肿瘤干细胞的研究现状

肿瘤干细胞是近年来肿瘤研究的一个新热点,它具有强大的自我更新和致瘤能力,以及细胞分化潜能。本文介绍了造血系统恶性肿瘤干细胞,乳腺癌干细胞,类神经肿瘤干细胞等其他肿瘤干细胞的研究现状,并对其耐药机制进行阐述。     

基于靶向纳米递药系统用于胰腺癌化疗中的研究现状

胰腺癌是一种恶性程度较高、诊断和治疗均较困难的消化道系统肿瘤。胰腺癌的传统化疗方案靶向性不高,治疗效率低,存在一系列的药物不良反应。近年来纳米靶向递药系统迅猛发展,为胰腺癌的治疗提供了许多的新思路。本文综述了近年来基于靶向纳米递药系统用于胰腺癌化疗的研究进展,从被动靶向、物理化学靶向、主动靶向和化疗药物的联合运载四个方面中的应用进行介绍,以期为胰腺癌的临床治疗提供新的思路和方法。     

成球培养法富集胰腺癌肿瘤干细胞的研究

目的 研究成球培养法培养胰腺癌肿瘤干细胞的可行性。方法 通过细胞成球培养体系富集胰腺癌肿瘤干细胞并进行培养,流式细胞术检测分析干细胞的表型特征。结果 光镜下,成球培养细胞形态发生明显变化,细胞由贴壁时的多边形变成圆形,并形成肿瘤细胞微球。流式细胞仪检测发现,与普通细胞培养相比,成球培养体系富集的胰腺癌肿瘤干细胞干性相关基因CD24、CD44共表达水平明显升高。结论 利用成球培养法能够富集得到CD24、CD44高表达的胰腺癌肿瘤干细胞。     

给药系统进展概述(下)

目前药物治疗全身性疾病是通过各种途径给药,达到一定的血药浓度分布于全身而产生治疗作用,这种治疗方法最大的缺陷是缺乏选择性。如某些疾病只局限于某个部位或器官,则到达的药物仅一小部分,大部分药物未发挥作用,某些强烈的药物往往在起治疗作用的同时产生毒副作用,严重地影响药物的治疗价值。     

口服结肠靶向给药系统的研究现状

通过查阅献资料，综述了近几年来国内外口服结肠靶向药给系统的研究情况，介绍了口服结肠靶向给药的概念及其优点和结肠靶向给药系统的几种类型：pH依赖型，时滞释药型，菌群触发型及其使用的材料。     

沉默Oct4和Nanog基因抑制胰腺癌干细胞的生物学特征

目的探讨特异短发夹RNA(shRNA)沉默胰腺癌PANC-1肿瘤干细胞(PCSCs)生物学特征的变化及其机制。方法从PANC-1细胞株中分离出CD44+CD24+上皮特异性抗原(ESA)+PCSCs,检测Oct4和Nanog蛋白表达。用慢病毒载体介导的shRNA沉默PCSCs中Oct4和Nanog表达,用荧光定量RT-PCR和Western blot检测干扰效率。通过单克隆形成实验、Transwell小室模型、细胞计数试剂盒8(CCK8)检测Oct4和Nanog对PCSCs增殖、迁移、侵袭和药物敏感性的影响。NOD/SCID小鼠致瘤实验观察Oct4和Nanog对PCSCs致瘤性的影响。结果 PANC-1细胞株中PCSCs占0.1%-0.8%,Oct4和Nanog在PCSCs中呈高表达(P<0.05);慢病毒载体介导的shRNA降低PCSCs中Oct4和Nanog的表达(P<0.05)。沉默Oct4、Nanog后,PCSCs的单克隆形成、增殖、迁移、侵袭能力下降,药物敏感性增强并诱导凋亡(P<0.05)。致瘤实验表明,沉默Oct4和Nanog后,PCSCs致瘤能力下降(P<0.05)。结论 Oct4和Nanog在PCSCs中高表达,慢病毒介导的shRNA可沉默PCSCs中Oct4、Nanog的表达。沉默PCSCs中Oct4和Nanog的表达可抑制PCSCs相关生物学特征,增强其药物敏感性并诱导细胞凋亡。     

结肠靶向给药系统研究概况

本文对结肠靶向给药系统的特点、当前制剂学手段进行介绍与分析，认为结肠靶向给药对便秘、结肠炎、大肠癌等肠道疾病的治疗以及蛋白多肽药物的口服给药都具有重要意义，是一个极具前景的新药研究领域。     

肝癌靶向治疗的进展

随着分子靶向药物的研发和临床应用,肿瘤的分子靶向治疗已成为肿瘤治疗领域研究的热点.现有的研究结果已表明,肿瘤分子靶向治疗具有较好的安全性和有效性,已在临床中取得较好的疗效.     

胰腺癌药物治疗进展分析

吉西他滨是目前晚期胰腺癌化疗的一线药物,未发现其他化疗药物与吉西他滨联合治疗胰腺癌能显著延长患者生存期。因此,针对胰腺癌生物学特性进行治疗是改善预后的关键。本文阐述了胰腺癌治疗中吉西他滨与靶向药物联合应用的情况。     

Nanocarrier-mediated drugs targeting cancer stem cells: an emerging delivery approach

Introduction: Cancer stem cells (CSCs) play an important role in the development of drug resistance, metastasis and recurrence. Current conventional therapies do not commonly target CSCs. Nanocarrier-based delivery systems targeting cancer cells have entered a new era of treatment, where specific targeting to CSCs may offer superior outcomes to efficient cancer therapies.

Areas covered: This review discusses the involvement of CSCs in tumor progression and relevant mechanisms associated with CSCs resistance to conventional chemo- and radio-therapies. It highlights CSCs-targeted strategies that are either under evaluation or could be explored in the near future, with a focus on various nanocarrier-based delivery systems of drugs and nucleic acids to CSCs. Novel nanocarriers targeting CSCs are presented in a cancer-specific way to provide a current perspective on anti-CSCs therapeutics.

Expert opinion: The field of CSCs-targeted therapeutics is still emerging with a few small molecules and macromolecules currently proving efficacy in clinical trials. However considering the complexities of CSCs and existing delivery difficulties in conventional anticancer therapies, CSC-specific delivery systems would face tremendous technical and clinical challenges. Nanocarrier-based approaches have demonstrated significant potential in specific drug delivery and targeting; their success in CSCs-targeted drug delivery would not only significantly enhance anticancer treatment but also address current difficulties associated with cancer resistance, metastasis and recurrence.     

Potential use of aptamers for diagnosis and treatment of pancreatic cancer

Abstract

Pancreatic cancer (PC) is highly malignant with a low 5-year survival rate. PC currently does not have good early diagnostic markers and responses poorly to chemotherapeutic drugs. The search for better biomarkers and developing more effective chemotherapy are important ways to improve the healthcare of PC patients. Aptamers are single-stranded nucleic acids with high binding affinity and specificity to target molecules. Many aptamers against different forms of cancer including PC have been selected for both diagnostic and therapeutic use. Aptamers can work as ligands to distinguish tumour cells from normal cells. Using cells as selection targets, the obtained aptamers have been used to discover new cancer biomarkers after identification of the binding target. Aptamers have been shown to have antagonists effect on cancer cell proliferation, apoptosis, and metastasis. In addition, aptamers have been used as carriers to deliver therapeutic agents to selectively kill PC cells. This review summarises the potential use of aptamers in the diagnosis and treatment of PC.     

Overcoming drug resistance in pancreatic cancer

Introduction: Pancreatic cancer has the worst survival rate of all cancers. The current standard care for metastatic pancreatic cancer is gemcitabine, however, the success of this treatment is poor and overall survival has not improved for decades. Drug resistance (both intrinsic and acquired) is thought to be a major reason for the limited benefit of most pancreatic cancer therapies.

Areas covered: Previous studies have indicated various mechanisms of drug resistance in pancreatic cancer, including changes in individual genes or signaling pathways, the influence of the tumor microenvironment, and the presence of highly resistant stem cells. This review summarizes recent advances in the mechanisms of drug resistance in pancreatic cancer and potential strategies to overcome this.

Expert opinion: Increasing drug delivery efficiency and decreasing drug resistance is the current aim in pancreatic cancer treatment, and will also benefit the treatment of other cancers. Understanding the molecular and cellular basis of drug resistance in pancreatic cancer will lead to the development of novel therapeutic strategies with the potential to sensitize pancreatic cancer to chemotherapy, and to increase the efficacy of current treatments in a wide variety of human cancers.     

Cancer stem cell-targeted therapeutics and delivery strategies

Introduction: Cancer initiating or stem cells (CSCs) are a small population of cells in the tumor mass, which have been reported to be present in different types of cancers. CSCs usually reside within the tumor and are responsible for reoccurrence of cancer. The imprecise, inaccessible nature and increased efflux of conventional therapeutic drugs make these cells resistant to drugs. We discuss the specific markers for identification of these cells, role of CSCs in chemotherapy resistance and use of different therapeutic means to target them, including elucidation of specific cell markers, exploitation of different signaling pathways and use of nanotechnology.

Area covered: This review covers cancer stem cell signaling which are used by these cells to maintain their quiescence, stemness and resistant phenotype, distinct cell surface markers, contribution of these cells in drug resistance, inevitability to cure cancer and use of nanotechnology to overcome this hurdle.

Expert opinion: Cancer stem cells are the main culprit of our failure to cure cancer. In order to cure cancer along with other cells types in cancer, cancer stem cells need to be targeted in the tumor bed. Nanotechnology solutions can facilitate clinical translation of the therapeutics along with other emerging technologies to cure cancer.     

肿瘤干细胞耐药机制研究进展

肿瘤是一种干细胞疾病,治疗肿瘤面临的主要挑战之一是肿瘤对传统治疗产生了耐药性,研究证明耐药性的产生与肿瘤干细胞(cancer stem cells,CSCs)的生物学特性密切相关。鉴定各种肿瘤中的CSCs以及维持其特性所必需的微环境和生物学进程对治疗肿瘤复发至关重要。CSCs周围局部微环境(niche)的改变能影响其生物学行为,而多种与发育相关的信号通路的激活,DNA修复能力的增强以及ABC转运蛋白介导的药物外排等是导致临床耐药的主要原因。该文就近年来CSCs与耐药的相关研究进展作一综述。     

肿瘤干细胞的耐药性及其治疗策略

随着对肿瘤研究的不断深入,以及对干细胞了解的日益加深,越来越多的证据表明肿瘤中某些细胞具有干细胞特性,由此提出了肿瘤干细胞学说。这一学说,不仅认为肿瘤的生长、转移与肿瘤干细胞的关系密切,而且传统的化疗方法不能根治肿瘤的原因可能也与肿瘤干细胞耐药有关。已有研究表明, ABC转运体能够保护肿瘤干细胞免受药物的毒性作用,因此更深入的理解肿瘤干细胞耐药机制对我们找到行之有效的肿瘤治疗方法以及新的治疗靶点有十分重要的意义。     

胰腺癌的流行病学与诊治现状分析

胰腺癌恶性程度高,手术切除率低,预后极差,其早期症状表现不典型,所以早期诊断较难。我国胰腺癌的发病率呈逐年上升趋势,但目前国内在胰腺癌的诊治中尚存在许多不足,胰腺癌相关的基础研究不够深入。本文对胰腺癌的最新流行病学数据、诊治现状及存在的问题进行了分析,为当下国内胰腺癌的诊疗提供参考。     

Advances in stem cells,induced pluripotent stem cells,and engineered cells: delivery vehicles for anti-glioma therapy

Introduction: A limitation of small molecule inhibitors, nanoparticles (NPs) and therapeutic adenoviruses is their incomplete distribution within the entirety of solid tumors such as malignant gliomas. Currently, cell-based carriers are making their way into the clinical setting as they offer the potential to selectively deliver many types of therapies to cancer cells.

Areas covered: Here, we review the properties of stem cells, induced pluripotent stem cells and engineered cells that possess the tumor-tropic behavior necessary to serve as cell carriers. We also report on the different types of therapeutic agents that have been delivered to tumors by these cell carriers, including: i) therapeutic genes; ii) oncolytic viruses; iii) NPs; and iv) antibodies. The current challenges and future promises of cell-based drug delivery are also discussed.

Expert opinion: While the emergence of stem cell-mediated therapy has resulted in promising preclinical results and a human clinical trial utilizing this approach is currently underway, there is still a need to optimize these delivery platforms. By improving the loading of therapeutic agents into stem cells and enhancing their migratory ability and persistence, significant improvements in targeted cancer therapy may be achieved.     

雷公藤甲素治疗胰腺癌的研究进展

胰腺癌是一种消化道常见恶性肿瘤之一,预后差,诊断期较晚。雷公藤甲素是雷公藤中有效成分之一,具有显著的药理活性。雷公藤甲素可通过抑制细胞周期和增殖、诱导细胞凋亡、抑制细胞迁移和侵袭、调节肿瘤血管生成、协同其他药物抗耐药、抑制热休克蛋白相关基因、诱导自噬等多种途径治疗胰腺癌。总结了雷公藤甲素治疗胰腺癌的药理作用及其作用机制的研究进展,为雷公藤甲素成为胰腺癌治疗的候选药物提供依据。