENG, Duo SHAN,

《医学前沿（英文）》 2010年 第4卷 第4期   页码 457-462 doi: 10.1007/s11684-010-0240-1

摘要： This study was performed to determine the prognostic role of preoperative serum carbohydrate antigen (CA) 19-9 levels in the survival of patients with cholangiocarcinoma. Articles published up to June 1, 2010 that evaluated preoperative CA19-9 levels and the prognosis of cholangiocarcinoma were collected for meta-analysis. The required information for calculating individual relative risk (RR) was extracted from the studies, and a combined overall RR was estimated. Nine eligible studies were included. One study dealt with extra-hepatic cholangiocarcinoma, while the other eight studies analyzed intra-hepatic cholangiocarcinoma. The mean methodological quality score was 74.1%, ranging from 65.5% to 82.5%. The overall RR for the nine studies was 1.28 (95% confidence interval= 1.10–1.46), and the Z-score for overall effect was 13.83 (<0.001). The association between serum CA19-9 level and lymph node involvement was also assessed. The combined RR was 1.471 (95% confidence interval= 0.411–5.264) and Z-score for overall effect was 0.59 ( = 0.553). CA19-9 levels were associated significantly with the prognosis of patients with cholangiocarcinoma. This meta-analysis shows that elevation of preoperative CA19-9 levels is correlated with a poor prognosis of patients with cholangiocarcinoma. However, larger scale and randomized studies are needed to draw a more substantive conclusion.

关键词： cholangiocarcinoma     prognostic factors     serum carbohydrate antigen 19-9    

HTML PDF 收藏

CD176 single-chain variable antibody fragment inhibits the adhesion of cancer cells to endothelial cells

null

《医学前沿（英文）》 2016年 第10卷 第2期   页码 204-211 doi: 10.1007/s11684-016-0443-1

摘要：

CD176 (Thomsen-Friedenreich antigen) is a tumor-associated carbohydrate epitope (glycotope) functionally involved in blood spread and liver metastasis of cancer cells by mediating the adhesion of cancer cells to endothelial cells and hepatocytes, respectively. CD176 could be a promising target for antitumor immunotherapy. We applied B lymphocytes obtained from mice immunized with CD176 antigen and constructed a phage display library. A positive clone of CD176 single-chain variable antibody fragment (scFv) was successfully screened from this library. The CD176 scFv was expressed in Escherichia coli and purified. The purified scFv can bind to the natural CD176 expressed on the surface of cancer cells. Furthermore, the CD176 scFv inhibits the adhesion of CD176+ cancer cells to endothelial cells and hepatocytes. This CD176 scFv provides a basis for future development of recombinant CD176-specific antibodies that can be used in therapeutic application.

关键词： CD176     Thomsen-Friedenreich antigen     scFv     cancer     therapy     adhesion     metastasis    

HTML PDF 收藏

外泌体CD44与整合素α6β4结合激活宿主细胞重塑肿瘤微环境促进胰腺癌恶性转移 Article

牟为, 许亚婕, 顾鹏飞, 王文斌, 李井泉, 葛阳, 王慧

《工程（英文）》 2021年 第7卷 第10期   页码 1415-1425 doi: 10.1016/j.eng.2020.08.013

摘要： 我们的研究发现，由外泌体传递的跨膜糖蛋白CD44通过重编程肿瘤微环境，参与了胰腺癌的转移过程。CD44与整合素α6β4相互作用形成复合物，激活细胞内骨架蛋白及其信号通路，进而调控Src和Ras信号级联反应，促进肿瘤细胞的运动。值得注意的是，我们还证明了CD44-α6β4复合物可以通过外泌体的旁分泌作用传递到靶区。肝细胞选择性摄取具有高表达CD44的肿瘤外泌体，并通过刺激细胞因子、促炎因子和生长因子产生转移前生态位，最终支持肿瘤转移。我们的研究结果表明，外泌体CD44有可能作为胰腺癌临床诊断和治疗的生物标志物。

关键词： 胰腺癌     靶向器官转移     外泌体     细胞间交流     CD44    

HTML PDF 收藏

基于抗原和聚合酶链式反应的组合策略对模拟社区内遏制COVID-19传播效果的定量分析 Article

黄蔷如, 孙艳侠, 贾萌萌, 张婷, 陈方圆, 姜明月, 王晴, 冯录召, 杨维中

《工程（英文）》 2023年 第28卷 第9期   页码 234-242 doi: 10.1016/j.eng.2023.01.004

摘要：

新型冠状病毒肺炎（coronavirus disease 2019, COVID-19）病例数量持续增加，这使得许多国家的医疗系统不堪重负并导致超额死亡对感染人群进行检测仍然是遏制COVID-19疫情、延缓疾病的传播以及拉平疫情流行曲线的关键策略。我们开发了一个随机的、基于agent的、离散时间的易感者—潜隐者—感染者—康复者模型来模拟COVID-19在社区内的传播，评估了三个不同强度级别的检测策略与COVID-19传播之间的关联。

关键词： COVID-19     抗原检测     PCR核酸检测     检测策略    

HTML PDF 收藏

从药物开发的角度看工程化T细胞疗法 Review

Fang Chen, Joseph A. Fraietta, Carl H. June, 许中伟, J. Joseph Melenhorst, Simon F. Lacey

《工程（英文）》 2019年 第5卷 第1期   页码 140-149 doi: 10.1016/j.eng.2018.11.010

摘要： 例如，经基因修饰后，T 细胞可表达嵌合抗原受体（chimeric antigen receptor，CAR），使其能够识别并杀死肿瘤细胞，并形成一个记忆库，准备回击持续存在的恶性细胞。抗CD19 嵌合抗原受体T 细胞（CAR T cells，CART19）对某些恶性肿瘤具有显著的临床疗效。随着制药行业的主要参与者联手使这种新型“活药物”商业化，以CART19 为例，与传统药物相比，研究其开发过程中的相似性和差异性非常有用。本文综述了基于生物标志物的分析方法在优化CAR结构、临床前研究和临床疗效评价、不良反应（AE）和CART19 细胞动力学方面的应用。我们相信，就像胂凡纳明的发现开创了合成药物时代一样，CART19 的成功能够带来其他工程化T 细胞疗法的发展。

关键词： 工程化T细胞疗法     嵌合抗原受体     药物开发过程     生物标志物     CAR19     CART19    

HTML PDF 收藏

Clinical significance of CD34+CD117dim/CD34+CD117bri myeloblast-associated

Xueping Li, Yuting Dai, Bing Chen, Jinyan Huang, Saijuan Chen, Lu Jiang

《医学前沿（英文）》 2021年 第15卷 第4期   页码 608-620 doi: 10.1007/s11684-021-0836-7

摘要： t(8;21)(q22;q22) acute myeloid leukemia (AML) is a highly heterogeneous hematological malignancy with a high relapse rate in China. Two leukemic myeloblast populations (CD34 CD117 and CD34 CD117 ) were previously identified in t(8;21) AML, and CD34 CD117 cell proportion was determined as an independent factor for this disease outcome. Here, we examined the impact of CD34 CD117 /CD34 CD117 myeloblast-associated gene expression on t(8;21) AML clinical prognosis. In this study, 85 patients with t(8;21) AML were enrolled. The mRNA expression levels of CD34 CD117 -associated genes ( , , and ) and CD34 CD117 -associated genes ( , , and ) were measured using quantitative reverse transcription PCR. Associations between gene expression and clinical outcomes were determined using Cox regression models. Results showed that patients with high , , or expression had significantly inferior overall survival (OS), whereas those with high or expression showed relatively favorable prognosis. Univariate analysis revealed that CD19, CD34 CD117 proportion, mutation, minimal residual disease (MRD), and expression levels of , , , and were associated with OS. Multivariate analysis indicated that mutation, MRD and and expression levels were independent prognostic variables for OS. Identifying the clinical relevance of CD34 CD117 /CD34 CD117 myeloblast-associated gene expression may provide new clinically prognostic markers for t(8;21) AML.

关键词： t(8     21)(q22     q22) AML     CD34+CD117dim/ CD34+CD117bri cell population     gene expression     prognosis    

HTML PDF 收藏

Comparisons in subcellular and biochemical behaviors of cadmium between low-Cd and high-Cd accumulation

Meng XUE, Yihui ZHOU, Zhongyi YANG, Biyun LIN, Jiangang YUAN, Shanshan WU

《环境科学与工程前沿（英文）》 2014年 第8卷 第2期   页码 226-238 doi: 10.1007/s11783-013-0582-4

摘要： Subcellular distributions and chemical forms of cadmium (Cd) in the leaves, stems and roots were investigated in low-Cd accumulation cultivars and high-Cd accumulation cultivars of pakchoi ( L.). Root cell wall played a key role in limiting soil Cd from entering the protoplast, especially in the low-Cd cultivars. The high-Cd cultivars had significantly higher leaf and stem Cd concentrations than the low-Cd cultivars in cell wall fraction, chloroplast/trophoplast fraction, organelle fraction and soluble fraction. In low-Cd cultivars, which were more sensitive and thus had greater physiological needs of Cd detoxification than high-Cd cultivars, leaf vacuole sequestrated higher proportions of Cd. Cd in the form of pectate/protein complexes (extracted by 1 mol·L NaCl) played a decisive role in Cd translocation from root to shoot, which might be one of the mechanisms that led to the differences in shoot Cd accumulation between the two types of cultivars. Furthermore, the formation of Cd-phosphate complexes (extracted by 2% HAc) was also involved in Cd detoxification within the roots of pakchoi under high Cd stress, suggesting that the mechanisms of Cd detoxification might be different between low- and high-Cd cultivars.

关键词： cadmium (Cd)     low-Cd cultivar     pakchoi (Brassica chinensis L.)     subcellular distribution     chemical forms    

HTML PDF 收藏

Cultivars and oil extraction techniques affect Cd/Pb contents and health risks in oil of rapeseed grownon Cd/Pb-contaminated farmland

《环境科学与工程前沿（英文）》 2023年 第17卷 第7期 doi: 10.1007/s11783-023-1687-z

摘要：

● Organic solvent extracted fewer Cd/Pb in rapeseed oil than physical pressing.

关键词： Rapeseed oil     Oil extraction technologies     Human health risk assessment     Cd/Pb-contaminated farmland     Substitute planting    

HTML PDF 收藏

标题 作者 时间 类型 操作

Tumor-derived exosomes induce initial activation by exosomal CD19 antigen but impair the function ofCD19-specific CAR T-cells via TGF-β signaling

期刊论文

Preclinical characterization and comparison between CD3/CD19 bispecific and novel CD3/CD19/CD20 trispecific

期刊论文

tumor microenvironment contributes to tumor progression in diffuse large B-cell lymphoma upon anti-CD19chimeric antigen receptor T therapy

期刊论文

Phase I study of CBM.CD19 chimeric antigen receptor T cell in the treatment of refractory diffuse large

期刊论文

供体来源的CD19靶向T细胞输注可以消除异基因造血干细胞移植后对供者淋巴细胞无反应的急性B淋巴细胞白血病微小残留病

程翼飞, 陈育红, 闫晨华, 王昱, 赵翔宇, 陈瑶, 韩伟, 许兰平, 张晓辉, 刘开彦, 王莎莎, 张隆基, 肖磊, 黄晓军

期刊论文

may affect the survival of patients with relapsed or refractory non-Hodgkin lymphoma after chimeric antigen

Lili Zhou, Ping Li, Shiguang Ye, Xiaochen Tang, Junbang Wang, Jie Liu, Aibin Liang

期刊论文

Chimeric antigen receptor T-cell therapy: a promising treatment modality for relapsed/refractory mantle

Ping Li, Ningxin Dong, Yu Zeng, Jie Liu, Xiaochen Tang, Junbang Wang, Wenjun Zhang, Shiguang Ye, Lili Zhou, Alex Hongsheng Chang, Aibin Liang

期刊论文

Serum carbohydrate antigen (CA) 19-9 as a prognostic factor in cholangiocarcinoma: A meta-analysis

Shang-Long LIU, Zi-Fang SONG, Qing-Gang HU, Shao-Bo HU, Jun LI, Qi-Chang ZHENG, Duo SHAN,

期刊论文

CD176 single-chain variable antibody fragment inhibits the adhesion of cancer cells to endothelial cells

null

期刊论文

外泌体CD44与整合素α6β4结合激活宿主细胞重塑肿瘤微环境促进胰腺癌恶性转移

牟为, 许亚婕, 顾鹏飞, 王文斌, 李井泉, 葛阳, 王慧

期刊论文

基于抗原和聚合酶链式反应的组合策略对模拟社区内遏制COVID-19传播效果的定量分析

黄蔷如, 孙艳侠, 贾萌萌, 张婷, 陈方圆, 姜明月, 王晴, 冯录召, 杨维中

期刊论文

从药物开发的角度看工程化T细胞疗法

Fang Chen, Joseph A. Fraietta, Carl H. June, 许中伟, J. Joseph Melenhorst, Simon F. Lacey

期刊论文

Clinical significance of CD34+CD117dim/CD34+CD117bri myeloblast-associated

Xueping Li, Yuting Dai, Bing Chen, Jinyan Huang, Saijuan Chen, Lu Jiang

期刊论文

Comparisons in subcellular and biochemical behaviors of cadmium between low-Cd and high-Cd accumulation

Meng XUE, Yihui ZHOU, Zhongyi YANG, Biyun LIN, Jiangang YUAN, Shanshan WU

期刊论文

Cultivars and oil extraction techniques affect Cd/Pb contents and health risks in oil of rapeseed grownon Cd/Pb-contaminated farmland

期刊论文