Xenogeneic homologous genes, molecular evolution and cancer therapy

Cancer is one of the main causes for death of human beings to date, and cancer biotherapy (mainlyimmunotherapy and gene therapy) has become the most promising approach after surgical therapy, radiotherapy andchemotherapy. However, there are still many limitations on cancer immunotherapy and gene therapy; therefore great ef-fort is being made to develop new strategies. It has been known that, in the process of evolution, a number of genes, theso-called xenogeneic homologous genes, are well-conserved and show the structural and/or functional similarity betweenvarious species to some degree. The nucleotide changes between various xenogeneic homologous genes are derived frommutation, and most of them are neutral mutations. Considering that the subtle differences in xenogeneic homologousgenes can break immune tolerance, enhance the immunogenicity and induce autologous immune response so as to elimi-nate tumor cells, we expect that a strategy of inducing autoimmune response using the property of xenogeneic homologousgenes will become a new therapy for cancer. Moreover, this therapy can also be used in the treatment of other diseases,such as autoimmune diseases and AIDS. This article will discuss the xenogeneic homologous genes, molecular evolutionand cancer therapy.     

功能磁共振用于肿瘤光热和光动力协同治疗的实时监测研究

将实验动物分为光热治疗组、光动力治疗组、光热和光动力协同治疗组,使用T2加权和扩散加权两种磁共振成像方式对治疗效果进行实时监测,并使用病理学方法对磁共振检测效果进行验证.实验结果发现,两个单纯治疗组中肿瘤并未被完全杀灭;而协同治疗组中,肿瘤被完全杀灭.磁共振作为无创监测手段,在疗效评价中有巨大的应用价值,并可对纳米粒子的设计合成起到指导作用.     

化疗联合放疗治疗中晚期贲门癌的临床观察

目的 :观察化疗联合放疗治疗中晚期贲门癌的疗效 ,探讨更有效的治疗方式。方法 :46例中晚期贲门癌患者均分至 2个组 ,单放组采用常规分割 ,DT5 0 GY/5周。综合组采用化疗 +放疗 +化疗 ,化疗采用 FP方案 ,前后各 2个周期。结果 :2个组治疗后完全缓解率 :单放组为 0 ,综合组为1 2 .6%。病情进展率 :单放组为 1 8% ,综合组为 4.3%。 2个组近期疗效差异有显著性意义 ( x2 =4.39,P<0 .0 5 ) ,综合组副作用大于单放组 ,( t=4.31 8,P<0 .0 1 ) .结论 :化疗联合放疗可提高局部控制率 ,改善患者生存质量 ,提高疗效 ,毒副反应可耐受     

光动力疗法诱导的免疫原性细胞死亡的研究进展

光动力疗法（PDT）已被证明可以诱导免疫原性细胞死亡（ICD）.但是由于PDT本身的局限性以及肿瘤部位的免疫原性差和免疫抑制环境的原因，单独的PDT在癌症免疫治疗中难以获得强大而持久的适应性抗肿瘤功效，往往需要采用不同的策略来提高肿瘤的免疫应答效果.因此，文章简述了光动力学机理、ICD原理，以及对PDT诱导的ICD的各种不同策略进行了总结和讨论，策略包括增加氧气（O₂）和靶向性提高PDT效果，PDT联合光热疗法（PTT）和化疗等治疗方式，PDT结合免疫检查点以及免疫佐剂抑制来提高ICD效应，以此为研究人员提供更多的癌症免疫治疗方面的参考.     

放射治疗中自适应技术研究进展

 介绍自适应放射治疗方案的提出背景及其基本理念。通过分析离线自适应方案和在线自适应方案的应用,阐述了自适应放射治疗的基本实施方法及不同的实施方案特点和优劣。进一步综述了当前国内外一些相关研究的成果,着重介绍了其在鼻咽癌、宫颈癌、前列腺癌等方面的研究进展以及各种软硬件技术的可行性及效用。认为当前的研究成果已证明了自适应放射治疗技术在肿瘤放疗中的应用价值,未来该技术的发展方向应是进一步研究完善技术规范,从而推广其在临床中的应用。     

Synthesis of pH-responsive supramolecular polypeptide nanoparticles from α-amino acids for combined chemo-photothermal therapy

A new smart supramolecular polypeptide copolymer P(Glu-co-Lys) was synthesized by the polymerization of α-amino acids using the N-thiocarboxylic acid anhydride (NTA) method, using the pH dynamic response peptide of L-glutamic acid and L-lysine as a carrier for tumor cells. The drug delivery system activated by external acid can self-assemble (pH 7.4) and disassemble (pH 5.5) under the adjustment of pH to load the drug and control its release. Doxycycline (DOX) and the photothermal reagent hydrophilic quanternary stereo-cyanine (HQS-Cy) were loaded into the peptide copolymer to obtain HQS-Cy/DOX nanoparticles (NPs) for chemo-photothermal therapy. Gentle photothermal heating can enhance the absorption of drugs by cells and enhance the efficacy of chemotherapy. In addition, chemo-photothermal therapy can solve the defect of easy recurrence after single photothermal therapy. The ingenious nanodrug delivery system of HQS-Cy/DOX NPs provides great potential for the improvement of chemo-photothermal therapy and will achieve excellent therapeutic effects in cancer treatment.     

HIV chemotherapy

The use of chemotherapy to suppress replication of the human immunodeficiency virus (HIV) has transformed the face of AIDS in the developed world. Pronounced reductions in illness and death have been achieved and healthcare utilization has diminished. HIV therapy has also provided many new insights into the pathogenesis and the viral and cellular dynamics of HIV infection. But challenges remain. Treatment does not suppress HIV replication in all patients, and the emergence of drug-resistant virus hinders subsequent treatment. Chronic therapy can also result in toxicity. These challenges prompt the search for new drugs and new therapeutic strategies to control chronic viral replication.     

硫属铜基诊疗试剂的研究进展

基于近红外光热治疗的诊疗一体化技术是一种新兴的具有广阔应用前景的癌症治疗方法.它可以通过对肿瘤的可视化检测分析,进而实施个体差异化治疗.硫属铜基纳米材料具有强近红外吸收、高光热转换效率、廉价以及制备方法简单等诸多优点,因此基于该类材料的癌症诊疗一体化成为了近些年的研究热点.介绍了近年来硫属铜基纳米材料在癌症诊断、治疗以及一体化上的最新研究进展.     

卟啉MOFs材料应用于肿瘤治疗领域的研究进展

卟啉类化合物因其独特的物理和化学特性,在肿瘤治疗领域具有广阔的应用前景.但是卟啉类化合物存在水溶解性较差和易于自聚集等缺点,限制了其在肿瘤治疗上的广泛应用.而金属有机框架（MOFs）具有可调节孔径、可功能化修饰,以及生物相容性好等优点.因此,将卟啉作为有机连接体,结合金属簇构建卟啉MOFs材料,不仅可以克服卟啉类化合物固有的缺点,而且还能发挥MOFs的优异特性.文章综述了近年来卟啉MOFs材料的合成方法及其在肿瘤治疗方面的研究进展,同时探讨了其在肿瘤治疗领域的挑战.     

Capsid modification of adeno-associated virus and tumor targeting gene therapy

Targeting is critical for successful tumor gene therapy. The adeno-associated virus （AAV） has aroused wide concern due to its excellent advantages over other viral vectors in gene therapy. AAV has a broad infection spectrum, which also results in poor specificity towards tissues or cells and low transduction efficiency. Therefore, it is imperative to improve target and transduction efficiency in AAV-mediated gene therapy. Up to now, researchers have developed many strategies to modify AAV capsids for im- proving targeting or retargeting only desired cells. These strategies include not only traditional chemical modification, phage display technology, modification of AAV capsid genome, chimeric vectors and so on, but also many novel strategies involved in marker rescue strategy, direct evolution of capsid proteins, direct display random peptides on AAV capsid, AAVP （AAV-Phage）, and etc. This review will summarize the advances of researches on the capsid modification of AAV to target malignant cells.     

癌症诊疗一体化研究进展

 癌症诊疗一体化是集癌症诊断和治疗于一体的新技术。通过将具有肿瘤诊断和治疗功能的组分同时整合到一个纳米平台上,获得纳米诊疗剂,有望实现肿瘤的早期诊断、精确定位、原位治疗,以及实现在治疗过程中的实时疗效监测与预后。本文概述了癌症诊疗一体化的发展历程,分析了诊疗一体化在癌症诊断和治疗过程中的独特优势,介绍了具有代表性的纳米诊疗剂,展望了癌症诊疗一体化领域未来的发展方向。     

纳米材料在基因治疗中的研究进展:从肿瘤治疗到新冠病毒疫苗

基因治疗作为一种精准有效的策略,可用于治疗包括癌症在内的多种疾病以及预防病毒性感染疾病．然而,基因治疗中使用的核酸药物自身不稳定性和大尺寸阻碍了它们的广泛应用．纳米材料因其免疫原性低、可控性好、易于进行表面修饰等特点,已被证明是基因治疗中最有前途的载体之一．特别是新型冠状病毒肺炎（COVID-19）疫情爆发以来,与传统疫苗不同的mRNA疫苗备受关注,而脂质纳米颗粒（LNP）作为该疫苗的递送系统发挥了至关重要的作用,展现了纳米材料巨大的应用前景．本文概述了基因治疗的主要类型;介绍了基于脂质的纳米颗粒、基于聚合物的纳米颗粒、无机纳米颗粒及新型纳米材料如碳点等核酸递送平台;强调了其在肿瘤治疗和COVID-19核酸疫苗中的最新研究进展;提出了纳米材料用于基因治疗的挑战与前景．      

Development of a nano-immunomodulator encapsulating R837 and caffeine for combined radio-/immunotherapy against orthotopic breast cancer

Immunotherapy is an ascendant approach in cancer treatment. It shows more pronounced effects on killing cancer cells in a specific manner in particular against metastasis more than traditional techniques, such as chemotherapy or surgery. However, tumor immunosuppression limits the response of the immune system to cancer development. In this study, we developed a lipid-based nanocarrier doubly loaded with imiquimod (R837), a toll-like receptor 7 agonist, and caffeine, an adenosine receptor antagonist. This R837/caffeine loaded nanocarrier served as a nano-immunomodulator (RC-nIM) for combination treatment with radiotherapy (RT) against orthotopic breast cancer. RT-induced immunogenic cell death facilitated the production of tumor antigen and elicited the immune response in corporation with R837-medaited activation of antigen-presenting cells (APCs) while RC-nIMs being adopted. Additionally, caffeine, an adenosine analog, can successfully compete with adenosine in the tumor. The tumor-bearing mice that received RT together with RC-nIMs experienced the best antitumor effects and exhibited higher levels of T cells and APCs within the tumor; the growth of secondary tumors was also limited. This work serves as a proof-of-concept study for the development of a new immunotherapy strategy against cancer.     

氧化铈纳米材料的合成及其在癌症治疗方面的研究进展

近年来，氧化铈纳米颗粒（CeO₂NPs）材料的合成及其在生物医学，尤其是在癌症治疗方面的应用研究引起了研究者们的广泛关注.一方面，CeO₂NPs对癌细胞具有明显的细胞毒性，能用于光动力治疗（PDT）和化学药物治疗（CHT）等方面，并且能够使癌细胞对放射治疗（RT）敏感；另一方面，CeO₂NPs能保护正常细胞，具有抗氧化活性.这种具有差异细胞毒性的材料为开发新型癌症治疗试剂提供了新的思路.文章系统地介绍了近年来CeO₂NPs的合成及其在癌症治疗方面的研究进展，希望对该材料将来的研究工作起到一定推动作用.     

Preparation,characterization and release of methyl viologen from a novel nanoparticle delivery system with double shells of silica and PLGA

The use of nanotechnology in drug delivery is a rapidly expanding field. Biodegradable or nontoxic nanomaterials have the most promising application potentials in nanomedicine. Herein, we report a novel core-shell nanoparticle with double shell coatings (silica and poly(D,L-lactide-co-glycolide) (PLGA)) with the total shell thickness of (8.7 ± 1.3) nm. The outer shell of PLGA is biodegradable and used for controlled and sustained release, and the inner shell of silica is mesoporous for the preservation of t...     

TNF基因治疗肿瘤的研究进展

肿瘤坏死因子 (TNF)是一种既能直接杀死肿瘤细胞 ,又能通过激活免疫系统发挥抗肿瘤作用的细胞因子 .其基因工程药品临床应用后 ,具有严重的毒副作用 ,因此 ,人们开始了TNF基因冶疗的研究 .TNF基因治疗为TNF在肿瘤治疗中的应用开拓了新的途径     

纳米技术在抗肿瘤药物靶向递释系统中的应用研究进展

 纳米载药技术已经在抗肿瘤药物递送领域受到广泛关注。纳米技术可以显著增加难溶性药物的生物利用度,改善药物释放与摄取行为,提高药物对肿瘤组织的靶向性,增加药物在肿瘤组织的分布与蓄积,降低药物对正常组织和细胞毒副作用,实现减毒增效。尽管如此,如何有效克服肿瘤生理屏障,进一步提高化疗药物的肿瘤特异性,实现肿瘤组织深度渗透和肿瘤细胞内可控释药仍然是开发抗肿瘤纳米药物亟需解决的重大挑战。从被动靶向、物理靶向、主动靶向和仿生靶向4个方面概述了纳米载药系统抗肿瘤药物在克服肿瘤屏障实现肿瘤靶向药物递送方面的研究进展。     

单基因遗传疾病的基因疗法

 基因疗法是全球突破性技术之一，在单基因遗传疾病治疗中已取得突破性进展。阐述了不同的基因疗法策略、载体和基因编辑技术的特点，综述了脊髓性肌萎缩症、Leber先天性黑蒙2型、血友病、β-地中海贫血的发病机理、临床表现、基因疗法的开发进程以及临床试验情况。目前，上述4种单基因疾病的9种基因疗法已分别取得美国食品药品监督管理局突破性疗法资格、欧洲药品管理局的优先药物资格或者已经批准上市。基因疗法的研究还面临着许多挑战，但随着科学研究的深入和科学技术的不断发展，将有更多的患者获得治疗。     

Mechanisms of drug inhibition of signalling molecules

The emergence of tumour-specific, molecularly targeted agents signifies a paradigm shift in cancer therapy, with less reliance on drugs that non-discriminately kill tumour and host cells. Although the diversity of targets giving rise to this new generation of anticancer drugs has expanded, many challenges persist in the design of effective treatment regimens. The complex interplay of signal-transduction pathways further complicates the customization of cancer treatments to target single mechanisms. However, despite uncertainty over precise or dominant mechanisms of action, especially for compounds targeting multiple gene products, emerging agents are producing significant therapeutic advances against a broad range of human cancers.     

原发性肝癌三维适形和调强放疗的基础和临床研究

报告三维适形（3-dimensional conformal radiation therapy, 3DCRT）和调强放疗（intensity-modulated radiation therapy, IMRT）治疗原发性肝癌（HCC）的基础和临床研究,建立了3DCRT和IMRT放疗HCC的技术,进行3个临床试验,获得了令人鼓舞的3年总生存率：28 ％～33 ％。治疗并发症主要是放射性肝病（RILD）,此并发症的死亡率为76 ％,预防RILD最有效的方法是把对正常肝脏的放射剂量限制在安全的范围内。我国的HCC病人大都伴有肝硬化,伴发的肝硬化损害了肝脏对放射损伤的修复和肝脏再生的能力,他们的放射耐受剂量是（全肝平均剂量）：Child-Pugh A病人23 Gy,Child-Pugh B病人6 Gy,这个耐受量显著低于目前国际上通用的30 Gy。研究建立了用于预测我国HCC病人放疗中发生RILD发生概率的Lyman数学模式,其参数明显不同于国外的模式,并将一整套适合我国国情的HCC放疗技术成功地进行了临床实践,证实了放疗可以作为不能手术肝癌的一种治疗选择。