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Residue substitution enhances the immunogenicity of neoepitopes from gastric cancers

Cancer Biology & Medicine 2021年第4期18卷 1053-1065页

作者： Huahui Yu Jieyu Li Yuan Yuan Yu Chen Jingwen Hong Chunmei ye Wansong Lin Huijing Chen Zengqing Guo Bo Li yunbin ye The School of Basic Medical Sciences Fujian Medical UniversityFuzhou 350122China Laboratory of Immuno-Oncology Fujian Cancer Hospital&Fujian Medical University Cancer HospitalFuzhou 350014China Fujian Key Laboratory of Translational Cancer Medicine Fuzhou 350014China BGI-Shenzhen Shenzhen 518083China BGI Education Center University of Chinese Academy of SciencesShenzhen 518083China Department of Oncology Fujian Cancer Hospital&Fujian Medical University Cancer HospitalFuzhou 350014China

Objective:Neoantigens arising from gene mutations in tumors can induce specific immune responses,and neoantigen-based immunotherapies have been tested in clinical ***,we characterized the efficacy of altered neoepitopes in improving immunogenicity against gastric ***:Raw data of whole-exome sequencing derived from a patient with gastric cancer were analyzed using bioinformatics methods to identify *** were modified by P1Y(the first amino acid was replaced by tyrosine)and P2L(the second amino acid was replaced by leucine).T2 binding and stability assays were used to detect the affinities between the neoepitopes and the HLA molecules,as well as the stabilities of *** cells(DCs)presented with neoepitopes stimulated naïve CD8+T cells to induce specific cytotoxic T *** and carboxyfluorescein succinimidyl ester were used to detect IFN-γand TNF-αlevels,and T cell *** was detected by flow *** cytotoxicity of T cells was determined using the lactate dehydrogenase ***:Bioinformatics analysis,T2 binding,and stability assays indicated that residue substitution increased the affinity between neoepitopes and HLA molecules,as well as the stabilities of *** presented with altered neoepitopes stimulated CD8+T cells to release more IFN-γand had a greater effect on promoting proliferation than wild-type ***8+T cells stimulated with altered neoepitopes killed more wild-type neoepitope-pulsed T2 cells than those stimulated with wild-type neoepitopes,by secreting more IFN-γ,TNF-α,and ***:Altered neoepitopes exhibited greater immunogenicity than wild-type *** substitution could be used as a new strategy for immunotherapy to target neoantigens.

关键词： Gastric cancer bioinformatics neoepitope residue substitution immunotherapy

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Randomized,multicenter,open-label trial of autologous cytokine-induced killer cell immunotherapy plus chemotherapy for squamous non-small-cell lung cancer:NCT01631357

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Signal Transduction and Targeted Therapy 2020年第1期5卷 418-420页

作者： Liang Liu Quanli Gao Jingting Jiang Junping Zhang Xin Song Jiuwei Cui yunbin ye Zhiyu Wang Xinwei Zhang Xiubao Ren Department of Immunology and Biotherapy Key Laboratory of Cancer Immunology and BiotherapyKey Laboratory of Cancer Prevention and TherapyTianjin’s Clinical Research Center for CancerTianjin Medical University Cancer Institute and HospitalTianjin 300060China Department of Immunotherapy Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer HospitalZhengzhou 450008 HenanChina Department of Tumor Biological Treatment Third Affiliated Hospital of Soochow UniversityChangzhou 213003 JiangsuChina Department of Oncology Shanxi Bethune HospitalTaiyuan 030032 ShanxiChina Cancer Biotherapy Center Third Affiliated Hospital of Kunming Medical University(Tumor Hospital of Yunnan Province)Kunming 650118 YunnanChina Cancer Center First Hospital of Jilin UniversityChangchun 130021 JilinChina Laboratory of Immuno-Oncology Fujian Cancer Hospital&Fujian Medical University Cancer HospitalFuzhou 350014 FujianChina Department of Immuno-Oncology Fourth Hospital of Hebei Medical UniversityShijiazhuang 050011 HebeiChina

Dear Editor,Cytokine-induced killer(CIK)cells have been recognized as a new type of anti-tumor effector *** cells are a mixture of T *** them,CD3+/CD56+T cells,which are rare in uncultured peripheral blood,are the main effector *** cells can proliferate rapidly in vitro,with stronger antitumor activity,broader target tumor spectrum,and lower adverse effect than other reported antitumor effector cells.1 Their ease of production in vitro and antitumor potential have made them suitable candidates for cell therapy regimens in solid and hematopoietic tumor treatments.1,2 Our previous retrospective study showed that the median progression-free survival(PFS)and overall survival(OS)in untreated,advanced non-small-cell lung cancer(NSCLC)patients who received CIK cell immunotherapy plus chemotherapy(13 and 24 months,respectively)were significantly longer than in those who received chemotherapy alone(6 and 10 months,respectively).2 But so far,there is no prospective,multicenter clinical study in lung *** on our previous study,we designed this randomized,multicenter,open-label trial to further evaluate the clinical efficacy of CIK cell immunotherapy plus chemotherapy in patients with advanced squamous NSCLC(*** number,NCT01631357).

关键词： killer chemotherapy squamous

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EGCG-NPs reduce the resistance of non-small cell lung cancer to EGFR-TKIs by inhibiting NF-κB signaling pathway

EGCG-NPs reduce the resistance of non-small cell lung cancer...

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2021年中国肿瘤标志物学术大会暨第十五届肿瘤标志物青年科学家论坛

作者： Lingyu zhang Dali Zheng yunbin ye Fujian Medical University Cancer Hospital Fujian Cancer Hospital Fujian Key Laboratory of Translational Cancer Medicine School and Hospital of Stomatology Fujian Medical University Fujian Cancer Hospital

Backgroud: The epidermal growth factor receptor(EGFR)-specific(TKIs) tyrosine kinase inhibitors have shown efficacy in the clinic, but tumors often become resistant to these therapies. Activation of the NF-κB promotes the resistance of Non-small cell lung cancer(NSCLC) to EGFR-TKIs. Herein, We investigated the ability of EGFR-TKIs combined with(-)-epigallocatechin-3-gallate Nanoparticles(EGCG-NPs) to inhibit cell proliferation, and NF-κB activation in several NSCLC resistant cell *** Design: NCI-PC9 cell line containing EGFR del 19 mutation was induced to establish the three generation EGFR-TKIs(Erlotinib, Afatinib and Osimertinib) resistant cell lines(PC9/ER,PC9/AR and PC9/OR) by low-concentration addition method in vitro. RNA sequencing(RNA-seq)was performed on PC9, PC9/ER, PC9/AR and PC9/OR to detect differentially expressed genes and involved pathways. The result of RNA-seq was verified by RT-PCR. And protein expression of P-NF-κB and P-EGFR was detected using Western blot. Experiments were conducted with EGCG-NPs and the EGFR-TKIs via MTT assay, colony formation assay, Western blot analysis and RT-PCR to detect the synergistic effects on ***: The established PC9/ER, PC9/AR and PC9/OR cells had over 180.051, 128.15 and 269.38-fold increased resistance to Erlotinib, Afatinib and Osimertinib than its sensitive parental PC9 cells,respectively. In terms of morphology, showed irregular cell characteristics. In terms of biological characteristics, resistant cells were characterized as slow proliferation, and prolonged multiplication time. RNA-seq revealed multiple changed pathways in R-PC9 cells compared to the parental cells and one of the most changed pathways was NF-κB signal pathway where most of gene activities were upexpression. The combination of EGFR-TKIs and EGCG-NPs resulted in greater inhibition of cell proliferation and colony formation than either agent alone. In addition, co-treatment with EGFR-TKIs and EGCG-NPs significantly inh

关键词： NSCLC EGFR-TKIs EGCG-NPs resisatance NF-κB

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Prognostic Values of Soluble PD-L1 in Nasopharyngeal Carcinoma

Prognostic Values of Soluble PD-L1 in Nasopharyngeal Carcino...

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2019年中国肿瘤标志物学术大会暨第十三届肿瘤标志物青年科学家论坛

作者： Chen,Yiping Lu,Tianzhu Guo,Qiaojuan ye,yunbin Pan,Jianji Fujian Medical University Cancer Hospital

Background/Objectives:The blockades of the immune checkpoint proteins play significant roles in tumor immunotherapies,particularly the inhibitors of the PD-1/*** aim of this study is to explore the expression difference of immune checkpoint proteins between NPC patients and healthy donors,and investigate the prognostic values of soluble form of programmed death-ligand1 (sPD-L1) in NPC.

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实体肿瘤TCR-T治疗研究的现状与面临的挑战

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中国肿瘤生物治疗杂志 2020年第9期27卷 959-967页

作者：叶春梅叶韵斌福建医科大学基础医学院福建医科大学附属肿瘤医院暨福建省肿瘤医院福建省肿瘤转化医学重点实验室福建福州350014

T细胞表面含有特异性的T细胞受体(T cell receptors,TCR),能够识别不同的肿瘤抗原,从而实现对癌变细胞的杀伤和清除。TCR工程化T细胞(TCR-engineered T cells,TCR-T)治疗即是通过钓取针对肿瘤细胞的特异性TCR,并应用基因工程技术改造T细... 详细信息

T细胞表面含有特异性的T细胞受体(T cell receptors,TCR),能够识别不同的肿瘤抗原,从而实现对癌变细胞的杀伤和清除。TCR工程化T细胞(TCR-engineered T cells,TCR-T)治疗即是通过钓取针对肿瘤细胞的特异性TCR,并应用基因工程技术改造T细胞,输注体内后可达到治疗肿瘤的目的。尽管TCR-T治疗取得一定成果,但是还存在治疗毒性、T细胞浸润有限、抗原特异性不佳等问题,需要不断优化TCR-T治疗的安全性和有效性。因此,本文阐述了目前国内外关于实体肿瘤TCR-T治疗的研究现状以及存在的问题与对策。

关键词：实体肿瘤过继性细胞免疫治疗 TCR工程化T细胞新抗原

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新媒体背景下写作课程教学改革探究

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科技创业月刊 2020年第11期33卷 150-152页

作者：叶云杉长春财经学院吉林长春130000

在新媒体发展中,内容逐渐丰富,人们在写作方面也展示出新的动能。互联网新媒体已经不单单是在传统写作的基础上开展,因此,写作教学也不能只依靠传统的教学模式进行。学生们需要在大学期间掌握更多的写作技能,利用新媒体的手段加强写作... 详细信息

在新媒体发展中,内容逐渐丰富,人们在写作方面也展示出新的动能。互联网新媒体已经不单单是在传统写作的基础上开展,因此,写作教学也不能只依靠传统的教学模式进行。学生们需要在大学期间掌握更多的写作技能,利用新媒体的手段加强写作。新媒介手段下,教师要利用更好适合现代学生发展的写作新模式,为社会培养写作人才。

关键词：新媒体写作教学人才培养

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Inhibitor of DNA binding 1(Id1) knockdown inhibits stemness and reverses EMT of colorectal cancer cells

Inhibitor of DNA binding 1(Id1) knockdown inhibits stemness ...

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第十四届全国肿瘤生物治疗大会

作者： Xiaolan Lai Jinrong Liao Lei Cao Mingang Ying Wansong Lin Chuanzhong Huang Jieyu Li Shuping Chen Chao Li Chunkang Yang Qiang Chen yunbin ye Graduate School of Education Fujian Medical University Department of Abdominal Surgery Fujian Provincial Cancer Hospital Department of Immuno-Oncology Laboratory Fujian Provincial Cancer Hospital Fujian Key Laboratory of Translational Cancer Medicine Department of Pathology Fujian Provincial Cancer Hospital Fuzhou Department of Medical Oncology Union Hospital of Fujian Medical University

Background: Inhibitor of DNA binding 1(Id1) is essential for the maintenance of self-renewal of neural and embryonic stem cells;however, its roles in human colorectal stem-like cells(CSCs) and epithelialmesenchymal transition(EMT) are still elusive. Materials and Methods: The messenger RNA(mR NA) and protein levels of Id1 and CD133 were detected by reverse transcription quantity PCR, immunohistochemistry analysis in normal mucosa and primary colorectal cancer(CRC) specimens. Id1 was stably knockdown(KD) in human colon cancer cell lines by RNA interference method. Spheres forming assay and tumorigenic assay were performed to evaluate self-renewal capacity in vitro and tumor initiate in vivo, respectively. CSC and EMT relative makers and TCF/LEF promoter activity were assessed after Id1 KD in HCT116 cells. Results: Id1 protein expression was significantly related with CRC differentiation status, however, CD133 expression was positively related with T categories in 75 CRC patients. Spearman correlation revealed that Id1 expression was significantly and positively correlated with CD133 expression in both mR NA(r=0.401, P=0.031) and protein levels(r=0.309, P=0.005). Id1 KD of HCT116 caused decreased sphere-formation capacity compared to the controls. Likewise,CD133 and several other stem cell makers expression in the Id1 KD cells were remarkably reduced compared to the control cells. The Id1 KD cells also demonstrated up-regulated E-cadherin and down-regulated snail and twist expression, which are the typical phenotype of EMT. And also, the down-regulation of nucleus and cytoplasm β-catenin and the TCF/LEF promoter activity was detected in Id1 KD cells compared that in controls. In vivo test confirmed that down-regulation of Id1 led to decrease tumor-initiating ability and suppress tumor growth in nude mice. Conclusion: Our findings indicate that down-regulation of Id1 can suppress the self-renewal and reverse EMT features of CRC, possibly through Wnt pathway. Id1 could

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乳化沥青水泥混凝土力学性能研究

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交通科技 2016年第1期26卷 131-133页

作者：赵振岐叶云斌同济大学道路与交通工程教育部重点实验室上海200092 宁波市交通工程质量安全监督站宁波315000

为了解乳化沥青水泥混凝土的力学性能,通过室内试验,探究乳化沥青掺量对水泥混凝土抗压、弯拉强度的影响,在此基础上研究乳化沥青水泥混凝土的刚度和疲劳特性。试验结果表明,在不改变弯拉强度的情况下,乳化沥青的加入能够降低水泥混凝... 详细信息

为了解乳化沥青水泥混凝土的力学性能,通过室内试验,探究乳化沥青掺量对水泥混凝土抗压、弯拉强度的影响,在此基础上研究乳化沥青水泥混凝土的刚度和疲劳特性。试验结果表明,在不改变弯拉强度的情况下,乳化沥青的加入能够降低水泥混凝土的刚度,增加其疲劳寿命次数,改善水泥混凝土的性能。

关键词：乳化沥青水泥混凝土力学强度刚度疲劳性能

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隧道爆破施工对近接既有隧道的影响分析

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交通科技 2015年第3期25卷 129-132页

作者：叶云斌方继伟宁波市交通工程质量安全监督站宁波315040 宁波市交通建设工程试验检测中心有限公司宁波315113

新建隧道爆破施工对既有隧道影响严重,为了对影响规律进行分析,对既有隧道进行爆破振动监测。通过对监测爆破振动数据进行统计分析,得出爆破振动振速传播规律,归纳分析得到爆破振动传播规律的萨氏公式,并得到振动速度与爆心距和最大段... 详细信息

新建隧道爆破施工对既有隧道影响严重,为了对影响规律进行分析,对既有隧道进行爆破振动监测。通过对监测爆破振动数据进行统计分析,得出爆破振动振速传播规律,归纳分析得到爆破振动传播规律的萨氏公式,并得到振动速度与爆心距和最大段装药量的关系,为有效地减小爆破振速提供理论依据。

关键词：爆破振动振动速度爆心距最大段装药量

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慢病毒介导的CARMA1稳定沉默抑制K562细胞的侵袭和转移能力

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细胞与分子免疫学杂志 2014年第7期30卷 691-695页

作者：刘枋王凌燕李洁羽陈淑萍叶韵斌福建医科大学教学医院福建省肿瘤医院肿瘤免疫学研究室福建省肿瘤转化医学重点实验室福建福州350014

目的研究RNAi技术稳定沉默caspase募集结构域膜相关鸟苷酸激酶蛋白1(CARMA1)基因后对K562细胞增殖、克隆形成和侵袭转移的影响。方法应用慢病毒介导的RNAi技术构建稳定沉默CARMA1基因的K562细胞,反转录PCR和Western blot法分别检测CARMA... 详细信息

目的研究RNAi技术稳定沉默caspase募集结构域膜相关鸟苷酸激酶蛋白1(CARMA1)基因后对K562细胞增殖、克隆形成和侵袭转移的影响。方法应用慢病毒介导的RNAi技术构建稳定沉默CARMA1基因的K562细胞,反转录PCR和Western blot法分别检测CARMA1 mRNA和蛋白的抑制情况。应用台盼蓝拒染法分析细胞增殖情况,克隆形成实验观察细胞克隆形成,TranswellTM实验(含Matrigel或不含Matrigel)检测体外迁移与侵袭能力的改变。反转录PCR和Western blot技术分析相关信号通路分子的改变,并探讨可能机制。结果成功构建6株细胞株:其中1株为阴性对照(K562/sh-eGFP),另5株为CARMA1基因沉默的细胞株。K562/shCARMA 1-93对CARMA1的抑制效果最好,利用该模型进行后续研究。台盼蓝拒染法和克隆形成实验表明,K562/shCARMA 1-93的生长和克隆形成能力受到明显抑制(P<0.01)。与空白对照K562和阴性对照K562/sh-eGFP相比,细胞生长抑制率分别为29.3%和28.6%;克隆形成抑制率分别为37.6%和34.1%。体外迁移和侵袭转移实验证实,与对照组相比,K562/shCARMA1-93穿膜细胞数明显减少,有统计学差异(P<0.01)。CARMA1受抑制后,信号通路分子核转录因子-κB(NF-κB)及早期生长反应基因1(EGR1)的表达也随之下降。结论 CARMA1的稳定沉默会抑制K562细胞的增殖、克隆形成和侵袭转移,这可能与NF-κB、JNK/EGR-1信号通路受抑制有关。

关键词： caspase募集结构域膜相关鸟苷酸激酶蛋白1(CARMA1) 慢性粒细胞性白血病慢病毒迁移侵袭

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