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Soluble triggering receptor expressed on myeloid cell-1 (sTREM-1): a potential biomarker for the diagnosis

Changlin Cao, Jingxian Gu, Jingyao Zhang

《医学前沿（英文）》 2017年 第11卷 第2期   页码 169-177 doi: 10.1007/s11684-017-0505-z

摘要： Sensitive and useful biomarkers for the diagnosis and prognosis of infectious diseases have been widely developed. An example of these biomarkers is triggering receptor expressed on myeloid cell-1 (TREM-1), which is a cell surface receptor expressed on monocytes/macrophages and neutrophils. TREM-1 amplifies inflammation by activating the TREM-1/DAP12 pathway. This pathway is triggered by the interaction of TREM-1 with ligands or stimulation by bacterial lipopolysaccharide. Consequently, pro-inflammatory cytokines and chemokines are secreted. Soluble TREM-1 (sTREM-1) is a special form of TREM-1 that can be directly tested in human body fluids and well-known biomarker for infectious diseases. sTREM-1 level can be potentially used for the early diagnosis and prognosis prediction of some infectious diseases, including infectious pleural effusion, lung infections, sepsis, bacterial meningitis, viral infections (e.g., Crimean Congo hemorrhagic fever and dengue fever), fungal infections (e.g., infection), and burn-related infections. sTREM-1 is a more sensitive and specific biomarker than traditional indices, such as C-reactive protein and procalcitonin levels, for these infectious diseases. Therefore, sTREM-1 is a feasible biomarker for the targeted therapy and rapid and early diagnosis of infectious diseases.

关键词： soluble triggering receptor expressed on myeloid cells-1     infectious diseases     diagnosis and prognosis     biomarker    

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4-1BBL expressed by eukaryotic cells activates immune cells and suppresses the progression of murine

Hui QIU, Hui ZHANG, Zuohua FENG

《医学前沿（英文）》 2009年 第3卷 第1期   页码 20-25 doi: 10.1007/s11684-009-0006-9

摘要： The interaction by co-stimulatory molecules 4-1BB and 4-1BB ligand (4-1BBL) plays an important role in the activation, proliferation and differentiation of T lymphocytes. The function of 4-1BB/4-1BBL expressed by the immune cells has been the focus for many tumor immunotherapy efforts. In this study, 4-1BBL was expressed in non-immune cells and non-tumor cells, and the role of 4-1BBL in lymphocyte activation and tumor suppression was investigated. The plasmid p4-1BBL containing the full length of mouse 4-1BBL cDNA sequence was constructed, and the plasmid was transfected into baby hamster kidney (BHK) cells and murine muscle cells by means of lipofectin-mediated or naked plasmid DNA injection into the muscle directly. The study demonstrated that the molecule 4-1BBL expressed by BHK cells could enhance the proliferation and cytotoxicity of lymphocytes, and it could increase the expression level of IL-2 and IFN-γ. The treatment with plasmid p4-1BBL revealed that the number of CD8 T cells in the peri-tumoral tissue increased markedly, and the growth rate of the tumor was significantly lower than that of control group. These findings suggest that expression of 4-1BBL by normal cells in the tumor microenvironment can enhance the proliferation and other functions of T lymphocytes. This therapeutic method may provide a promising approach for tumor immunotherapy.

关键词： 4-1BB ligand     tumor immunotherapy     tumor microenvironment    

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Chimeric antigen receptor T cell therapies for acute myeloid leukemia

Bin Gu, Jianhong Chu, Depei Wu

《医学前沿（英文）》 2020年 第14卷 第6期   页码 701-710 doi: 10.1007/s11684-020-0763-z

摘要： Abstract Chimeric antigen receptor T cell (CAR T) therapies have achieved unprecedented efficacy in B-cell tumors, prompting scientists and doctors to exploit this strategy to treat other tumor types. Acute myeloid leukemia (AML) is a group of heterogeneous myeloid malignancies. Relapse remains the main cause of treatment failure, especially for patients with intermediate or high risk stratification. Allogeneic hematopoietic stem cell transplantation could be an effective therapy because of the graft-versus-leukemia effect, which unfortunately puts the patient at risk of serious complications, such as graft-versus-host disease. Although the identification of an ideal target antigen for AML is challenging, CAR T therapy remains a highly promising strategy for AML patients, particularly for those who are ineligible to receive a transplantation or have positive minimal residual disease. In this review, we focus on the most recent and promising advances in CAR T therapies for AML.

关键词： acute myeloid leukemia     CAR T     immunotherapy    

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Plasma soluble C-type lectin-like receptor-2 is associated with the risk of coronary artery disease

Min Fei, Li Xiang, Xichen Chai, Jingchun Jin, Tao You, Yiming Zhao, Changgeng Ruan, Yiwen Hao, Li Zhu

《医学前沿（英文）》 2020年 第14卷 第1期   页码 81-90 doi: 10.1007/s11684-019-0692-x

摘要： Accumulating evidence suggests that C-type lectin-like receptor-2 (CLEC-2) plays an important role in atherothrombosis. In this case-control study, we investigated the association between CLEC-2 and incidence of coronary artery disease (CAD). A total of 216 patients, including 14 cases of stable angina pectoris (SAP, non-ACS) and 202 cases of acute coronary syndrome (ACS), and 89 non-CAD control subjects were enrolled. Plasma levels of soluble CLEC-2 (sCLEC-2) were measured using the enzyme-linked immunosorbent assay (ELISA). Compared with the control group (65.69 (55.36–143.22) pg/mL), the plasma levels of sCLEC-2 were significantly increased in patients with CAD (133.67 (88.76–220.09) pg/mL) and ACS (134.16 (88.88–225.81) pg/mL). The multivariate adjusted odds ratios (95% confidence interval) of CAD reached 2.01 (1.52–2.66) ( <0.001) for each 1-quartile increase in sCLEC-2. Restricted cubic splines showed a positive dose-response association between sCLEC2 and CAD incidence ( <0.001). The addition of sCLEC-2 to conventional risk factors improved the C statistic (0.821 vs. 0.761, = 0.004) and reclassification ability (net reclassification improvement: 57.45%, <0.001; integrated discrimination improvement: 8.27%, <0.001) for CAD. In conclusion, high plasma sCLEC-2 is independently associated with CAD risk, and the prognostic value of sCLEC-2 may be evaluated in future prospective studies.

关键词： soluble C-type lectin-like receptor-2     coronary artery disease     risk factor    

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Alternative splicing of inner-ear-expressed genes

null

《医学前沿（英文）》 2016年 第10卷 第3期   页码 250-257 doi: 10.1007/s11684-016-0454-y

摘要：

Alternative splicing plays a fundamental role in the development and physiological function of the inner ear. Inner-ear-specific gene splicing is necessary to establish the identity and maintain the function of the inner ear. For example, exon 68 of Cadherin 23 (Cdh23) gene is subject to inner-ear-specific alternative splicing, and as a result, Cdh23(+68) is only expressed in inner ear hair cells. Alternative splicing along the tonotopic axis of the cochlea contributes to frequency tuning, particularly in lower vertebrates, such as chickens and turtles. Differential splicing of Kcnma1, which encodes for the α subunit of the Ca2+-activated K+ channel (BK channel), has been suggested to affect the channel gating properties and is important for frequency tuning. Consequently, deficits in alternative splicing have been shown to cause hearing loss, as we can observe in Bronx Waltzer (bv) mice and Sfswap mutant mice. Despite the advances in this field, the regulation of alternative splicing in the inner ear remains elusive. Further investigation is also needed to clarify the mechanism of hearing loss caused by alternative splicing deficits.

关键词： alternative splicing     inner ear     hearing loss     hair cells    

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Recent advances in myeloid-derived suppressor cell biology

Mahmoud Mohammad Yaseen, Nizar Mohammad Abuharfeil, Homa Darmani, Ammar Daoud

《医学前沿（英文）》 2021年 第15卷 第2期   页码 232-251 doi: 10.1007/s11684-020-0797-2

摘要： In recent years, studying the role of myeloid-derived suppressor cells (MDSCs) in many pathological inflammatory conditions has become a very active research area. Although the role of MDSCs in cancer is relatively well established, their role in non-cancerous pathological conditions remains in its infancy resulting in much confusion. Our objectives in this review are to address some recent advances in MDSC research in order to minimize such confusion and to provide an insight into their function in the context of other diseases. The following topics will be specifically focused upon: (1) definition and characterization of MDSCs; (2) whether all MDSC populations consist of immature cells; (3) technical issues in MDSC isolation, estimation and characterization; (4) the origin of MDSCs and their anatomical distribution in health and disease; (5) mediators of MDSC expansion and accumulation; (6) factors that determine the expansion of one MDSC population over the other; (7) the Yin and Yang roles of MDSCs. Moreover, the functions of MDSCs will be addressed throughout the text.

关键词： non-human primates (rhesus macaques)     myeloid-derived pro-inflammatory cells (MDPCs)     autoimmune disorders     alloimmune responses     pregnancy     mature MDSCs     multiple sclerosis     Yin-Yang law of MDSCs    

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Influence of β-elemene on the secretion of angiotensin II and expression of AT1R in hepatic stellatecells

Ling YANG, Rui ZHU, Qingjing ZHU, Dan DAN, Jin YE, Keshu XU, Xiaohua HOU

《医学前沿（英文）》 2009年 第3卷 第1期   页码 36-40 doi: 10.1007/s11684-009-0020-y

摘要： This study aims to investigate the influence of β-elemene on the secretion of angiotensin II (ANG II) and the expression of angiotensin receptor type 1 (AT1R) in hepatic stellate cells (HSCs). , HSC-T6 were cultured for 24 hours and then treated with different doses of β-elemene (2.5, 5 and 10 mg/L). A control group was also set up. The secretion of ANG II in the supernatant was detected by radioimmunoassay. The mRNA expression of AT1R at 4, 12 and 24 h after treatment was detected by reverse transcription-polymerase chain reaction (RT-PCR), respectively. The protein expression of AT1R was detected by western blot. At the 4th h, the ANG II secretion in the supernatant was significantly inhibited by 10 mg/L β-elemene compared with the control group ( <0.05), while 5.0 mg/L and 2.5 mg/L β-elemene had no inhibitory effect on the secretion of ANG II ( >0.05). At the time point of the 12th h, the secretion of ANG II in the supernatant treated with 10 mg/L and 5.0 mg/L β-elemene was significantly lower than the control ( <0.01, <0.05). Following the treatment with 5.0 mg/L and 2.5 mg/L β-elemene for 24 h, significant inhibition of ANG II secretion was observed ( <0.05), but 10 mg/L β-elemene had no such effect. β-elemene significantly reduced the amount of AT1R mRNA in HSCs after the treatment for 4, 12, and 24 h in a dose-dependent manner. The expression of AT1R protein also decreased after the treatment with β-elemene for 24 h. β-elemene can inhibit the secretion of ANG II and the gene and protein expression of AT1R, which may be the mechanism by which β-elemene prevents the progress of hepatic fibrosis.

关键词： liver cirrhosis     beta-elemene     hepatic stellate cells     angiotensin II     receptor     angiotensin     type 1    

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expression pattern of mutations coordinated by target repression and promoter hypermethylation in acute myeloid

《医学前沿（英文）》 2022年 第16卷 第4期   页码 627-636 doi: 10.1007/s11684-020-0815-4

摘要： Runt-related transcription factor 1 (RUNX1) is an essential regulator of normal hematopoiesis. Its dysfunction, caused by either fusions or mutations, is frequently reported in acute myeloid leukemia (AML). However, RUNX1 mutations have been largely under-explored compared with RUNX1 fusions mainly due to their elusive genetic characteristics. Here, based on 1741 patients with AML, we report a unique expression pattern associated with RUNX1 mutations in AML. This expression pattern was coordinated by target repression and promoter hypermethylation. We first reanalyzed a joint AML cohort that consisted of three public cohorts and found that RUNX1 mutations were mainly distributed in the Runt domain and almost mutually exclusive with NPM1 mutations. Then, based on RNA-seq data from The Cancer Genome Atlas AML cohort, we developed a 300-gene signature that significantly distinguished the patients with RUNX1 mutations from those with other AML subtypes. Furthermore, we explored the mechanisms underlying this signature from the transcriptional and epigenetic levels. Using chromatin immunoprecipitation sequencing data, we found that RUNX1 target genes tended to be repressed in patients with RUNX1 mutations. Through the integration of DNA methylation array data, we illustrated that hypermethylation on the promoter regions of RUNX1-regulated genes also contributed to dysregulation in RUNX1-mutated AML. This study revealed the distinct gene expression pattern of RUNX1 mutations and the underlying mechanisms in AML development.

关键词： RUNX1     gene mutation     acute myeloid leukemia     transcriptional repression     DNA methylation    

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Ultraviolet-B induced expression of hypoxia-inducible factor 1α, transferrin receptor through EGFR/PI3K/AKT/DEC1 pathway

LI Yanhua, BI Zhigang

《医学前沿（英文）》 2007年 第1卷 第1期   页码 79-86 doi: 10.1007/s11684-007-0016-4

摘要： The aim of this research was to explore the effects and signaling pathway of ultraviolet-B (UVB) irradiation on the expression of hypoxia-inducible factor 1α (HIF-1α) and transferrin receptor (TfR). HIF-1α protein was measured by Western blot method. Expressions of epidermal growth factor receptor (EGFR), phosphor-EGF-R and TfR after UVB irradiation were determined with flow cytometry. After UVB irradiation, mRNA levels of HIF-1α and TfR were detected by real time-PCR. Results showed that compared with control groups, UVB was able to induce HIF1α and TfR protein expression in a dose- and time-dependent manner in HaCat cells (<0.05). TfR mRNA was expressed in a dose-dependent manner and reached a peak at the 8th hour in HaCat cells (<0.05) whereas HIF-1α mRNA expression was not affected by UVB treatment (>0.05). The EGFR/PI3K/AKT signaling pathway was required for the induction of HIF-1α and TfR expression induced by UVB. UVB induced activation of EGFR in HaCat cells and EGFR regulated expression of TfR and HIF-1α. EGFR (-/-) MEF did not increase the HIF1 expression following UVB irradiation (>0.05). In contrast, EGFR (+/+) MEF strongly enhanced HIF1α expression after UVB irradiation (<0.05). PD153035, a selective inhibitor of EGFR tyrosine kinase, inhibited the TfR protein expression in UVB-treated cells in a dose-dependent manner (P<0.05). PI3K inhibitors, LY294002 and wortmannin, inhibited HIF-1? and TfR expressions induced by UVB (P<0.05). The DEC1 (-/-) Ha-Cat cells did not increase their TfR and HIF-1α expressions following UVB irradiation (>0.05). In contrast, DEC1 (+/+) HaCat cells strongly enhanced TfR and HIF-1? protein expression after UVB irradiation (P<0.05). We conclude that UVB induces TfR and HIF-1αexpressions via EGFR/PI3K/AKT/DEC1 signaling pathway.
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Effect of bradykinin on bradykinin-B2 receptor in rat aortic vascular smooth muscle cells and the involved

Wen YAN MD, Min FENG MD, Pei-Hua WANG MD, Dao-Wen WANG MD,

《医学前沿（英文）》 2010年 第4卷 第2期   页码 225-228 doi: 10.1007/s11684-010-0003-z

摘要： The aim of this paper is to study the effect of bradykinin (BK) on bradykinin-B2 receptor as well as the possible involved signal transduction pathways in cultured rat aortic vascular smooth muscle cells (VSMCs). Rat aortic VSMCs were cultured. Cells after 4–6 passages were used in the experiment. VSMCs were incubated with BK, BK+ B2 receptor inhibitor (HOE-140), BK+ MEK inhibitor (PD98059), BK+ mitogen-activated protein kinase (MAPK) inhibitor (apigenin), BK+ phosphoinositide 3-kinase (PI3K) inhibitor (LY294002), and BK+ Akt inhibitor to evaluate the expression of B2 receptor and phosphorylation of signaling molecules MAPK, Akt, and PI3K by Western blot. (1) BK markedly up-regulated the expression of B2 receptor in VSMC. (2) Apigenin, PD98059, Akt inhibitor, and LY294002 inhibited up-regulation of B2 receptor induced by BK. (3) Signal transduction pathways of MAPK and PI3K were involved in the up-regulation of B2 receptor by BK mediation. Results suggest that bradykinin can up-regulate the expression of B2 receptor in VSMCs.

关键词： bradykinin     vascular smooth muscle cells     signal transduction pathways    

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Synthesis and properties of water-soluble 1,9-dialkyl-substituted BF

Dan Wu, Gonzalo Durán-Sampedro, Donal F. O’Shea

《化学科学与工程前沿（英文）》 2020年 第14卷 第1期   页码 97-104 doi: 10.1007/s11705-019-1828-x

摘要： Bis-alkylsulfonic acid and polyethylene glycol (PEG)-substituted BF azadipyrromethenes have been synthesized by an adaptable and versatile route. Only four synthetic stages were required to produce the penultimate fluorophore compounds, containing either two alcohol or two terminal alkyne substituents. The final synthetic step introduced either sulfonic acid or polyethylene glycol groups to impart aqueous solubility. Sulfonic acid groups were introduced by reaction of the bis-alcohol-substituted fluorophore with sulfur trioxide, and a double Cu(I)-catalyzed cycloaddition reaction between the bis-alkyne fluorophore and methoxypolyethylene glycol azide yielded a neutral bis-pegylated derivative. Both fluorophores exhibited excellent near-infrared (NIR) photophysical properties in methanol and aqueous solutions. Live cell microscopy imaging revealed efficient uptake and intracellular labelling of cells for both fluorophores. Their simple synthesis, with potential for last-step structural modifications, makes the present NIR-active azadipyrromethene derivatives potentially useful as NIR fluorescence imaging probes for live cells.

关键词： NIR-fluorophores     live cell imaging     NIR-AZA    

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Mutant DNA methylation regulators endow hematopoietic stem cells with the preleukemic stem cell property

null

《医学前沿（英文）》 2015年 第9卷 第4期   页码 412-420 doi: 10.1007/s11684-015-0423-x

摘要：

Genetic mutations are considered to drive the development of acute myeloid leukemia (AML). With the rapid progress in sequencing technologies, many newly reported genes that are recurrently mutated in AML have been found to govern the initiation and relapse of AML. These findings suggest the need to distinguish the driver mutations, especially the most primitive single mutation, from the subsequent passenger mutations. Recent research on DNA methyltransferase 3A (DNMT3A) mutations provides the first proof-of-principle investigation on the identification of preleukemic stem cells (pre-LSCs) in AML patients. Although DNMT3A mutations alone may only transform hematopoietic stem cells into pre-LSCs without causing the full-blown leukemia, the function of this driver mutation appear to persist from AML initiation up to relapse. Therefore, identifying and targeting preleukemic mutations, such as DNMT3A mutations, in AML is a promising strategy for treatment and reduction of relapse risk.

关键词： preleukemic stem cell     acute myeloid leukemia     relapse     DNMT3A    

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Gene and protein expression of proteinase-activated receptor-1, 2 in a murine model of acute graft host

Quan LI MD , Weiming LI MD , Ping ZOU MD , Jian ZHANG BM ,

《医学前沿（英文）》 2009年 第3卷 第3期   页码 309-315 doi: 10.1007/s11684-009-0043-4

摘要： Proteinase-activated receptors (PARs) are a novel subclass of seven transmembrane-spanning, G protein-coupled receptors. PAR-1 and PAR-2 are widely expressed in a variety of cells and are found to be involved in many physiological and pathological processes including inflammation and immune response. However, little is known about the function of PAR-1, 2 in acute graft host disease (GVHD). In the present study, we first detected the expression of PAR-1, 2 protein and mRNA in a murine model of acute GVHD using the methods of immunohistochemistry, Western blot and quantitative real-time polymerase chain reaction (PCR). Syngeneic hematopoietic stem cell transplantation (HSCT) mice served as controls. The relative gene expression level of PAR-1 was significantly increased in the skin, liver, small intestine of allogeneic HSCT mice (in skin: 0.039±0.013 0.008±0.002 of controls, =0.009; in liver: 0.165±0.006 0.017±0.006 of controls, =0.004; in small intestine: 0.215±0.009 0.016±0.002 of controls, =0.003), but not in the stomach, lung and kidney of allogeneic HSCT mice (>0.05). PAR-2 mRNA expression in the liver and small intestine of allogeneic HSCT mice (in liver: 0.010±0.002 0.003±0.001 of controls, =0.008; in small intestine: 0.006±0.001 0.003±0.001 of controls, =0.024) was increased significantly, but PAR-2 mRNA expression in the other organs (>0.05) was not found to be significantly elevated. PAR-1, 2 protein expression was in accordance with the mRNA expression, as shown by Western blot. Using immunohistochemistry the present study demonstrated that there was strong PAR-1, 2 immunoreactivity in the epithelial cell and vascular endothelial cell of target organs of acute GVHD. Our findings of markedly increased expression of PAR-1, 2 in target organs of acute GVHD suggest that PAR-1 and PAR-2 may play an important role in the pathogenesis of acute GVHD.

关键词： graft vs host disease     proteinase-activated receptor     murine model     hematopoietic stem cell transplantation    

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Effects of RNA interference targeting angiotensin 1a receptor on blood pressure and cardiac hypertrophy

ZHANG Jingqun, SUN Honglei, MA Yexin, WANG Daowen

《医学前沿（英文）》 2008年 第2卷 第1期   页码 19-24 doi: 10.1007/s11684-008-0005-2

摘要： The aim of this study is to investigate the effects of RNA interference (RNAi) targeting angiotensin 1a receptor (AT1a) on blood pressure and cardiac hypertrophy of rats with renovascular hypertension. Two RNAi plasmids, pAT1a-shRNA1 and pAT1a-shRNA2 each carrying a U6 promoter and an AT1a-specific shRNA-coding template sequence corresponding to the sites 928–946, 978–996 of the mRNA transcript, and a control plasmid pCon carrying a nonspecific shRNA-coding sequence were constructed. Thirty Sprague – Dawley rats with renovascular hypertension (2-kidney 1-clip) were randomly divided into 5 equal groups: Control group (without any intervention), pAT1a-shRNA1, pAT1a-shRNA2, pCon groups (with injection of the corresponding plasmid 4 mg/kg respectively into the tail vein), and valsartan group (30 mg/kg·d by gavage). Three weeks after drug administration, pAT1a-shRNA1, pAT1a-shRNA2 and valsartan respectively resulted in decrease of the tail blood pressure by (15.1 ± 5.4), (16.4 ± 8.4) and (30.6 ± 18.2) mmHg. However, the tail blood pressure increased further by about 25 mmHg in both of pCon and control groups. The carotid artery pressures of pAT1a-shRNA1, pAT1a-shRNA2 and valsartan groups were all significantly lower than those of the control and pCon groups. The ratio of left ventricle weight to body weight (LV/BW) of the rats in pAT1a-shRNA1, pAT1a-shRNA2, and valsartan groups decreased significantly than in the control group ( < 0.01), similar to those of the normal SD rats( > 0.05). Histopathological examination showed that the myocardiocytes were significantly hypertrophic and the basal membrane of the aorta was significantly thickened in the control group and such changes were alleviated in the pAT1a-shRNA1, pAT1a-shRNA2 and valsartan groups. Compared with the control group, pAT1a-shRNA1 and pAT1a-shRNA2 groups had lowered expression of AT1 receptor (in the myocardium and the thoracic aorta (all < 0.01); however, there were no significant differences in expression levels of AT1 receptor in valsartan and the control groups ( > 0.05). We conclude that RNAi targeting AT1a receptor inhibits the development of renovascular hypertension and the accompanying cardiac hypertrophy. RNAi technology may become a new strategy of gene therapy for hypertension.

关键词： therapy     Sprague     administration     cardiac hypertrophy     valsartan    

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Chimeric antigen receptor T cell targeting EGFRvIII for metastatic lung cancer therapy

Zhao Zhang, Jun Jiang, Xiaodong Wu, Mengyao Zhang, Dan Luo, Renyu Zhang, Shiyou Li, Youwen He, Huijie Bian, Zhinan Chen

《医学前沿（英文）》 2019年 第13卷 第1期   页码 57-68 doi: 10.1007/s11684-019-0683-y

摘要：

Lung cancer is the most common incident cancer and the leading cause of cancer death. In recent years, the development of tumor immunotherapy especially chimeric antigen receptor T (CAR-T) cell has shown a promising future. Epidermal growth factor receptor variant III (EGFRvIII) is a tumor-specific mutation expressed in various types of tumors and has been detected in non-small cell lung cancer with a mutation rate of 10%. Thus, EGFRvIII is a potential antigen for targeted lung cancer therapy. In this study, CAR vectors were constructed and transfected into virus-packaging cells. Then, activated T cells were infected with retrovirus harvested from stable virus-producing single clone cell lines. CAR expression on the surfaces of the T cells was detected by flow cytometry and Western blot. The function of CAR-T targeting EGFRvIII was then evaluated. The EGFRvIII-CAR vector was successfully constructed and confirmed by DNA sequencing. A stable virus-producing cell line was produced from a single clone by limited dilution. The culture conditions for the cell line, including cell density, temperature, and culture medium were optimized. After infection with retrovirus, CAR was expressed on more than 90% of the T cells. The proliferation of CAR-T cells were induced by cytokine and specific antigen in vitro. More importantly, EGFRvIII-CART specifically and efficiently recognized and killed A549-EGFRvIII cells with an effector/target ratio of 10:1 by expressing and releasing cytokines, including perforin, granzyme B, IFN-g, and TNF-α. The in vivo study indicated that the metastasis of A549-EGFRvIII cells in mice were inhibited by EGFRvIII-CART cells, and the survival of the mice was significantly prolonged with no serious side effects. EGFRvIII-CART showed significantly efficient antitumor activity against lung cancer cells expressing EGFRvIII in vivo and in vitro. Therefore, CAR-T targeting EGFRvIII is a potential therapeutic strategy in preventing recurrence and metastasis of lung cancer after surgery.

关键词： chimeric antigen receptor T cells     epidermal growth factor receptor     lung cancer     immunotherapy     tumor immunology    

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标题 作者 时间 类型 操作

Soluble triggering receptor expressed on myeloid cell-1 (sTREM-1): a potential biomarker for the diagnosis

Changlin Cao, Jingxian Gu, Jingyao Zhang

期刊论文

4-1BBL expressed by eukaryotic cells activates immune cells and suppresses the progression of murine

Hui QIU, Hui ZHANG, Zuohua FENG

期刊论文

Chimeric antigen receptor T cell therapies for acute myeloid leukemia

Bin Gu, Jianhong Chu, Depei Wu

期刊论文

Plasma soluble C-type lectin-like receptor-2 is associated with the risk of coronary artery disease

Min Fei, Li Xiang, Xichen Chai, Jingchun Jin, Tao You, Yiming Zhao, Changgeng Ruan, Yiwen Hao, Li Zhu

期刊论文

Alternative splicing of inner-ear-expressed genes

null

期刊论文

Recent advances in myeloid-derived suppressor cell biology

Mahmoud Mohammad Yaseen, Nizar Mohammad Abuharfeil, Homa Darmani, Ammar Daoud

期刊论文

Influence of β-elemene on the secretion of angiotensin II and expression of AT1R in hepatic stellatecells

Ling YANG, Rui ZHU, Qingjing ZHU, Dan DAN, Jin YE, Keshu XU, Xiaohua HOU

期刊论文

expression pattern of mutations coordinated by target repression and promoter hypermethylation in acute myeloid

期刊论文

Ultraviolet-B induced expression of hypoxia-inducible factor 1α, transferrin receptor through EGFR/PI3K/AKT/DEC1 pathway

LI Yanhua, BI Zhigang

期刊论文

Effect of bradykinin on bradykinin-B2 receptor in rat aortic vascular smooth muscle cells and the involved

Wen YAN MD, Min FENG MD, Pei-Hua WANG MD, Dao-Wen WANG MD,

期刊论文

Synthesis and properties of water-soluble 1,9-dialkyl-substituted BF

Dan Wu, Gonzalo Durán-Sampedro, Donal F. O’Shea

期刊论文

Mutant DNA methylation regulators endow hematopoietic stem cells with the preleukemic stem cell property

null

期刊论文

Gene and protein expression of proteinase-activated receptor-1, 2 in a murine model of acute graft host

Quan LI MD , Weiming LI MD , Ping ZOU MD , Jian ZHANG BM ,

期刊论文

Effects of RNA interference targeting angiotensin 1a receptor on blood pressure and cardiac hypertrophy

ZHANG Jingqun, SUN Honglei, MA Yexin, WANG Daowen

期刊论文

Chimeric antigen receptor T cell targeting EGFRvIII for metastatic lung cancer therapy

Zhao Zhang, Jun Jiang, Xiaodong Wu, Mengyao Zhang, Dan Luo, Renyu Zhang, Shiyou Li, Youwen He, Huijie Bian, Zhinan Chen

期刊论文