靶向血管内皮细胞治疗肝癌的实验研究

目的 运用抗肝癌区血管内皮细胞的单克隆抗体进行抑癌实验。方法 通过建立裸小鼠人肝癌动物模型来进行,抑瘤实验。结果 抗肝癌区血管内皮细胞的单克隆抗体在肝癌动物模型的抑瘤裕有明显的抑瘤作用。结论 抗体在动物实验中明显的抑瘤作用,表明通过应用这种抗体可对肝癌进行以血管为靶向的生物治疗,从而为肝癌的治疗提供一种新的治疗方法。     

Polymeric multilayer capsules delivering biotherapeutics

Polymeric multilayer capsules have emerged as a novel drug delivery platform. These capsules are fabricated through layer-by-layer sequential deposition of polymers onto a sacrificial core template followed by the decomposition of this core yielding hollow capsules. The resulting nanometer thin membrane is permselective, allowing diffusion of water and ions but excluding larger molecules. Moreover, the sequential fabrication procedure allows a precise fine-tuning of the capsules’ physicochemical and biological properties. These properties have put polymeric multilayer capsules under major attention in the field of drug delivery. In this review we focus on polymeric multilayer capsule mediated delivery of biotechnological macromolecular drugs such as peptides, proteins and nucleic acids.     

Chloride channel-mediated brain glioma targeting of chlorotoxin-modified doxorubicine-loaded liposomes

The chlorotoxin (ClTx), a scorpion-derived peptide, binding to gliomas with high specificity, was firstly applied to establish the ClTx-modified doxorubicin (DOX)-loaded liposome delivery system for targeting the brain glioma and improving the anticancer efficacy. In vitro physicochemical characterization of the novel liposome system presented satisfactory size of 100 nm with uniform distribution, high encapsulation efficiency and adequate loading capacity of both fluorescent probe and anticancer drug. It was demonstrated quantitatively by the spectrophotofluorometry and flow cytometry and qualitatively by the confocal microscopy that ClTx highly facilitated the uptake of liposomes by three glioma cell lines and one endothelial cell line. In vitro cytotoxicity studies proved that the presence of ClTx increased the cytotoxicity against glioma cells and endothelial cells with various levels for different cell lines. In BALB/c mice bearing U87 tumor xenografts, biodistribution of DiR-loaded liposomes by body imaging and anti-glioma pharmacodynamics of DOX-loaded liposomes were investigated. The ClTx-modified liposomes showed more accumulation in the subcutaneous and intracranial tumors, higher tumor growth inhibition and lower blood toxicity in the armpit tumor model. The in vitro and in vivo results exhibited good correlation of glioma targeting of the ClTx-modified liposomes. Significantly, with the ClTx as the targeting ligand, the liposomes might serve as an applicable delivery system for brain glioma therapy or imaging.     

PEG-PLGA纳米颗粒载体药物靶向治疗肿瘤的研究进展

肿瘤是近年来临床多发的难治性疾病,是导致死亡的主要原因之一,手术及放、化疗是常规治疗手段.但晚期转移者无法手术,传统放、化疗缺乏针对性,且多有严重不良反应,致使人们普遍关注靶向治疗,因此,其已成为一个热点问题.本文纳入大量相关中外文献,综述并讨论近年来以PEG-PLGA纳米粒子为载体治疗肿瘤的靶向给药系统的研究进展,并分析了存在的问题.     

老年晚期非小细胞肺癌的靶向治疗

老年肺癌发病及死亡呈上升趋势,但老年患者整体接受积极治疗的人数却明显少于非老年患者。随着分子靶向治疗药物,如人表皮生长因子受体酪氨酸激酶抑制剂、新生血管抑制剂、抗肿瘤单克隆抗体及多靶点药物的出现,老年晚期非小细胞肺癌患者的总生存时间得到显著延长,生活质量得到明显改善。靶向治疗已成为最有希望且能显著改善老年患者预后的治疗方法。     

直肠癌同步放化疗与辅助化疗

辅助及新辅助治疗是直肠癌最重要的综合治疗手段,新辅助同步放化疗和术后辅助化疗在直肠癌治疗中起着至关重要的作用。一些新的化疗和靶向药物的出现可以进一步改善直肠癌的治疗效果。     

肝癌基因治疗的基础研究与临床应用

肝癌基因治疗发展至今已有30余年,基因治疗的策略、载体和治疗基因随着科学的发展不断更新。近年来由于基础研究的重要突破,肝癌基因治疗逐步由基础研究走向临床治疗,并在临床实践过程中不断积累经验,不断成熟。本文将结合自身工作就肝癌基因治疗的基础研究与临床应用作一简短综述。     

Engineering filamentous phage carriers to improve focusing of antibody responses against peptides

The filamentous bacteriophage are highly immunogenic particles that can be used as carrier proteins for peptides and presumably other haptens and antigens. Our previous work demonstrated that the antibody response was better focused against a synthetic peptide if it was conjugated to phage as compared to the classical carrier, ovalbumin. We speculated that this was due, in part, to the relatively low surface complexity of the phage. Here, we further investigate the phage as an immunogenic carrier, and the effect reducing its surface complexity has on the antibody response against peptides that are either displayed as recombinant fusions to the phage coat or are chemically conjugated to it. Immunodominant regions of the minor coat protein, pIII, were removed from the phage surface by excising its N1 and N2 domains (Δ3 phage variant), whereas immunodominant epitopes of the major coat protein, pVIII, were altered by reducing the charge of its surface-exposed N-terminal residues (Δ8 phage variant). Immunization of mice revealed that the Δ3 variant was less immunogenic than wild-type (WT) phage, whereas the Δ8 variant was more immunogenic. The immunogenicity of two different peptides was tested in the context of the WT and Δ3 phage in two different forms: (i) as recombinant peptides fused to pVIII, and (ii) as synthetic peptides conjugated to the phage surface. One peptide (MD10) in its recombinant form produced a stronger anti-peptide antibody response fused to the WT carrier compared to the Δ3 phage carrier, and did not elicit a detectable anti-peptide response in its synthetic form conjugated to either phage carrier. This trend was reversed for a different peptide (4E10_L), which did not produce a detectable anti-peptide antibody response as a recombinant fusion; yet, as a chemical conjugate to Δ3 phage, but not WT phage, it elicited a highly focused anti-peptide antibody response that exceeded the anti-carrier response by ∼65-fold. The results suggest that focusing of the antibody response against synthetic peptides can be improved by decreasing the antigenic complexity of the phage surface.