免疫毒素的抗肿瘤研究

免疫毒素是由具有导向能力的载体（抗体或细胞因子）和具有细胞毒性的分子（毒素）偶联而成的具有特异性细胞杀伤能力的杂合分子,是一种靶向药物。免疫毒素首先利用肿瘤细胞上导向分子的受体与细胞结合,然后进入细胞,再由毒素发挥蛋白质合成抑制作用,最终导致靶细胞死亡。与其他抗肿瘤药物相比,免疫毒素具有毒性强和特异性高的优点,在肿瘤治疗中显示出巨大的应用前景。简要概述了免疫毒素的作用机理、制备及其抗肿瘤研究进展。     

抗肿瘤免疫毒素稳定性的研究进展

免疫毒素 (immunotoxins)是由某些细菌和植物产生的毒素蛋白与抗体或生长因子等靶向分子连接而成 ,用于杀伤表面带有特定抗原或受体的细胞。在试验中 ,免疫毒素在肿瘤周围环境中的稳定性是影响其抗肿瘤效果的主要因素之一。本文主要对几种由不同形式的抗体Fv段构建的免疫毒素的稳定性进行了比较 ,并对定点突变和PEG化学修饰提高免疫毒素稳定性的方法做一简要介绍。     

Immunotoxins

Immunotoxins (ITs) are chimeric molecules constructed by covalently conjugating monoclonal antibodies (MoAbs) to plant or bacterial toxins (e.g. ricin or pseudomonas exotoxin). The antibody moiety allows specific targeting of ITs to tumor-associated antigens, while the toxin moiety is responsible for cell killing by irreversible inactivation of protein synthesis. Since ITs must reach the cytosol to kill cells, the rates of endocytosis, the pathways of intracellular routing, and the rates of translocation to the cytoplasm are important determinants of the efficacy of an IT. Promisingin vitro andin vivo IT results have been reported by many groups, and phase I clinical trials in cancer patients are currently underway.This research was supported in part by a First Independent Research and Training award from the National Institutes of Health (R29 CA 46134-03).     

Immunotoxins

Many types of tumour cell express high levels of surface antigens which are largely absent from normal cells. Monoclonal antibodies against these surface antigens can be coupled to potent toxins to form conjugates (immunotoxins) which selectively kill the antigen-bearing cells. This article describes the components of immunotoxins, their modes of action and their clinical applications.     

Immunotoxins

Immunotoxins are hybrid molecules formed by coupling antibody molecules to powerful toxins of plant or bacterial origin. In experimental systems, immunotoxins have been found to kill cancer cells with great potency and specificity. This article reviews the current status of immunotoxins and some of the problems that have to be overcome before they can be used to treat human malignant disease.     

Radiation Therapy for Skin Cancer

Local control, cosmesis and functional results were evaluated in 315 cases of skin cancer in 247 patients treated with radiation therapy. The initial recurrence rate for basal cell carcinoma was 7.8 percent and for squamous cell carcinoma was 14.9 percent. Ultimate local control was achieved in 98.7 percent of the cases of basal cell carcinoma and in 94.0 percent of the cases of squamous cell carcinoma with use of further irradiation or other therapeutic modalities. Ultimate local control rates were comparable to other therapeutic modalities. Cosmetic and functional results were excellent. Cartilage necrosis was not a significant problem. Radiation therapy may offer advantages in certain clinical situations and should be considered as a mode of therapy in the treatment of skin cancer.     

Multifunctional Nanoparticles for Prostate Cancer Therapy

The relapse of cancer after first line therapy with anticancer agents is a common occurrence. This recurrence is believed to be due to the presence of a subpopulation of cells called cancer stem cells in the tumor. Therefore, a combination therapy which is susceptible to both types of cells is desirable. Delivery of this combinatorial approach in a nanoparticulate system will provide even a better therapeutic outcome in tumor targeting. The objective of this study was to develop and characterize nanoparticulate system containing two anticancer agents (cyclopamine and paclitaxel) having different susceptibilities toward cancer cells. Both drugs were entrapped in glyceryl monooleate (GMO)-chitosan solid lipid as well as poly(glycolic-lactic) acid (PLGA) nanoparticles. The cytotoxicity studies were performed on DU145, DU145 TXR, and Wi26 A4 cells. The particle size of drug-loaded GMO-chitosan nanoparticles was 278.4 ± 16.4 nm with a positive zeta potential. However, the PLGA particles were 234.5 ± 6.8 nm in size with a negative zeta potential. Thermal analyses of both nanoparticles revealed that the drugs were present in noncrystalline state in the matrix. A sustained in vitro release was observed for both the drugs in these nanoparticles. PLGA blank particles showed no cytotoxicity in all the cell lines tested, whereas GMO-chitosan blank particles showed substantial cytotoxicity. The types of polymer used for the preparation of nanoparticles played a major role and affected the in vitro release, cytotoxicity, and uptake of nanoparticles in the all the cell lines tested.KEY WORDS: cancer stem cells, cyclopamine, glyceryl monooleate, nanoparticles, PLGA     

利用PE构建免疫毒素

利用ＰＥ构建免疫毒素蒋欣黄华梁（中国科学院遗传研究所,北京１００１０１）ＰＥａｎｄＰＥ－ｄｅｒｉｖｅｄＲｅｃｏｍｂｉｎａｎｔＩｍｍｕｎｏｔｏｘｉｎｓＪｉａｎｇＸｉｎＨｕａｎｇＨｕａｌｉａｎｇ（ＩｎｓｔｉｔｕｔｅｏｆＧｅｎｅｔｉｃｓ,ＣｈｉｎｅｓｅＡｃ...     

肿瘤靶向治疗在NSCLC中的应用

肺癌已成为21世纪威胁人类健康最主要原因之一,全球每年因非小细胞肺癌(NSCLC)死亡的人数超过100万人.传统的抗肿瘤药物极大改善了NSCLC患者的预后.由于缺乏选择性和很强的细胞毒性,多中心研究表明化疗方案疗效已经达到治疗平台,应致力于研发作用机制不同于化疗的药物.肿瘤靶向治疗通过针对特异性的靶点来杀死和抑制肿瘤细胞,避免了对正常细胞的伤害,已成为当前肿瘤研究的热点,并已在临床肿瘤治疗中取得了一定疗效.随着肿瘤分子生物学与细胞生物学的发展,人们对肺癌癌变、侵袭转移的分子机理以及生物信号传导通路的认识加深,新的靶向治疗药物不断出现.本文就近年靶向治疗技术的进展及分子靶向药物在NSCLC中的应用作一综述.     

光动力技术治疗胃癌的进展及展望

近年来应用光动力技术治疗胃癌取得了可喜的进步,它对各个时期的胃癌均有比较满意的临床效果。本文通过对国内外近年来用光动力技术治疗胃癌方面的文献进行综述,系统阐述光动力运用于胃癌治疗这一项技术的原理、机制,光敏剂、光源及临床效果等方面,并总结了这项技术在治疗胃癌方面的优点和相关问题。     

RAS相关通路介导的结直肠癌药物联合治疗的应用

RAS相关信号通路在结直肠癌的发生、发展中起着重要作用，与该类肿瘤细胞的增殖、转移、凋亡密切相关。目前，包括靶向药物、化疗药物的单药治疗对结直肠癌的临床获益并不理想。近年来，在临床试验和临床前研究中RAS相关信号通路的抑制剂与其他药物的联合应用取得了良好效果，其中EGFR抑制剂、VEGF抑制剂、RAS直接抑制剂、MEK抑制剂和RAF抑制剂的表现尤为突出。本文就RAS相关信号通路与结直肠癌的作用关系、临床试验和临床前研究中的联合用药策略以及组合用药的耐药机制研究进行系统性综述，以期为未来临床多药治疗策略奠定基础。