肝癌的免疫基因治疗

免疫基因治疗主要通过加强肿瘤细胞的免疫原性或机体免疫效应细胞的效应性达到治疗的目的 ,随着研究的深入 ,许多成果从实验室走向了临床。笔者从免疫效应细胞和肿瘤细胞两个角度 ,对肝癌免疫基因治疗予以综述。1　针对免疫效应细胞的治疗利用基因工程技术 ,将细胞因子基因导入免疫效应细胞 ,当效应细胞回输体内时 ,细胞因子以自分泌或旁分泌方式在局部达到较高浓度 ,从而协同免疫细胞发挥抗肿瘤效应。淋巴因子激活的杀伤细胞 (ＬＡＫ细胞 )和白介素 2 (ＩＬ 2 )的联合应用已在多种肿瘤治疗中取得了一定效果。肿瘤浸润淋巴细胞 (ＴＩＬ)因…     

乳腺癌的基因治疗与核素靶向治疗

乳腺癌的基因治疗是近年来肿瘤治疗研究的热点,目前处于实验或临床初步应用的基因治疗方法主要有免疫基因治疗、多药耐药基因治疗、反义寡核苷酸治疗、自杀基因治疗等方法,而将基因治疗与射核素相结合的基因靶向近距离放射治疗的方法具有放射性核素与自杀基因对肿瘤细胞的双重杀灭作用,为肿瘤基因治疗开辟了一条崭新的途径,在这一领域进一步研究必将加快基因靶向治疗向临床应用迈进的步伐。     

乳腺癌的基因治疗与核素靶向治疗

乳腺癌的基因治疗是近年来肿瘤治疗研究的热点，目前处于实验或临床初步应用的基因治疗方法主要有免疫基因治疗、多药耐药基因治疗、反义寡核苷酸治疗、自杀基因治疗等方法，而将基因治疗与放射性核素相结合的基因靶向近距离放射治疗的方法具有放射性核素与自杀基因对肿瘤细胞的双重杀灭作用，为肿瘤基因治疗开辟了一条崭新的途径，在这一领域进一步研究必将加快基因靶向治疗向临床应用迈进的步伐。     

肝癌基因治疗研究进展与介入医学

目前研究表明肝癌的发生是一个多步骤的复杂过程 ,在这个过程中 ,有多种癌基因和抑癌基因的改变 ,肝癌的癌基因谱已逐渐明朗。肝癌的基因治疗是目前学术界研究的热点 ,已取得了很大的进展。本文综述肝癌基因治疗的研究进展并对介入医学在肝癌基因治疗中的地位和作用作一展望。癌基因治疗策略肝癌是多基因突变引起的 ,基因治疗的原则、目的和基因的选择比较复杂 ,常用的肝癌基因治疗策略有以下几类。1.免疫性基因治疗现代肿瘤免疫学认为恶性肿瘤的发生是恶性转化细胞逃避了机体的免疫监视 (免疫逃逸 ) ,从而在机体内自主快速生长的结果。肿瘤…     

基因治疗与影像学

在临床医学研究领域 ,基因治疗代表了令人振奋的前沿 ,基因治疗的研究正在飞速地发展。到目前 ,外源基因的表达多是通过体外的实验来检测 ,比如聚合酶链反应、原位杂交和免疫组织化学染色等。但随着基因治疗从基础走向临床 ,这些体外方法显示了较大的缺陷 ,即在临床试验中 ,不能无创、动态地获知转基因表达的部位、幅度和时间。因此 ,如何用体外的成像方法来监测转入基因的表达 ,这是基因治疗大规模进入临床试验前必须解决的问题。新近在影像技术方面的发展和突破 ,有望解决如上问题。放射学家只有熟悉基因治疗的原理、策略和新进展 ,才能跟…     

肿瘤基因治疗的研究进展和展望

肿瘤的基因治疗策略主要有两条途径[1] :一是常规途径 ,即我们通常所说的基因治疗 ,包括免疫基因治疗、增强药物敏感性、转导耐药基因以减少大剂量化疗药物毒性、肿瘤抑制基因治疗等。目前主要着眼于肿瘤浸润淋巴细胞(ＴＩＬ)、肿瘤细胞、成纤维细胞、树突状细胞(ＤＣ)表达细胞因子的方面。其次是通过自体肿瘤细胞导入细胞因子后制成肿瘤疫苗。为克服肿瘤细胞来源及细胞因子可能不表达的困难 ,可以增强肿瘤细胞的免疫原性 ,也可注射导入细胞因子基因的成纤维细胞。目前肿瘤基因治疗的研究已从实验室基础研究阶段发展到临床应用阶段。本文将…     

骨肉瘤基因治疗及载体系统研究现状

近年来,有关骨肉瘤基因治疗的研究在基因治疗方法、基因载体、载体导入途径等方面取得了较大进展。骨肉瘤的基因治疗主要有免疫基因治疗、反义基因治疗、抑基因治疗、自杀基因治疗及联合基因治疗等。基因载体包括病毒载体和非病毒载体。     

p53基因在肝细胞癌治疗中的现状与展望

p53基因突变可以引起细胞转化,导致癌变.通过特异性途径及载体人工导入野生型P53基因可以使肿瘤局部高表达野生型p53基因.野生型p53基因具有抑制肿瘤细胞增殖、诱导肿瘤细胞凋亡的功能,从而达到治疗恶性肿瘤的目的 .目前,p53基因治疗肝细胞癌的实验及临床应用也取得了一定的成绩.就p53基因治疗肝细胞癌的现状及进展情况予以综述.     

肿瘤细胞因子基因治疗的研究现状

1　概述 　　细胞因子基因治疗肿瘤也称为免疫基因治疗［1］，是应用分子生物学方法，将与免 疫有关的细胞因子基因转导入肿瘤或其它免疫效应细胞，使其在机体表达分泌细胞因子或利 用其实基因增强肿瘤细胞的免疫原性和／或免疫系统的功能。它克服了以往细胞因子注射疗 法需反复、多次、大剂量所带来的副作用及多次注射所致的耐药性［2］等缺点，同 时也取得了细胞因子注射疗法所不具备的治疗效果，所以近年来倍受人们的关注。     

核医学与基因治疗

将基因治疗与核医学结合产生的基因表达显像,基因诱导受体显像,基因靶向性放射性核素治疗等,不仅主基因治疗开拓了核医学的研究领域,也为肿瘤的诊断和治疗提供新的思路和方法,虽然基因治疗中还存在着不少问题,相信随着分子生物学的不断发展,核医学在基因治疗中的作用将得到进一步的体现。     

Radioimmunotherapy of B-cell non-Hodgkin's lymphoma: from clinical trials to clinical practice.

Radioimmunotherapy (RIT) is a new treatment modality for B-cell non-Hodgkin's lymphoma (NHL). Recent clinical trials have clearly established its efficacy in NHL patients refractory to standard chemotherapy or immunotherapy with the widely used unconjugated rituximab monoclonal antibody (mAb). The Food and Drug Administration has approved (90)Y-ibritumomab tiuxetan anti-B-cell NHL mAb as the first commercially available radiolabeled antibody for cancer therapy. This comes only a few years after the introduction of rituximab into clinical practice as the first unconjugated antibody for cancer treatment, underscoring the success of both immunotherapy and RIT in the treatment of NHL. With the approval of (90)Y-ibritumomab tiuxetan, and based on the results of numerous clinical trials with radiolabeled anti-B-cell NHL mAbs, RIT promises to become integral to nuclear medicine practice. In this article, the basic concepts of RIT are reviewed with important milestones in its development for B-cell NHL treatment and particular emphasis on phase II and III clinical trials establishing its efficacy in clearly defined patient populations. Finally, the prospects for the expected widespread clinical use of RIT in the management of B-cell NHL, alone or in combination with other more established therapies, are discussed. This article provides both investigative and clinical nuclear medicine physicians with a better understanding of RIT capabilities and limitations in B-cell NHL and their role as consultants in the care of NHL patients.     

树突状细胞联合细胞因子介导杀伤细胞免疫治疗肾癌临床研究

目的:探讨以树突状细胞(dendritic cells,DC)联合细胞因子介导杀伤细胞(cytokine induced killer,CIK)为基础的免疫途径治疗恶性实体肿瘤的临床疗效.方法:将60例临床确诊的肾透明细胞癌患者随机分为两组:治疗组给予手术联合细胞免疫治疗,对照组给予手术及细胞因子治疗.采集肿瘤患者的外周血单核细胞,体外诱导培养成熟DC及CIK细胞,最后再回输给患者.观察疗效和治疗前后细胞免疫指标变化(CD3+、CD4+、CD8+、CD4+/CD8+、NK细胞)、外周血象、肝肾功能变化(白细胞、转氨酶、尿素氮、肌酐)及不良反应.结果:治疗组有效率43.33%,对照组有效率26.67%,治疗组与对照组相比,差异有统计学意义(P＜0.05).治疗组CD3+、CD4+、CD4+/CD8+免疫学指标治疗前后比较,差异有统计学意义(P值分别为0.010,0.026,0.021),治疗组细胞免疫学指标(CD3+、CD4+、CD4+/CD8+)在治疗前后变化与对照组相比,结果差异有统计学意义(P值分别为0.001,0.023,0.012).两组患者外周血象及肝肾功能检测无异常,免疫治疗过程中未出现明显的毒副作用.结论:以DC、CIK细胞为基础的细胞免疫治疗可以明显改善肾癌术后患者临床疗效,提高外周血淋巴细胞亚群及NK细胞水平,临床应用无明显不良反应,是肾癌术后重要的辅助治疗手段.     

肝癌根治性切除术后免疫治疗联合肝动脉化疗栓塞的临床研究

目的 研究肝癌根治性切除术后免疫治疗联合肝动脉化疗栓塞的价值。材料与方法 肝癌根治性切除者80例,随机分为两组。肝癌根治性切除术后免疫治疗联合肝动脉化疗栓塞40例为观察组;肝癌根治性切除术后单纯免疫治疗40例为对照组。对两组病例1年、2年的肝内复发率和生存率分别作x^2检验,进行对照分析。结果 观察组１年、２年的肝内复发率分别为１２．５％（5／40）、30．0％（12／40）,较对照组32．5％（13／40）、52．5％（21／40）降低（x^2值分别为4．59、4．18,P值均＜0．05）;观察组1年、2年的生存率分别为85．0％（34／40）、70．0％（28／40）,较对照组65．0％（26／40）、47．5％（19／40）提高（x^2值分别为4．27、4．18,P值均＜0．05）。结论 肝癌根治性切除术后免疫治疗联合肝动脉化疗栓塞是控制肝内复发率,提高患者生存率的有价值的治疗方法。     

肿瘤免疫治疗疗效评价标准—iRECIST解读

近年来,肿瘤免疫治疗迅猛发展,而现有世界卫生组织标准或实体瘤疗效评价标准(response evaluation criteria in solid tumor,RECIST)无法对免疫治疗疗效进行准确的解读和确切的评估,尤其是反映肿瘤缓解或进展的关键问题—肿瘤负荷的变化。基于此,RECIST工作组结合临床肿瘤免疫治疗实践改良的实体肿瘤疗效评价标准（RECIST版本1.1）制定了一个新的肿瘤免疫治疗疗效评价标准—实体瘤免疫治疗疗效评价标准（immune response evaluation criteria in solid tumor,iRECIST）,并在2017年第18期的The Lancet Oncology上发表。该标准详细定义了实体瘤测量及肿瘤大小评价的标准方法,以期在后续肿瘤免疫治疗临床试验中得以验证。作者对这一新的标准作一介绍。     

甲状腺癌的基因治疗

甲状腺癌的基因治疗包括免疫基因疗法,自杀基因疗法,抑癌基因疗法,NIS基因介导的131I治疗,反义基因治疗等,具有广阔的前景,但应用于临床还有许多的问题需要解决。     

PET imaging of cancer immunotherapy.

Immune system activation can be elicited in viral infections, active immunization, or cancer immunotherapy, leading to the final common phenotype of increased glycolytic use by immune cells and subsequent detection by 18F-FDG PET. Because 18F-FDG is also used in baseline staging PET/CT scans and in tumor response assessment, physicians are faced with a unique challenge when evaluating tumor response in patients receiving cancer immunotherapy. The burgeoning field of cancer immunotherapy and the paucity of PET probes that can reliably differentiate activated immune cells from metabolically active cancer cells underscore the pressing need to identify and develop additional molecular imaging strategies. In an effort to address this concern, investigators have taken several molecular imaging approaches for cancer immunotherapy. Direct ex vivo labeling of T lymphocytes with radioactive probes before reinfusion represents the earliest attempts but has proven to be clinically limited because of significant PET probe dilution from proliferation of activated immune cells. Another approach is the indirect in vivo labeling of immune cells via PET reporter gene expression and involves the ex vivo genetic engineering of T lymphocytes with a reporter gene, reinfusion into the host, and the subsequent use of a PET probe specific for the reporter gene. The most recent approach involves the direct in vivo labeling of immune cells by targeting endogenous immune cell biochemical pathways that are differentially expressed during activation. In conclusion, these novel PET-based imaging approaches have demonstrated promise toward the goal of in vivo, noninvasive immune monitoring strategies for evaluating cancer immunotherapy.     

放疗联合免疫抗肿瘤治疗策略的研究进展

随着人类对肿瘤的认识不断深入,越来越多的证据表明肿瘤的发生发展与机体的免疫功能密切相关,寻找有效的手段提高机体抗肿瘤免疫已成为肿瘤免疫学研究的热点。放射治疗虽是传统肿瘤治疗方式,但近来研究发现其可使“冷肿瘤”转变为“热肿瘤”,改善肿瘤免疫抑制微环境,提高肿瘤免疫原性,激活细胞免疫应答,从而在抗肿瘤免疫调节中发挥重要作用。然而,单独放疗产生的“远隔效应”在临床中并不常见,需要免疫治疗作为“推动者”增强放疗诱导的免疫效应。本文对放疗联合免疫抗肿瘤相关基础理论和临床实践进行综述,期望能为临床相关治疗策略提供参考。     

Clinical characteristics of patient selection and imaging predictors of outcome in solid tumors treated with checkpoint-inhibitors

The rapidly evolving knowledge on tumor immunology and the continuous implementation of immunotherapy in cancer have recently led to the FDA and EMA approval of several checkpoint inhibitors as immunotherapic agents in clinical practice. Anti-CTLA-4, anti-PD-1, and anti-PDL-1 antibodies are becoming standard of care in advanced melanoma, as well as in relapsed or metastatic lung and kidney cancer, demonstrating higher and longer response compared to standard chemotherapy. These encouraging results have fostered the evaluation of these antibodies either alone or in combination with other therapies in several dozen clinical trials for the treatment of multiple tumor types. However, not all patients respond to immune checkpoint inhibitors, hence, specific biomarkers are necessary to guide and monitor therapy. The utility of PD-L1 expression as a biomarker has varied in different clinical trials, but, to date, no consensus has been reached on whether PD-L1 expression is an ideal marker for response and patient selection; approximately 20–25% of patients will respond to immunotherapy with checkpoint inhibitors despite a negative PD-L1 staining. On the other hand, major issues concern the evaluation of objective response in patients treated with immunotherapy. Pure morphological criteria as commonly used in solid tumors (i.e. RECIST) are not sufficient because change in size is not an early and reliable marker of tumor response to biological therapies. Thus, the scientific community has required a continuous adaptation of immune-related response criteria (irRC) to overcome the problem. In this context, metabolic information and antibody-based imaging with positron emission tomography (PET) have been investigated, providing a powerful approach for an optimal stratification of patients at staging and during the evaluation of the response to therapy. In the present review we provide an overview on the clinical characteristics of patient selection when using imaging predictors of outcome in solid tumors treated with checkpoint-inhibitors.     

CML的基因沉默与过继免疫治疗的研究进展

慢性粒细胞白血病是一种造血干细胞的恶性克隆增殖性疾病,以分子生物学、免疫学、细胞生物学为基础的治疗手段成为新的研究方向。 siRNA介导的基因沉默通过降解靶标mRNA,miRNA介导的基因沉默通过使靶mRNA失去稳定性以减少蛋白质的生成,从而提高靶向治疗药物的治疗效果。过继免疫治疗是通过将CIK、NK等免疫活性细胞注入肿瘤宿主体内,提高机体免疫力,与靶向治疗药物协同提升治疗效果。其理论基础、分子机制、临床疗效等还需进一步深入研究。     

PDT for Gastric Cancer — the view from China

The incidence rate and mortality of gastric cancer remain elevated. Traditionally, surgical treatment (including endoscopic surgery and traditional surgery), chemotherapy, targeted therapy, and immunotherapy were used for the treatment of gastric cancer. Although the emergence of targeted therapy and immunotherapy can effectively prolong the survival of some patients with gastric cancer and improve the quality of life of patients after chemotherapy or surgery, the overall survival rate of gastric cancer has not been significantly improved. Photodynamic therapy is a local photochemical therapy with the advantages of high safety, few adverse reactions, and repeatability, although it may cause some toxic reactions. There are some differences between East and West in the treatment of gastric cancer with PDT, and most earlier studies concentrated on using PDT alone. However, some studies have indicated that PDT may enhance the efficacy of chemotherapy and other medications. This paper summarizes the study on the use of PDT and its combination therapy in gastric cancer, which is anticipated to offer novel thoughts for the treatment of gastric cancer.