宿主导向疗法在结核病中的作用

结核病是单一病原体感染中致死率最高的传染性疾病之一,其致病菌结核分枝杆菌在感染过程中诱发的过度炎症反应是造成患者组织损伤、器官衰竭的关键因素。如何改善这一病理反应对于结核病的治疗具有积极作用。宿主导向疗法(host-directed therapy,HDT)是近几年提出的一种新型抗结核辅助治疗策略。与传统抗生素相比,抗结核的HDT治疗策略从直接杀伤结核分枝杆菌转向了调节宿主的免疫反应,一方面减轻细菌感染诱发的过度炎症反应以及病理损伤,另一方面通过增强宿主本身的免疫力来控制感染的细菌。本文对宿主导向疗法在抗结核方面的研究进展进行了系统性的总结,以期为抗结核辅助疗法的开发提供一定的理论基础和思路。     

IgY抗体作为导向载体对消化系统肿瘤的选择性识别作用研究

用生物治疗方法治疗肿瘤已被视为肿瘤治疗的第四大疗法,其主要是免疫治疗．包括抗体与偶合物,肿瘤疫苗等。而要想获得有效的肿瘤治疗药物．其关键是要寻找小型化的、高效的导向载体。我们的实验室以低分化腺胃癌的P110癌蛋白作为抗原,免疫SPF鸡,从卵黄中提取抗体IgY作为植物毒素的导向性载体;实验结果证明,IgY能特异性地选择识别消化系统的肿瘤组织,为进一步研究肿瘤的导向药物提供了另一理论依据。     

选择性支气管动脉插管转铁蛋白受体单克隆抗体灌注治疗中晚期肺癌(附68例临床报告)

本文对68例中晚期肺癌进行选择性支气管动脉插管采用转铁蛋白受体单克隆抗体与表阿霉素、顺伯等药物制成偶联物灌注。结果显示,肿瘤明显消退24例(35.2％),部分消退36例(52.5％),无变化8例(12.3％),总有效率为87.7％。通过对支气管动脉插管,导向灌注疗法结果显示,本疗法优于周围静脉供药,且无严重并发症,副作用轻,不失为一种可供选择的治疗方法。     

彩超导向置管引流在胆道急症中的应用

目的探讨彩超导向置管引流在胆道急症中应用的临床疗效。方法对我院收治的103例胆道急症患者使用彩超导向置管引流的方法进行治疗,探讨彩超导向置管引流在对于胆道急症患者的治疗效果。结果通过使用彩超导向置管引流的治疗后,所有的胆道急症患者均得到了较好的治疗。结论彩超导向置管引流在对于胆道急症患者实施治疗的过程中能够取得较好的治疗效果,在临床对于胆道急症患者实施治疗的过程中可以进行推广和使用。     

导向性纤溶酶原激活剂的研究

溶栓疗法是血栓治疗中的一种重要措施.研制具有高选择性的导向性纤溶酶原激活剂有着重大的理论意义和实用价值.采用血栓特异的单克隆抗体及其片段来介导溶栓剂已展示出较好的应用前景.双功能抗体以及同时具有抗栓,抗凝活性的小肽正逐渐拓宽人们有关导向分子研制的视野.所有这一切都将随着分子生物学技术的不断完善而付诸实现.     

耐药菌非抗生素疗法研究进展*

抗生素耐药性是21世纪人类面临的主要公共卫生威胁之一。抗生素滥用导致越来越多的细菌产生了耐药性,使得传统抗生素治疗面临着巨大挑战。非抗生素治疗策略,如噬菌体疗法、抗菌肽疗法、抗毒力因子疗法等,在应对耐药性细菌方面具有独特的优势与临床潜力,并且能够有效避免细菌耐药性的产生与传播。综述耐药菌非抗生素疗法的研究进展,探讨其在抗感染领域的新型治疗方案。未来,耐药菌非抗生素疗法有望协同乃至替代抗生素疗法,从而应对“抗生素危机”。     

光动力学疗法治疗肝胆肿瘤的研究现状

介绍了光动力学疗法治疗肝胆肿瘤的实验室和临床研究现状,提出了光动力学疗法在治疗肝胆肿瘤面临的问题,并建议在腹腔镜手术中引入光动力学疗法,认为随着新型光敏剂及光源的开发应用,PDT将会成为治疗肝胆肿瘤的切实可行方法。     

光动力疗法联合声动力疗法在抗肿瘤方面的研究进展

光动力疗法是一种使用光敏药物和激光活化治疗肿瘤疾病的方法.用特定波长的光辐照肿瘤部位,能使选择性聚集在肿瘤组织的光敏药物活化,引发光化学反应破坏肿瘤.然而,光动力疗法在临床上的应用却一直存在治疗深度受限的问题.本文分析了光动力疗法在临床应用中的局限性,并指出光动力疗法联合声动力疗法是一种可以克服光动力疗法治疗深度局限性...     

氧气雾化吸入疗法在老年喘息型支气管肺炎治疗中的价值探讨

目的探讨氧气雾化吸入疗法在老年喘息型支气管肺炎治疗中的价值。方法将90例老年喘息型支气管肺炎患者随机分为2组。对照组采用常规疗法即静脉点滴消炎、抗病毒、解痉平喘、祛痰药物及对症治疗。治疗组在上述常规疗法的基础上辅助应用氧气雾化吸入疗法。结果治疗组排痰效果、临床症状/体征消失时间明显缩短（P〈0.05,P〈0.01）。结论氧气雾化吸入疗法治疗老年喘息型支气管肺炎,改善症状疗效显著,起效快,用药少,操作简单,病人乐于接受,值得在基层医疗机构临床推广使用。     

肿瘤导向治疗的最新临床研究进展

20余年来,肿瘤的导向治疗研究经历了高潮和低潮的多次反复,终于在近几年取得了突破性进展,以Ritux-imab、Tractuzumab和DAB39IL-2为代表的抗肿瘤导向治疗制剂巳经通过FDA批准上市,展示出肿瘤导向治疗的光明前景。     

靶向肿瘤治疗的腺相关病毒载体

靶向性是肿瘤治疗取得成功的关键因素。病毒载体用于治疗肿瘤的过程中必须要求特异性作用于肿瘤细胞的同时降低对正常细胞的毒性。腺相关病毒(adeno-associated virus,AAV)较其他病毒载体具有免疫原性小、宿主范围广和介导基因可长期表达等优点,因此得到了广泛的应用。然而,AAV载体针对肿瘤的靶向性一直是近年研究的热点和难点。现就AAV载体治疗肿瘤的概况和靶向策略以及其安全性等方面作一综述。     

Targeting gene-virotherapy for cancer

Gene therapy and viral therapy for cancer have therapeutic effects, but there has been no significant breakthrough in these two forms of therapy. Therefore, a new strategy called “targeting gene-virotherapy”, which combines the advantages of gene therapy and viral therapy, has been formulated. This new therapy has stronger antitumor effects than either gene therapy or viral therapy. A tumor-specific replicative adenovirus vector ZD55 （E1B55KD deleted Adv.） was constructed and various single therapeutic genes were inserted into ZD55 to form ZD55-gene. These are the targeting gene-virotherapy genes. But experiments showed that a single gene was not effective in eliminating the tumor mass, and therefore two genes were separately inserted into ZD55. This strategy is called “targeting dual gene-virotherapy” （with PCT patent）. Better results were obtained with this strategy, and all the xenograft tumor masses were completely eliminated in all mice when two suitable genes producing a synergetic or compensative effect were chosen. Twenty-six papers on these strategies have been published by researchers in our laboratory. Furthermore, an adenoviral vector with two targeting promoters harboring two antitumor genes has been constructed for cancer therapy. Promising results have been obtained with this adenoviral vector and another patent has been applied for. This antitumor strategy can be used to kill tumor cells completely with minimum damage to normal cells.     

Targeting amino acid metabolism in cancer growth and anti-tumor immune response

Recent advances in amino acid metabolism have revealed that targeting amino acid metabolic enzymes in cancer therapy is a promising strategy for the development of novel therapeutic agents. There are currently several drugs in clinical trials that specifically target amino acid metabolic pathways in tumor cells. In the context of the tumor microenvironment,however,tumor cells form metabolic relationships with immune cells,and they oftencompete for common nutrients. Many tumors evolved to escape immune surveillance by taking advantage of their metabolic flexibility and redirecting nutrients for their own advantage. This review outlines the most recent advances in targeting amino acid metabolic pathways in cancer therapy while giving consideration to the impact these pathways may have on the anti-tumor immune response.     

Targeting gene-virotherapy of cancer

Our purpose is to completely elimination of xenograft tumor in animal tumor model in order to work out a protocal for the cure of patient. Gene therapy and viral therapy for cancer have got some therapeutic effects, but both have no great breakthrough. Therefore, we worked out a new strategy called Targeting Gene-Virotherapy of Cancer which is a combination of the advantage of gene therapy and virotherapy. This new strategy has stronger antitumor effect than either of them alone. A tumor specific replicative adenovirus vector ZD55 (E1B 55KD deleted Adv.) which is similar to ONYX-015 in targeting fuction but significant different in construction was produced and various single therapeutic gene was inserted into ZD55. Now such a conception as Targeting Gene-Virotherapy of Cancer was raised and systemically studied before, although there are some works on ONYX-015-tk, -cd or cd/-tk etc. separately. The antitumor effect of ZD55-Gene (for example IL-24 gene) is much better than ZD55 (virotherapy) alone and hundred fold high than that of Ad-IL-24 (gene therapy) alone. ZD55-IL-24 was in preclinal studying in the ZD55-IL-24 therapy, completely elimination of tumor mass was occurred in some mice but not in all mice, that means one gene was not effictive enough to eliminate all the tumor mass in all mice. Therefore two genes with compensative or synergetic effect were inserted into ZD55 separately and used in combination. This strategy was called Targeting Dual Gene-Virotherapy of Cancer (with PCT patent). Then much better results were obtained and all the xenograft tumor masses were completely eliminated in all mice, if two suitable genes were chosen. On the basis of the initiation of two gene results, it was thought about that using two tumors promoter to control the virus vector will be better for the targeting effect and the safty of the drugs. Then double tumor controlled virus vector harboring two genes for cancer therapy was worked out. Better results have been obtained and another patent has been applied. This antitumor strategy could be used to kill all the tumor cells completely in all mice with minimum damage to normal cells.     

增殖型腺病毒的改良及应用

增殖型腺病毒能在肿瘤细胞中复制并裂解肿瘤细胞,释放出的子代病毒再感染邻近肿瘤细胞直至完全杀灭肿瘤,却不影响正常细胞的功能。同时,增殖型腺病毒还是一种有效的基因治疗载体,可通过病毒自身增殖提高目的基因的拷贝数,从而更高效率地表达外源性治疗基因,增强抗肿瘤效应。本文着重介绍增殖型腺病毒载体改良和应用的最新进展,并对其研究前景进行展望,以期对增殖型腺病毒的发展有所帮助。     

Incorporation of adult organ-derived endothelial cells into tumor blood vessel

In this study, we attempted to assess the incorporable potential of vascular endothelial cells derived from adult organ blood vessels into tumor blood vessels. Two kinds of adult organ-derived vascular endothelial cells, human aorta endothelial cells (HAEC) and umbilical vein endothelial cells (HUVEC), were administered into murine tumors inoculated to SCID mice. Many human blood vessel networks were visualized in the murine tumors. These cells in solid tumor not only survived and proliferated, but also incorporated into tumor endothelium. These results suggest that adult organ-derived vascular endothelial cells possess the potential to form the neovascular network in various tissues such as vascular endothelial progenitor-like cells in vivo. We propose that these cells can be regarded as a congenic (autologous) vector for vascular regeneration cell therapy and tumor vascular targeting gene therapy.     

Bio and nanotechnological strategies for tumor-targeted gene therapy

Gene therapy is a new medical approach for the treatment of tumors. For safe and efficient gene therapy, therapeutic genes need to be delivered efficiently into the target tumor cells. Development of gene delivery systems to specifically recognize and target tumor cells and to distinguish them from normal cells, especially in the same tissue or organ, is one of the most important issues regarding the present gene delivery methodologies. The enhanced permeability and retention (EPR) effect using the characteristics of angiogenic tumor blood vessels, as well as gene delivery systems recognizing hyperactivated receptors or intracellular signals, is broadly applied to tumor-targeted gene therapy. In addition, bacterial vectors can be a useful means for targeting hypoxic or anoxic regions of a tumor.     

分子靶向治疗在前列腺癌中的研究进展

前列腺癌是目前在全球男性中第二位最常见的肿瘤,其在恶性肿瘤死亡率中排名第六位[1]。在发病率方面,我国虽然不及西方国家,但是随着生活水平和诊疗技术的提高,也表现出了逐渐上升的态势。靶向治疗是以肿瘤细胞的特有位点作为治疗靶点,在纠正病变、稳定细胞、发挥更强的抗肿瘤活性的同时,能够对正常细胞减少毒副作用[2]。由于我们对于肿瘤发生发展的分子途径认知的逐渐提高,以及更好的利用这些途径作为有效的药物作用靶点,我们已经看到了越来越多的分子靶向药物的开发和生产随之增加。本文着重探讨了分子靶向药物对肿瘤的治疗起作用的不同的靶向机制,以及它们的研究现状及临床应用。     

瞄准肿瘤干细胞多药耐药性基因的靶向治疗策略

肿瘤干细胞(TSC)的学说得到了越来越多人的认可,而且多种TSC已被鉴定。当前TSC研究的重点之一是靶向治疗问题。有多项实验结果支持,TSC高表达ABC转运体是其多药耐药性的重要原因,因此,靶向TSC的ABC转运体在肿瘤化疗中起着关键作用。我们总结了靶向治疗TSC的ABC转运体的研究概况、存在问题及解决策略,以期在该领域研究能有更快进展。     

靶向CCL21/CCR7轴治疗肿瘤转移的研究进展

转移是肿瘤患者死亡最常见的原因,而淋巴转移是大多数肿瘤转移的主要途径之一。近年来,CC趋化因子配体21 (CC chemokine ligand 21,CCL21) 及其受体CC趋化因子受体7型 (CC chemokine receptor type 7,CCR7) 在淋巴转移中的作用逐渐受到关注。CCL21主要由淋巴内皮细胞产生,其与树突状细胞 (Dendritic cells,DCs) 和T细胞等表面CCR7的相互作用是免疫细胞淋巴迁移及淋巴结归巢的主要决定因素。然而,表达CCR7的肿瘤细胞也可以利用类似的机制进入淋巴管进行淋巴转移。如何靶向CCL21/CCR7轴,既能抑制淋巴转移,又不影响抗肿瘤免疫反应已成为肿瘤免疫治疗研究的重要议题。文中将对CCL21/CCR7轴在淋巴转移中的作用及其作为靶点治疗肿瘤转移的临床前和临床试验研究进行综述,为靶向CCL21/CCR7信号轴治疗肿瘤转移的相关研究提供参考。