胃癌血管靶向肽与endostatin重组蛋白的抗肿瘤血管治疗疗效及机制研究

批准号:
81972895
项目类别:
面上项目
资助金额:
51.0 万元
负责人:
陈蓓
依托单位:
学科分类:
肿瘤综合治疗
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
陈蓓
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中文摘要
肿瘤抗血管治疗具有划时代意义,然而胃癌抗血管药物靶向性欠佳,影响疗效且增加副作用。提高胃癌抗血管治疗的靶向性意义重大。我们在前期研究中通过噬菌体肽库筛选获得了一段胃癌血管的靶向性短肽,体外荧光及体内核素显像证实该短肽可靶向性结合于胃癌血管。进而在预实验中通过基因重组将该短肽与抗血管药物内皮抑素(endostatin)融合,结果显示融合蛋白可选择性富集于胃癌组织。据此我们提出科学假设:利用胃癌血管靶向肽可介导内皮抑素靶向性分布于胃癌组织,从而提高胃癌抗血管治疗药物的疗效、降低副作用。因此,本课题拟首先纯化鉴定该重组蛋白,通过一系列核素显像、分子生物等试验验证其靶向性分布、抗肿瘤效应及副作用,并通过检测VEGF及bFGF信号通路探讨其机制。本课题的完成将为提高胃癌抗血管药物的靶向性提供新方法,为改善胃癌抗血管治疗的疗效提供依据。
英文摘要
Tumor vascular targeted therapy is a milestone in the battle against cancer. However, the lack of tumor specificity has affected the clinical use of anti-vascular agents. Therefore, it is of great importance to improve the specificity of anti-vascular therapy. Previously, using the phage displayed peptide library, we acquired a gastric cancer vascular targeted peptide. In vitro and in vivo immunofluorescence test and radionuclide imaging showed that the peptide could selectively accumulate in gastric cancer vasculature. In our preliminary experiment, using gene recombination method, we constructed a novel fusion protein of the targeted peptide and endostatin which was an effective anti-vascular agent. It was shown that the fusion protein could selectively accumulate in gastric cancer. Accordingly, we assumed that the targeted peptide could act as a selective vector and induce targeted distribution of endostatin in gastric cancer, so as to improve the therapeutic effect and reduce the side effects. Herein, we plan to purify the recombinant protein first, and elucidate the selective distribution, the anti-vascular effect and the side effects of the fusion protein through radionuclide imaging and other molecular biologic tests. We will also detect the VEGF and bFGF signaling pathway to investigate the possible mechanisms. Our results might find a new way to improve the specificity and therapeutic effects of anti-vascular agents for gastric cancer.
期刊论文列表
专著列表
科研奖励列表
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专利列表
DOI:10.3892/ol.2023.13718
发表时间:2023-03
期刊:Oncology letters
影响因子:2.9
作者:Li J;Li B;Xu J;Wang H;Gao Q;Ye F;Xu Y;Wu S;Cheng S;Lu Y;Guan J;Chen B
通讯作者:Chen B
DOI:10.1186/s13018-023-04166-w
发表时间:2023-10-27
期刊:JOURNAL OF ORTHOPAEDIC SURGERY AND RESEARCH
影响因子:2.6
作者:Chen, Bei;Luo, Yeqiang;Zhang, Zhongxiu;Lin, Shanghui;Wang, Renkai;Li, Baofeng
通讯作者:Li, Baofeng
DOI:10.3389/fsurg.2022.926825
发表时间:2022
期刊:FRONTIERS IN SURGERY
影响因子:1.8
作者:Luo, Yeqiang;Lin, Shanghui;Kong, Lingchuang;Jin, Yan;Wang, Renkai;Zhang, Ying;Li, Baofeng;Chen, Bei
通讯作者:Chen, Bei
DOI:10.1080/21681163.2023.2261554
发表时间:2023-09
期刊:Computer Methods in Biomechanics and Biomedical Engineering: Imaging & Visualization
影响因子:--
作者:Yeqiang Luo;Jing Liang;Shanghui Lin;Tian Bai;Lingchuang Kong;Yan Jin;Xin Zhang;Baofeng Li;Bei Chen
通讯作者:Yeqiang Luo;Jing Liang;Shanghui Lin;Tian Bai;Lingchuang Kong;Yan Jin;Xin Zhang;Baofeng Li;Bei Chen
DOI:10.3389/fendo.2021.627718
发表时间:2021
期刊:Frontiers in endocrinology
影响因子:5.2
作者:Li B;Wang R;Huang X;Ou Y;Jia Z;Lin S;Zhang Y;Xia H;Chen B
通讯作者:Chen B
国内基金
海外基金
