SELDI-TOF-MS技术在临床肿瘤蛋白质组学研究中的应用

恶性肿瘤严重地威胁着人类的健康和生命。多年来,人类一直在为治疗肿瘤而奋斗。众所周知,恶性肿瘤的早期发现、早期诊断、早期治疗是提高大多数恶性肿瘤患者治疗效果的关键。同时,肿瘤的早期发现也能减少肿瘤转移和播散的机会。癌症发现、确诊得越早,治疗成功的可能性就越大,患者的生存率也就会越高。目前,SELDI-TOF-MS技术在临床肿瘤蛋白质组学研究中已经得到了普遍应用,研究的范围几乎覆盖所有的常见肿瘤,为临床肿瘤的蛋白质组学研究奠定了良好的基础。以下概要介绍SELDI—TOF-MS技术在部分肿瘤中的研究应用。     

肿瘤干细胞在肿瘤治疗中的研究进展

肿瘤干细胞(cancer stem cells,CSCs)学说的成熟发展和研究成为当前肿瘤治疗研究的热点之一,因其特殊的生物学特性在肿瘤防治中起重要作用。以CSCs为靶点为肿瘤治疗开辟了一条新思路。传统的治疗不能有效靶向CSC,开发针对CSC靶向治疗的新方法,将对肿瘤的耐药、复发、转移具有革新意义。     

蛋白质组学技术在神经系统疾病研究中的作用

双向凝胶电泳和质谱等方法都是蛋白质组学(Proteomics)技术的重要方法。应用蛋白质组学技术可以同时研究大量蛋白质的功能、组成,多样性及其动态变化。神经科学的许多问题可以借助于这个新的工具平台获得解决,因此,蛋白质组学的发展,将为神经疾病发病机制的深入研究,以及相关的药物开发提供一个崭新的发展机遇。     

蛋白质组学新技术及其在肿瘤标志物探索性研究中的应用

作为基因组研究的延伸,蛋白质组学已成为世界生命科学领域的一个极其活跃的部分,是功能基因组时代或后基因组时代的核心。近年来发展起来的几种蛋白质组学新技术克服了传统蛋白质组学技术的不足,有力推进了肿瘤标志物的探索性研究。尽管如此,我们仍应该强调对实验结果的验证,这一点在探索性研究中尤其重要,力求使结果更精确、可靠和有效。     

应用蛋白质组学筛选宫颈癌患者尿液中的肿瘤标志物

通过比较健康女性和宫颈癌患者的尿蛋白质组,发现并分析差异表达蛋白,从中筛选潜在的宫颈癌的标志物。研究对象由43名宫颈癌患者（CC）和47名健康女性（HW）组成。用超速离心法沉淀尿蛋白,再用一维凝胶电泳（SDS-PAGE）与液相色谱-质谱联用技术（LC-MS/MS）鉴定尿液中的蛋白质,蛋白质定量采用无标定量。比较患者尿蛋白质组、健康对照的尿蛋白质组和宫颈癌组织蛋白质组,有1910个蛋白质是患者和健康对照共有的尿蛋白,这其中有746个蛋白质也存在于宫颈癌组织蛋白质组。在这746个蛋白质中找到84个上调蛋白和82下调蛋白。通过生物信息学分析发现牛皮癣素（S100A7）和癌胚抗原相关细胞黏附分子8（CEACAM8）是宫颈癌尿液样本独有蛋白质。在验证组的70例样本中,双盲法测试S100A7、CEACAM8以及两者联合诊断宫颈癌的敏感性能达到73%、87%、93%。结果提示,宫颈癌患者的尿蛋白质组与健康女性的尿蛋白质组不同,并且S100A7和CEACAM8可以作为宫颈癌潜在的肿瘤标志物。     

植物蛋白质组学的研究进展

植物蛋白质组学的研究取得了重要进展。全面介绍了植物器官蛋白质组、植物组织蛋白质组及植物亚细胞蛋白质组的研究进展。     

果蝇蛋白质组学研究进展

蛋白质组学旨在阐明基因组所表达的真正执行生命活动的全部蛋白质的表达规律和生物功能。随着人类基因组学计划的逐渐成熟,分子水平的实验技术不断发展,蛋白质组学的研究被提高到了前所未有的高度。果蝇是生命科学领域最为常用的一种模式生物,长期的系统研究也使果蝇的基因组成为至今注释最好的基因组之一,为功能基因组研究奠定了基础。但由于技术的限制,迄今有关果蝇蛋白质组学研究的报道尚不多见。近年来果蝇蛋白质组学的研究主要包括表达谱、修饰谱、比较蛋白质组学和疾病模型蛋白质组等四个方向,为进一步开展人类疾病临床蛋白质组学研究奠定了基础。     

葡萄蛋白质组学研究进展

人类基因组计划的完成标志着生命科学已进入后基因组时代,蛋白质组学的研究被提升到了前所未有的高度,蛋白质组学旨在阐明基因组所表达的真正执行生命活动的全部蛋白质的表达规律和生物功能。伴随葡萄基因组测序工作的完成,有关葡萄蛋白质组学的研究迅速发展。对近年来蛋白质组学在葡萄上的研究进行了综述,内容主要包括:葡萄蛋白质样品的提取制备,葡萄果实发育和品质形成过程中蛋白质组的变化,葡萄果皮、细胞壁、质膜等特定组织材料的蛋白质组研究,及蛋白质组学在葡萄逆境胁迫、体细胞胚的发生等方面的研究,并对葡萄蛋白质组学的发展趋势进行了展望。     

蛋白质芯片在肿瘤血清标识物发现中的应用

蛋白质芯片是一种新型的高通量蛋白质组学技术,由于其具有高通量、微型化、可平行快速分析等优点,因此在肿瘤血清标识物发现研究方面具有广泛的应用前景。本文综述了蛋白质芯片的基本原理、类型及其在肿瘤血清标记物发现研究中的应用,将蛋白质芯片技术与传统的肿瘤标志物发现技术进行了比较,并对蛋白质芯片技术在肿瘤标识物发现研究上的进一步应用进行了展望。     

结核杆菌蛋白质组学研究进展

结核病是对人类威胁最大的传染病之一,尽管牛型结核分枝杆菌疫苗（BCG）和各种抗结核药物在全球范围内得到了广泛应用,但近年来,随着人口流动及密度的增高,结核杆菌多重耐药菌株及同人体免疫缺陷病毒（HIV）双重感染的出现,结核病已在发达国家和发展中国家呈再度肆虐态势。     

癌细胞分泌蛋白质组富集与鉴定策略研究进展

分泌蛋白质中包含细胞因子、生长因子和激素等具有重要功能的生物活性分子,广泛参与细胞信号传导,细胞增殖、分化和凋亡的调控等多项重要生命过程。因此,从分泌体系中发掘生物标志物和治疗靶标,是癌症蛋白质组研究的一个重要方向。传统的分泌蛋白质体系主要包括血浆、尿液、脑脊液和组织间隙液等,这些系统的一个主要特点是其所包含的蛋白质浓度范围跨度很大,对蛋白质组分离和鉴定提出巨大挑战。而收集肿瘤细胞在无血清体系中培养时所分泌的蛋白质,开展蛋白质组研究,则可以避开常规分泌系统中大量高丰度蛋白质的干扰,获得肿瘤特异性的细胞分泌蛋白谱。近年来,随着蛋白质组学技术的发展和质谱仪的进步,癌细胞分泌蛋白质组学的研究进展很快。我们系统回顾了癌细胞分泌蛋白质组富集方法和鉴定策略的发展,概括了癌细胞分泌蛋白质组研究现状和规模,为该领域的进一步研究奠定基础。     

硫酸软骨素在癌症治疗领域的研究进展

硫酸软骨素是一种硫酸化的糖胺聚糖,其在恶性肿瘤组织中的含量、结构、硫酸化位点等与正常组织存在显著差异,在癌症的迁移,侵袭,血管生成过程中发挥重要调控作用,在癌症的临床研究中具有很大潜力。该文对硫酸软骨素的生物合成进行归类分析,对近几年硫酸软骨素与肿瘤入侵和转移的相关临床研究以及分子机制研究做出综述,以期为开发硫酸软骨素潜在的临床价值和肿瘤治疗靶点研究提供理论依据,为恶性肿瘤的早期诊断和预后评估提供思路。     

Tumor interstitial fluid — A treasure trove of cancer biomarkers

Tumor interstitial fluid (TIF) is a proximal fluid that, in addition to the set of blood soluble phase-borne proteins, holds a subset of aberrantly externalized components, mainly proteins, released by tumor cells and tumor microenvironment through various mechanisms, which include classical secretion, non-classical secretion, secretion via exosomes and membrane protein shedding. Consequently, the interstitial aqueous phase of solid tumors is a highly promising resource for the discovery of molecules associated with pathological changes in tissues. Firstly, it allows one to delve deeper into the regulatory mechanisms and functions of secretion-related processes in tumor development. Secondly, the anomalous secretion of molecules that is innate to tumors and the tumor microenvironment, being associated with cancer progression, offers a valuable source for biomarker discovery and possible targets for therapeutic intervention. Here we provide an overview of the features of tumor-associated interstitial fluids, based on recent and updated information obtained mainly from our studies of breast cancer. Data from the study of interstitial fluids recovered from several other types of cancer are also discussed. This article is a part of a Special Issue entitled: The Updated Secretome.     

胰腺癌相关肿瘤标志物研究进展

胰腺癌起病隐匿,进展快,预后差,发病率约等于死亡率。胰腺癌死亡率高的原因有发病机制不明,缺乏有效的早期诊断和预后的肿瘤标志物,进展期相关治疗效果不理想。近年来在血清标志物、基因标志物、表观遗传学标志物等分子生物技术及生物信息学方面的发展为胰腺癌的诊断,尤其是早期诊断、评估预后和监测早期复发提供了新的途径。本文就近期胰腺癌相关肿瘤标志物的研究进展作一综述。     

多种血清肿瘤标志物联合检测对肺癌诊断的临床意义分析

目的:探讨CA125、CYFRA21-1、CEA、NSE、AFP联合检测对肺癌的诊、诊断的敏感度以及特异性。方法:对我院收治的确诊为肺癌的患者选取120例作为A组,同期选择肺部良性病变患者61例作为B组,以及50例健康体检患者作为C组,将三组研究对象分别进行CA125、CYFRA21-1、CEA、NSE、AFP的检测。结果:A组患者CA125、CYFRA21-1、CEA、NSE、AFP的血清中含量明显高于B组以及C组(P<0.05);五种标记物联合检测的敏感度明显高于单一标志物的敏感度(P<0.05),但其特异性有明显的降低(P<0.05)。结论:采用CA125、CYFRA21-1、CEA、NSE、AFP联合检测,对肺癌的早期诊断以及治疗预后有较好的指导作用。     

Analyzing the Secretome of Gut Microbiota as the Next Strategy For Early Detection of Colorectal Cancer

Dysbiosis of gut microbiome can contribute to inflammation, and subsequently initiation and progression of colorectal cancer (CRC). Throughout these stages, various proteins and metabolites are secreted to the external environment by microorganisms or the hosts themselves. Studying these proteins may help enhance our understanding of the host–microorganism relationship or they may even serve as useful biomarkers for CRC. However, secretomic studies of gut microbiome of CRC patients, until now, are scarcely performed. In this review article, the focus is on the roles of gut microbiome in CRC, the current findings on CRC secretome are highlighted, and the emerging challenges and strategies to drive forward this area of research are addressed.     

A Systematic Investigation of the Malignant Functions and Diagnostic Potential of the Cancer Secretome

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Clinical Relevance of Ion Channels for Diagnosis and Therapy of Cancer

Ion channels have a critical role in cell proliferation and it is well documented that channel blockers can inhibit the growth of cancer cells. The concept of ion channels as therapeutic targets or prognostic biomarkers attracts increasing interest, but the lack of potent and selective channel modulators has hampered a critical verification for many years. Today, the knowledge of human ion channel genes is almost complete and molecular correlates for many native currents have already been identified. This information triggered a wave of experimental results, identifying individual ion channels with relevance for specific cancer types. The current pattern of cancer-related ion channels is not arbitrary, but can be reduced to few members from each ion channel family. This review aims to provide an overview of the molecularly identified ion channels that might be relevant for the most common human cancer types. Possible applications of these candidates for a targeted cancer therapy or for clinical diagnosis are discussed.     

The immunosuppressive and pro-tumor functions of CCL18 at the tumor microenvironment

Chemokines are essential mediators of immune cell trafficking. In a tumor microenvironment context, chemotactic cytokines are known to regulate the migration, positioning and interaction of different cell subsets with both anti- and pro-tumor functions. Additionally, chemokines have critical roles regarding non-immune cells, highlighting their importance in tumor growth and progression.CCL18 is a primate-specific chemokine produced by macrophages and dendritic cells. This chemokine presents both constitutive and inducible expression. It is mainly associated with a tolerogenic response and involved in maintaining homeostasis of the immune system under physiological conditions. Recently, CCL18 has been noticed as an important component of the complex chemokine system involved in the biology of tumors. This chemokine induces T regulatory cell differentiation and recruitment to the tumor milieu, with subsequent induction of a pro-tumor (M2-like) macrophage phenotype. CCL18 is also directly involved in cancer cell-invasion, migration, epithelial-to-mesenchymal transition and angiogenesis stimulation, pinpointing an important role in the promotion of cancer progression. Interestingly, this chemokine is highly expressed in tumor tissues, particularly at the invasive front of more advanced stages (e.g. colorectal cancer), and high levels are detected in the serum of patients, correlating with poor prognosis.Despite the promising role of CCL18 as a biomarker and/or therapeutic target to hamper disease progression, its pleiotropic functions in a context of cancer are still poorly explored. The scarce knowledge concerning the receptors for this chemokine, together with the insufficient insight on the downstream signaling pathways, have impaired the selection of this molecule as an immediate target for translational research.In this Review, we will discuss recent findings concerning the role of CCL18 in cancer, integrate recently disclosed molecular mechanisms and compile data from current clinical studies.     

Evaluation of Oxidative Stress, Antioxidant Status and Serum Vitamin C Levels in Cancer Patients

Taking into account the importance role of lipid peroxidation and antioxidants in the prevention and incidence of cancer, the present study was carried out to determine oxidative stress, serum total antioxidant (TAS), and vitamin C levels in cancer patients. Malondialdehyde(MDA), total antioxidant status, and vitamin C levels of 57cancer patients aged 19–80 years and 22 healthy subjects (control group) aged 22–76 years were evaluated. Serum concentrations of MDA as thiobarbitaric acid complexes were measured by fluorometry method, the serum TAS by using commercial test kits from Randox Laboratories, and vitamin C by using spectrocolorimetric method. The mean serum MDA concentrations of all cancer groups except lung cancer were significantly higher than control group (P < 0.004). The mean total antioxidant status was insignificantly higher than control group. The mean serum vitamin C level was significantly lower in patients as compared to the healthy subjects (PV < 0.0001). In conclusion, an alteration in the lipid peroxidation with concomitant changes in antioxidant defense system in cancer patients may be due to excessive oxidative stress. Serum low levels of vitamin C in the different type of cancer patients in spite of adequate daily intake may be due to increased utilization to scavenge lipid peroxides as well as their sequestration by tumor cells.