Research progress of nanocarriers for gene therapy targeting abnormal glucose and lipid metabolism in tumors

In recent years, the incidence of various types of tumors has gradually increased, and it has also been found that there is a certain correlation between abnormal glucose and lipid metabolism and tumors. Glycolipid metabolism can promote tumor progression through multiple pathways, and the expression of related genes also directly or indirectly affects tumor metabolism, metastasis, invasion, and apoptosis. There has been much research on targeted drug delivery systems designed for abnormal glucose and lipid metabolism due to their accuracy and efficiency when used for tumor therapy. In addition, gene mutations have become an important factor in tumorigenesis. For this reason, gene therapy consisting of drugs designed for certain specifically expressed genes have been transfected into target cells to express or silence the corresponding proteins. Targeted gene drug vectors that achieve their corresponding therapeutic purposes are also rapidly developing. The genes related to glucose and lipid metabolism are considered as the target, and a corresponding gene drug carrier is constructed to influence and interfere with the expression of related genes, so as to block the tumorigenesis process and inhibit tumor growth. Designing drugs that target genes related to glucose and lipid metabolism within tumors is considered to be a promising strategy for the treatment of tumor diseases. This article summarizes the chemical drugs/gene drug delivery systems and the corresponding methods used in recent years for the treatment of abnormal glucose and lipid metabolism of tumors, and provides a theoretical basis for the development of glucolipid metabolism related therapeutic methods.     

Transforming targeted cancer therapy with PROTACs: A forward-looking perspective

Small-molecule targeted protein degraders have in recent years made a great impact on the strategies of many industry and academic cancer research endeavours. We seek here to provide a concise perspective on the opportunities and challenges that lie ahead for bifunctional degrader molecules, so-called ‘Proteolysis Targeting Chimeras (PROTACs),’ in the context of cancer therapy. We highlight high-profile studies that support the potential for PROTAC approaches to broaden drug target scope, address drug resistance, enhance target selectivity and provide tissue specificity, but also assess where the modality is yet to fully deliver in these contexts. Future opportunities presented by the unique bifunctional nature of these molecules are also discussed.     

重症监护室医院感染目标性监测综合干预效果评价的Meta分析

目的 分析目标性监测综合干预在我国ICU医院感染防控中的效果.方法 文献检索中国知网、维普和万方数据库,将基于ICU医院感染目标性监测综合干预的前后对照研究纳入,并应用R 3.0.3软件进行Meta分析.结果 共纳入11篇文献.综合干预前后,各项感染率的合并相对危险度(RR)分别为:感染率0.70(95 ％CI:0.56～0.87),例次感染率0.70(95％ CI:0.58～0.84),千日感染率0.76(95％CI:0.60～0.95),千日例次感染率0.66(95％CI:0.54～0.80),干预前后差异均有统计学意义(P均＜0.05).干预前后各项器械使用率合并RR分别为:中心静脉插管0.96 (95％CI:0.82～1.12),呼吸机1.06(95％CI:0.97～1.15),导尿管0.93(95％CI:0.86～1.00),差异均无统计学意义(P均＞0.05);中心静脉插管、呼吸机相关感染率干预后合并RR分别为:0.75 (95％CI:0.53～0.88)、0.63(95％CI:0.56～0.72),差异均有统计学意义(P均＜0.05),但导尿管相关感染干预后仅有下降趋势0.85 (95％CI:0.68～1.06),差异并无统计学意义(P均＞0.05).结论 基于目标性监测的综合干预措施对医院感染防控效果显著,并且具有进一步挖掘空间,值得进一步临床推广应用.     

贝伐珠单抗联合化疗治疗晚期宫颈癌患者的针对性护理效果观察

目的 观察针对性护理在贝伐珠单抗联合化疗治疗晚期宫颈癌中的应用效果.方法 选取2014年1月-2018年12月中国人民解放军联勤保障部队第九○一医院肿瘤二科收治的晚期宫颈癌患者72例,按照随机数字表法分为观察组和对照组各36例.2组患者均给予贝伐珠单抗联合化疗治疗,观察组给予针对性护理,对照组给予常规护理.比较2组患者...     

Receptor-mediated targeted drug delivery systems for treatment of inflammatory bowel disease: Opportunities and emerging strategies

Inflammatory bowel disease (IBD) is a chronic intestinal disease with painful clinical manifestations and high risks of cancerization. With no curative therapy for IBD at present, the development of effective therapeutics is highly advocated. Drug delivery systems have been extensively studied to transmit therapeutics to inflamed colon sites through the enhanced permeability and retention (EPR) effect caused by the inflammation. However, the drug still could not achieve effective concentration value that merely utilized on EPR effect and display better therapeutic efficacy in the inflamed region because of nontargeted drug release. Substantial researches have shown that some specific receptors and cell adhesion molecules highly expresses on the surface of colonic endothelial and/or immune cells when IBD occurs, ligand-modified drug delivery systems targeting such receptors and cell adhesion molecules can specifically deliver drug into inflamed sites and obtain great curative effects. This review introduces the overexpressed receptors and cell adhesion molecules in inflamed colon sites and retrospects the drug delivery systems functionalized by related ligands. Finally, challenges and future directions in this field are presented to advance the development of the receptor-mediated targeted drug delivery systems for the therapy of IBD.     

表皮生长因子受体及其靶向治疗

表皮生长因子受体(epidermalgrowth factor receptor,EGFR)是与大多数上皮实体肿瘤密切相关的一种跨膜糖蛋白.EGFR的致癌机制很多,并且往往呈现出肿瘤特异性.由于EGFR在许多肿瘤发生过程中起着重要的促进作用,因此,EGFR已成为肿瘤靶向治疗领域的一个研究热点.目前,靶向EGFR的药物主要有两种:EGFR胞外区结合抗体和小分子酪氨酸激酶抑制剂.此文对EGFR的结构、致癌机制、靶向治疗等进行探讨,希望通过在分子和基因水平对EGFR在恶性肿瘤中所起作用的了解,促进肿瘤特异性抗癌药物的设计、开发和临床评价.     

抗体偶联药物研究进展

抗体-药物偶联物(Antibody-drug conjugates,ADCs)由“弹头”药物(细胞毒药物)、抗体以及偶联抗体和药物的偶联链3部分组成,其作为一种新型药物,结合了抗体的靶向特异性和小分子药物的细胞毒作用,已成为当今肿瘤研究领域的热点。根据其细胞毒药物来源可分为陆地与海洋两大类,本文总结了近年来这两大类抗体偶联药物的研究进展,并从靶点的特异性、抗体的亲和力、高效的细胞毒分子及合适的偶联链等方面对ADCs的发展关键进行了简要评述。     

表皮生长因子受体在胰腺癌治疗中的进展

胰腺癌是一种比较常见的消化道恶性肿瘤,传统的化疗和放疗效果均不甚理想。表皮生长因子受体(EGFR)信号转导通路在胰腺癌细胞的发生、增殖、转移、血管形成等方面有重要作用,针对EGFR信号通路的靶向治疗药物已陆续开发和应用。本文就EGFR的结构、功能以及EGFR抑制剂在胰腺癌治疗中的作用予以简要综述。     

肿瘤相关巨噬细胞在肿瘤发病过程及治疗中的研究进展

巨噬细胞是机体内参与免疫反应的重要免疫细胞之一, 随着人们对巨噬细胞研究的深入, 肿瘤相关巨噬细胞(TAMs)这一概念被提出。TAMs是肿瘤微环境(TME)中复杂而异质的细胞群, 与肿瘤相关炎症的发生有密切关系, 可影响肿瘤的生长、侵袭、转移和肿瘤内血管形成, 也可分泌多种细胞因子和趋化因子抑制抗肿瘤免疫反应的发生。由此可见, TAMs与肿瘤的发生发展有密切的关系, 因此成为肿瘤治疗的有趣靶点。本文就TAMs如何参与肿瘤进展、如何在临床中用于肿瘤治疗的靶点进行综述。     

胃癌靶点Claudin 18.2的研究进展

我国胃癌的早期诊断率低,大多数病人就诊时已为晚期,失去了根治性手术的机会。晚期胃癌目前以化疗药物治疗为主,但化疗药物具有选择性低、毒副作用大等缺点。随着分子生物学的进展,靶向药物对胃癌的治疗展现出了良好的前景,成为晚期胃癌治疗新的选择。目前,对胃癌有成效的靶向治疗以抗人表皮生长因子受体-2(HER-2)药物为主,抗血管内皮生长因子药物及免疫检查点抑制剂对胃癌的治疗也取得了一定的成效。近年来,Claudin18.2靶点成为最具前景的胃癌治疗性靶点。该研究针对Claudin18.2的研究进展展开综述。