Gene Therapy of Cancer： Induction of Anti-Tumor Immunity

Many malignancies lack satisfactory treatment and new therapeutic options are urgently needed. Gene therapy is a new modality to treat both inherited and acquired diseases based on the transfer of genetic material to the tissues. Different gene therapy strategies against cancers have been developed. A considerable number of preclinical studies indicate that a great variety of cancers are amenable to gene therapy. Among these strategies, induction of anti-tumor immunity is the most promising approach. Gene therapy with cytokines has reached unprecedented success in preclinical models of cancer. Synergistic rather than additive effects have been demonstrated by combination of gene transfer of cytokines/chemokines, costimulatory molecules or adoptive cell therapy. Recent progress in vector technology and in imaging techniques allowing in vivo assessment of gene expression will facilitate the development of clinical applications of gene therapy, a procedure which may have a notorious impact in the management of cancers lacking effective treatment.     

The National Stem Cell Therapy Patient Registry of Malaysia—Measuring Clinical Outcomes of Stem Cell Therapy

Very few registries worldwide focus on clinical outcomes of stem cell therapy (SCT) as the large number of applications and rapid development of the field complicates registry design considerably. The National Stem Cell Therapy Patient Registry of Malaysia aims to accommodate this by using a main protocol which covers the overall design and administration of the registry, and condition-specific sub-protocols which deal with outcome measures. The registry will start with a few sub-protocols covering existing modes of SCT in Malaysia, with new sub-protocols released periodically as the need arises.     

Search for “Weapons of Mass Destruction” for Cancer - Immuno/ Gene Therapy Comes of Age

The complexity of a cancer, such as cell heterogeneity, and the existence of hypoxia, stromai cells and stem cells has so far prevented successful development and treatment of patients suffering from the later stages of cancers. At present, the use of conventional therapies, such as chemo/radio therapy is limited, and only therapies that are focused on utilizing the patient＇s immune response to combat against the disease appear to be the most reliable and promising. Two decades ago, cytokines were discovered to be able to activate the immune systems and mount an anti-tumour response. Then, dendritic cells were hailed as the most significant regulators of immunity and are employed in a variety of cancer management schemes. This review introduces current development in the field, focusing on combination of the components of ＇he rapidly growing fields of immunotherapy and gene transfer/therapy, providing useful and significant detailed information for readers of cellular and molecular immunology.     

Gene and transgenics nomenclature for the laboratory axolotl—Ambystoma mexicanum

The laboratory axolotl (Ambystoma mexicanum) is widely used in biological research. Recent advancements in genetic and molecular toolkits are greatly accelerating the work using axolotl, especially in the area of tissue regeneration. At this juncture, there is a critical need to establish gene and transgenic nomenclature to ensure uniformity in axolotl research. Here, we propose guidelines for genetic nomenclature when working with the axolotl.     

Targeted Therapy—Possible New Therapeutic Option for Malignant Mesothelioma?

Malignant Mesothelioma presents with a characteristic heterogeneous growth pattern. Response to treatment is often only partial, which may be related to tumor cell heterogeneity. Molecular screening methods have revealed profound differences in the driving mechanisms of the variously differentiated mesothelioma cells. Characterization of these differences has made it possible to identify novel drug targets which are effective for both phenotypes.     

Soluble TNF-�� Receptor I Encoded on Plasmid Vector and Its Application in Experimental Gene Therapy of Radiation-Induced Lung Fibrosis

Post-radiation inflammatory reaction leads to an irreversible pulmonary fibrosis which may cause lethal respiratory insufficiency. Pathological inflammatory and fibrotic changes might be attenuated by inhibiting tumour necrosis factor (TNF)-α activity using TNF-α soluble receptors. Thus, an experimental antifibrotic gene therapy with the plasmid vector encoding a mouse soluble receptor I for TNF-α (psTNFR-I) was assessed. Soluble TNFR-I encoding gene was cloned into pcDNA3.1 plasmid. The ability of psTNFR-I expressing vector to transfect cells, and its biological activity in vitro and in vivo were examined by PCR, RT-PCR, MTT assay and ELISA. The C57Bl/6J mice received single intramuscular injection of psTNFR-I, conjugated with polyetylenimine (PEI) 25 kDa, equally divided to both hind legs, 3 days before irradiation (20 Gy, Co60), and either a single injection or ten injections once a week after irradiation. The data proved the effectiveness of psTNFR-I product to neutralise TNF-α activity in vitro. The in vivo plasmid incorporation and maintenance was confirmed. Measurements of plasma soluble TNFR-I levels showed that the in vivo gene transfer was effective. PEI was found to enhance transfection efficiency in vivo. The psTNFR-I/PEI complexes caused no toxicity in the transfected mice. C57Bl/6J mice that received prolonged psTNFR-I/PEI injections developed lethal fibrotic syndrome and died 8 weeks later than the mice treated with a double plasmid injection and the control mice treated with a control plasmid. Sequential administration of soluble TNFR-I by a nonviral, intramuscular gene transduction in the early and late post-radiation inflammatory phase prolonged survival of irradiated mice and attenuated the symptoms of lung fibrosis. The psTNFR-I gene transduction may provide a safe and simple method to partially neutralise TNF-α activity and prevent radiation-induced lung injury.     

4—1BBL研究进展

4—1BBL属于肿瘤坏死因子配体超家族，它所介导的协同刺激信号可促进T淋巴细胞的活化、增殖、分化，在免疫应答、免疫调节以及肿瘤、病毒感染、移植排斥的免疫治疗等方面发挥了重要的作用。对4—1BBL的深入研究，为探索免疫应答的机理以及通过调控免疫应答来治疗某些疾病提供了新的思路和方法。     

CTLA—4的研究进展

CTLA－4作为一T细胞活化的负性调节分子，在自身免疫性疾病和异种移植排斥过程中起着重要的作用，因而受到广泛的注意，它不但与Th1/Th2的分化有关，还参与T细胞无能的诱导过程，其对T细胞活化的抑制作用与其结构功能有着密切的关系。     

联合检测血清FGF-21、RBP4、SF水平在2型糖尿病评估中的价值研究

目的探究并分析联合检测血清人成纤维细胞生长因21 (FGF-21)、重组人视黄醇结合蛋白-4(recombinant human retinol binding protein-4,RBP4)、血清铁蛋白(serum ferritin,SF)水平在2型糖尿病(type 2 diabetes,T2DM)评估中的价值。方法选取2016年6月至2017年6月我院收治的2型糖尿病患者48例,作为T2DM组;同时选取34例糖耐量异常(impaired glucose tolerance,IGT)患者,作为IGT组,另选取我院进行体检的健康志愿者30例,作为对照组。观察并记录各组受试者FGF-21、RBP4、SF水平,比较其在不同组之间的表达情况。分析并比较单独FGF-21、RBP4、SF以及联合FGF-21、RBP4、SF检测对2型糖尿病的评估效果。采用ROC曲线分析各方法的评估效率。结果 T2DM组血清FGF-21、RBP4、SF水平显著高于IGT组和健康人群(P <0.05),而IGT组患者FGF-21、RBP4、SF水平显著高于健康人群(P<0. 05);用单独的FGF-21、RBP4、SF检测进行评估,特异性差异具有统计学意义(P <0.05),其中,RBP4评估的特异性显著高于FGF-21、SF的评估特异性(P<0.05);对于平行联合检测,FGF-21+RBP4+SF评估的灵敏度、阴性预测值均显著高于FGF-21+SF、RBP4+SF(P<0.05);对于系列联合检测,FGF-21+RBP4+SF评估的特异性显著高于FGF-21+SF(P<0.05);采用FGF-21+RBP4+SF评估时,系列联合检测的灵敏度显著低于平行联合检测(P <0.05),特异性显著高于平行联合检测(P<0.05);FGF-21+SF、RBP4+SF及FGF-21+RBP4+SF评估T2DM,平行联合检测ROC曲线下面积分别为0.761、0.763和0.915,系列联合检测ROC曲线下面积为0.750、0.721和0.904,FGF-21+RBP4+SF评估的ROC曲线下面积显著高于FGF-21+SF、RBP4+SF(P<0.05),具有统计学意义。结论 FGF-21+RBP4+SF联合检测评估效率显著高于各单项检查,能有效提高糖尿病评估灵敏度、特异性及准确率,值得临床推广。     

AIDS新疗法——抗体-CD4杂交分子

以前,AIDS的治疗主要是药物(如AZT等)疗法。然而,血液中出现了AZT耐受性免疫缺陷病毒(HIV)。尔后发现HIV主要与免疫细胞表面的CD4分子结合,从而攻击免疫系统。科学家把可溶性CD4分子注入AIDS患者血液中,可以中和HIV的CD4结合部位,从而可以预防HIV未与免疫细胞接触的个体。     

The “Editors” Take to RAG: Promise of CRISPR/Cas9/rAAV6-Based Gene Therapy for RAG2 Deficiency

Journal of Clinical Immunology -     

4—4 放射治疗食管癌非模拟机定位方法探讨

虽说摸拟定位机已进入临床应用。但在国内尚未普及,我们利用直角三角形的几何原理,借助普通X线诊断机在一张X光片上拍摄双重食管影像的方法,解决了食管癌交角布野定位的问题,临床应用1200例,效果满意,方法如下: 1.首先在透视下直接标出胸前后背部垂直野的纵横中心交点(这里的背部野仅作计算交叉野旁开距和布交叉野时参考用)。 2.置患者于摄影床上,a平躺仰卧、紧贴背部放一装有X光胶片的暗盒。然后(以     

Gene polymorphisms of interleukin-4, interleukin-10 and transforming growth factor-beta in Graves’ disease

Among genetic factors that may contribute to the development and progression of Graves’ disease (GD) and its complications are polymorphisms in the genes encoding cytokines. The association between GD and the following polymorphisms in anti-inflammatory cytokines was studied in 107 patients with GD and 140 healthy controls: IL-4 (−1098T/G, −590T/C, −33C/T), IL-10 (−1082A/G, −819C/T, −592C/A) and TGF-β (+869T/C, +915G/C). The following alleles and genotypes were significantly (P < 0.01 after correction for multiple testing) more frequent among patients: the IL-4 −1098G allele and GG genotype (OR = 3.12 and 105.00, respectively), IL-4 −33T allele and TT genotype (OR = 2.52 and 118.83, respectively), IL-10 −1082G allele and GG genotype (OR = 2.16 and 6.40, respectively), IL-10 −819T allele, TC and TT genotype (OR = 2.60, 3.68 and 6.76, respectively), IL-10 −592A allele, AC and AA genotype (OR = 2.41, 2.89 and 5.68, respectively), TGF-β +869C allele and CC genotype (OR = 2.24 and 6.21, respectively), and TGF-β +915C allele, CG and CC genotype (OR = 7.81, 11.80 and 20.40, respectively). The only allele and genotype with a lower frequency in patients were IL-4 −590T allele and TC genotype (OR = 0.47 and 0.08, respectively; P < 0.01). In conclusion, this study highlighted the importance of anti-inflammatory cytokine gene polymorphisms in susceptibility to GD.     

共刺激分子：4—1BB和4—1BB配体的研究进展

4-1BB和4-1BB配体(4-1BBL)属于肿瘤坏死因子，月中瘤坏死因子受体(TNF/TNFR)超家属成员。近年研究发现，4-1BB和4-1BBL相互作用产生的共刺激信号在机体免疫应答，如肿瘤免疫、移植免疫等中起重要作用。因此，调节4-1BB/4-1BBL信号有望成为临床治疗恶性肿瘤(特别是低免疫原性肿瘤)和器官移植等所致的免疫功能紊乱的有效手段之一。     

人PBL及CTLL—2／HIL—4R细胞系对人IL—4增殖应答的特性

本文分析了３０例正常人ＰＲＬ经ＰＨＡ活化的Ｔ细胞对ＩＬ－２及ＩＬ－４的增殖应答特点；及整合有人ＩＬ－４受体ｃＤＮＡ的ＣＴＬＬ－２／ＨＩＬ－４Ｒ细胞系对人ＩＬ－４的特异增殖应答特点。结果表明，正常人经ＰＨＡ活化的ＰＢＬ对ＩＬ－２有良好增殖应答曲线者占９３％，而对ＩＬ－４有良好增殖应答者只占２０％。　ＣＴＬＬ－２／ＨＩＬ－４Ｒ细胞系对人ＩＬ－４呈规律性增殖应答曲线，且应答敏感性高，可测出０．０９ｕ／ｍｌ，可推荐作为测定人ＩＬ－４生物活性的一种准确方法。     

白介素—4受体信号转导研究进展

白介素4（IL－4）是Th2型的多效性细胞因子,其生物活性的发挥是通过白IL－4受体（IL－4R）完成的。IL－4胞内信号转导途径主要有4条：IRS－1／2途径、PI3K途径、Ras途径以及Jak-STAT途径。本文主要就IL－4R的信号转导及调节机制的研究进展作一综述。