血中游离DNA与肿瘤

血中游离DNA指血中游离于细胞之外的一类DNA,简称循环核酸,于1947年由Mandel和Metais发现。肿瘤患者外周血DNA水平高于正常人且血中游离DNA具有肿瘤细胞DNA的特征,如肿瘤相关基因的突变、微卫星改变、甲基化异常和线粒体DNA突变等。随着肿瘤分子生物学的深入研究,血中游离DNA定性定量分析已开始应用于肿瘤的早期诊断、个体化治疗和预后判断等。血中游离DNA结合各类分子生物学检测技术,有望成为具有一定敏感性及高特异性的临床诊断方法。此外,血中游离DNA还有可能成为非细胞形式的肿瘤转移的新途径。     

Circulating miR-155 expression in plasma: a potential biomarker for early diagnosis of esophageal cancer in humans

MicroRNAs (miRNAs) are postulated to play important roles in oncogenesis. Recently, extracellular miRNAs were detected in plasma or serum of diseased subjects. However, the role of circulating miRNAs in plasma/serum remains to be elucidated. In this study, the relative expressions of miR-155, miR-183, and miR-20a in esophageal tissue were found to be significantly associated with increased risk for esophageal cancer. The relative expressions of circulating miR-155 and miR-183 were significantly reduced in cancer patients. Circulating miR-155 showed significantly higher risk for esophageal cancer when adjusted by smoking status and alcohol use. Circulating miR-155 was found to have significant diagnostic value for esophageal cancer as evidenced by a receiver operating characteristic curve area of 66%. However, Pearson analysis showed no statistical correlation in the relative miRNAs expression between plasma and esophageal tissues, which suggested different origins of circulating miRNAs distinct from tumor cell miRNAs. In conclusion, results suggest that circulating miR-155 in plasma may serve as a reliable, novel, noninvasive biomarker for early diagnosis and detection of esophageal cancer.     

血清胸苷激酶1检测对肺癌患者诊断与预后评估的意义

目的探讨血清胸苷激酶1(TK1)检测对肺癌患者诊断与预后评估的意义。方法应用免疫印迹-增强化学发光法检测63例肺癌患者(A组)和14例健康体检者(B组)血清TK1水平。24例术后获随访6-18个月。其中,无肿瘤复发15例(无复发组),肿瘤复发9例(复发组);随访期同时检测了其他相关肿瘤标记物。结果 A组血清TK1水平明显高于B组[(2.37±3.74)pmol/Lvs.(0.32±0.42)pmol/L](P<0.01)。A组手术治疗后血清TK1水平显著降低(P<0.05)。复发组血清TK1均较术前升高;无复发组中1例血清TK1升高,其余14例均较术前降低。TK1与其他肿瘤标志物联合检测提高了预后评估的准确性。结论血清TK1水平升高对肺癌有辅助诊断价值,连续跟踪监测有利于肺癌治疗效果和预后的判断。     

Clinical significance of detecting serum thvmidine kinase 1 in diagnosis and prognosis evaluation of lung cancer

目的 探讨血清胸苷激酶1(TK1)检测对肺癌患者诊断与预后评估的意义.方法 应用免疫印迹-增强化学发光法检测63例肺癌患者(A组)和14例健康体检者(B组)血清TK1水平.24例术后获随访6-18个月.其中,无肿瘤复发15例(无复发组),肿瘤复发9例(复发组);随访期同时检测了其他相关肿瘤标记物.结果 A组血清TK1水平明显高于B组[(2.37±3.74) pmol/Lvs.(0.32±0.42) pmol/L](P＜0.01).A组手术治疗后血清TK1水平显著降低(P＜0.05).复发组血清TK1均较术前升高;无复发组中1例血清TK1升高,其余14例均较术前降低.TK1与其他肿瘤标志物联合检测提高了预后评估的准确性.结论 血清TK1水平升高对肺癌有辅助诊断价值,连续跟踪监测有利于肺癌治疗效果和预后的判断.     

血清miR-25与胃癌病理诊断和预后的相关性研究

目的研究血清miR-25水平与胃癌(GC)患者的临床病理特征、诊断和预后之间的关系。方法对184例GC患者,56例胃炎患者和78名健康对照者的血清样本进行实时定量聚合酶链反应(RT-qPCR),探讨miR-25水平与GC临床病理特征(包括诊断和预后)的关系。结果与胃炎患者和健康人员相比,GC患者血清miR-25水平显著上调;以cutoff值0.042为标准,miR-25对GC患者的诊断敏感性为69.4%,特异性为80.4%;高血清miR-25水平与GC浸润深度和淋巴结转移相关,miR-25水平升高是患者预后不良的表现。结论血清miR-25水平是胃癌诊断和判断预后的一项可靠指标。     

MicroRNA在肺癌早期诊断、预后判断和治疗中的作用

肺癌是目前世界范围内引起死亡人数最多的肿瘤。在蛋白和基因水平上,肺癌发生的分子网络已经部分得到阐明,基于肺癌发生分子网络的基因治疗在过去10年取得了一定的进展,但是肺癌的5年死亡率并没有得到明显的改善(80%～85%)。MicroRNA这一内源性、非编码的短RNA的发现为提高肺癌患者的存活率带来了新的希望。肺癌中microRNA的表达模式不但与肺癌的诊断、分期、进展、预后相关,也为肺癌的基因治疗以及其他常规化疗药物的开发提供了新的研究方向和方法。     

The application of locked nucleic acids in the treatment of cancer

Locked nucleic acid (LNA) is a novel high-affinity and biologically stable RNA analog in which the normally flexible ribose sugar ring is fixed in a rigid conformation through a methylene 2'-O, 4'-C linkage. This fixed conformation brings substantial advantages to the design of effective RNA binding drugs, and enables single-stranded LNA oligonucleotides, termed 'RNA antagonists', to have superior efficacies in vivo in downregulating target mRNA when compared to oligonucleotides based on other chemistries or to published short interfering RNA. The features that allow LNA to be a valuable drug platform include unprecedented RNA binding affinity, excellent specificity, resistance to enzymatic degradation, safety, and ease of manufacture. Santaris Pharma A/S holds worldwide rights to the application of LNA in therapeutics, and is engaged in the clinical development of a series of drug candidates against cancer and metabolic diseases. SPC-2996, the company's most advanced product in development, entered an international, open-label, multicenter, phase I/II clinical trial in patients with severe chronic lymphocytic leukemia in May 2005. This trial is the first clinical evaluation of LNA chemistry. Two other LNA compounds have completed good laboratory practice safety studies with satisfactory outcome, and are likely to commence undergoing clinical development by 2007.     

血清铁蛋白在风湿性疾病诊断及治疗中的价值

目的：探讨血清铁蛋白（SFe）在判断风湿性疾病活动和转归中的价值。方法：收集2008年7月至2009年2月皖南医学院弋矶山医院风湿免疫科住院的156例风湿性疾病患者临床资料,并以同期健康志愿者20例作为正常对照。比较各疾病组与正常对照组之间SFe水平。各疾病组SFe水平与血沉（ESR）、C反应蛋白（CRP）、抗环瓜氨酸肽抗体（CCP-Ab）、补体C3等临床指标进行相关性分析。结果：成人still病（AOSD）组（n=18）平均SFe水平为（1707±387）ng/mL,（143±100）ng/mL,n=20,P=0.000;类风湿关节炎（RA）组（n=42）平均SFe为（299±228）ng/mL,均显著高于正常对照组（P=0.028）;系统性红斑狼疮（SLE）组（n=30）平均SFe为（295±326）ng/mL,与正常对照组之间无统计学差异（P=0.050）。SLE活动指数（SLEdiseaseactivityindex,SLEDAI）积分〉10分组（n=12）平均SFe为（338±225）ng/mL,显著高于SLEDAI积分≤10分组（n=18）平均SFe（158±123）ng/mL,t=2.534,P=0.042。相关分析表明,RA组SFe与CCP-Ab水平有显著相关性（r=0.531,P=0.004）,与其它临床指标无显著相关性。结论：SFe对诊断AOSD有重要意义,与AOSD及RA病情活动有关,当SLE高度活动时,其SFe水平也显著升高。     

Cancer regulator microRNA: potential relevance in diagnosis, prognosis and treatment of cancer

MicroRNAs (miRNAs) are small (typically 22 nucleotides) non-coding, endogenous, single-stranded RNAs. MiRNA genes are evolutionarily conserved and are located within the introns or exons of protein-coding genes, as well as in intergenic areas. Before the discovery of miRNAs, it had been known that a large part of the genome is not translated into proteins. This so called "junk" DNA was thought to be evolution debris with no function. Recently, the explosive research in this area has established miRNAs as powerful regulators of gene expression. While only about 1,424 human miRNA sequences have been identified so far, genomic computational analysis indicates that as many as 50,000 miRNAs may exist in the human genome, and each may have multiple targets based on similar sequences in the 3'-UTR of mRNA. MiRNAs have been implicated in different areas such as the immune response, neural development, DNA repair, apoptosis, oxidative stress response and others and it is impressive the list of diseases which have recently been found to be associated with abnormal miRNA expression. Here, we focus our attention on the importance of cancer regulator miRNAs. They are divided into oncomiRs and anti-oncomiRs that negatively regulate tumor suppressor genes and oncogenes, respectively. Importantly, the association of miRNAs with cancer has prompted additional functional classification of these short RNAs and their potential relevance in cancer diagnosis, prognosis and treatment.     

Evidence for extensive non-endocytotic translocation of peptide nucleic acids across mammalian plasma membranes

The ability of peptide nucleic acids (PNA) to enter and to cross filter-grown MDCK, HEK and CHO cells was studied by means of a protocol based on capillary electrophoresis combined with laser-induced fluorescence detection. The used approach avoided possible errors encountered in protocols based on confocal laserscanning microscopy and FACS analysis. In contradiction to the commonly anticipated unability of PNA to cross biomembranes, extensive translocation of unmodified PNA into and across the investigated cell types was found. The transport mode comprised a variety of energy dependent and -independent as well as temperature sensitive mechanisms being probably destined to natural substrates and hijacked by PNA. The presented results suggest active as well as passive export mechanisms rather than poor penetration into cells to be responsible for the only weak biological activity of unmodified PNA.     

Nucleobase modifications in peptide nucleic acids

Peptide nucleic acid (PNA) is an oligonucleotide mimic originally designed upon a repeating N-(2-aminoethyl)glycine polyamide backbone to which nucleobase heterocycles are attached through a methylene carbonyl linkage to the alpha-amino group. These molecules possess remarkable hybridization properties with DNA or RNA forming complexes with high stability and with excellent sequence discrimination despite the substantial structural divergence from natural nucleic acids. Since the disclosure of PNA, a vibrant research community with interest in the chemistry and applications of polyamide-based nucleic acid analogs has developed. This has led to the synthesis and evaluation of a wide variety of modified polyamide nucleic acids. The focus of this report is a comprehensive review of nucleobase modifications in aminoethylglycine (aeg) PNA with reference, where appropriate, to the same modification in DNA or RNA.     

Targeting serum antibody for cancer diagnosis: a focus on colorectal cancer

The ability of the immune system to magnify the appearance of disease by generating relatively large amounts of antibody in response to small amounts of disease makes it a natural biosensor, and serum antibodies have emerged as promising biomarkers for the detection of cancer. This review summarizes recent progress in targeting serum antibodies for cancer diagnosis, with a particular focus on colorectal cancer (CRC). Several serum antibodies have been detected at increased levels in CRC patients, including p53, carcinoembryonic antigen, Ras, topoisomerase II-alpha, histone deacetylase 3 and 5, ubiquitin C-terminal hydrolase L3, tropomyosin and cyclin B1. As each antibody is only present in a limited proportion of patients (usually < 40%), a combination of serum antibodies that defines the 'immunological signature' of cancer needs to be developed. High-throughput methods to identify new serum antibodies for cancer diagnosis are also reviewed.     

Catalytic nucleic acids: from lab to applications

Since the discovery of self-cleavage and ligation activity of the group I intron, the expansion of research interest in catalytic nucleic acids has provided a valuable nonprotein resource for manipulating biomolecules. Although a multitude of reactions can be enhanced by this class of catalyst, including trans-splicing activity of the group I intron (which could be applied to gene correction), RNA-cleaving RNA enzymes or "ribozymes" hold center stage because of their tremendous potential for mediating gene inactivation. This application has been driven predominantly by the "hammerhead" and "hairpin" ribozymes as they induce specific RNA cleavage from a very small catalytic domain, allowing delivery either as a transgene expression product or directly as a synthetic oligonucleotide. Although advances in the development of RNA modifications have improved the biological half-life of synthetic ribozymes, their use is restricted by the mechanistic dependence on conserved 2'OH-moieties. Recently a new class of catalytic nucleic acid made entirely of DNA has emerged through in vitro selection. DNA enzymes or deoxyribozyme with extraordinary RNA cleavage activity has already demonstrated their capacity for gene suppression both in vitro and in vivo. These new molecules, although rivaling the activity and stability of synthetic ribozymes, are limited equally by inefficient delivery to the intracellular target RNA. The challenge of in vivo delivery is being addressed with the assessment of a variety of approaches in animal models with the aim of bringing these compounds closer to the clinic.     

甲状腺癌诊断、治疗及预后因素的分析

目的：探讨甲状腺癌的诊断、治疗及预后因素,为临床治疗效果的进一步提高提供新的思路和新的资料。方法：回顾性分析2000年1月～2006年1月本院病理并外科手术治疗确诊的100例甲状腺癌的临床资料。结果：甲状腺癌5年生存率为93.1%。多因素分析发现：分期、性别、年龄、手术方式是影响预后的因素。结论：分期、年龄、手术方式是影响预后的独立因素,根据不同患者的特点进行预后因素的评估,优化地选择治疗方案,从而获得合理正确的手术方案,才能提高患者的生存率,改善预后。     

结直肠癌伴神经内分泌分化的临床诊疗及预后分析

目的 探讨结直肠癌伴神经内分泌分化的临床诊疗,并对预后进行分析。方法 回顾性分析安阳市人民医院2001年5月到2007年5月期间收治的280例结直肠癌患者的临床病理资料,比较伴与不伴神经内分泌细胞分化的两组结直肠癌患者的临床病理特征。结果 280例结直肠癌患者中有25例伴有神经内分泌细胞分化,其中CgA阳性18例（72％）,Syn阳性15例（60％）,CgA与Syn同时阳性8例。结论 结直肠癌发生神经内分泌细胞分化的机理尚未完全清楚,免疫组织化学染色是诊断结直肠癌伴神经内分泌分化的有效方法 ,伴神经内分泌分化可能成为影响结直肠癌预后不良的重要因素之一。     

血清肿瘤标志物AFP、CEA联合检测对原发性肝癌的诊断及预后评估价值分析

目的探讨血清肿瘤标志物甲胎蛋白、癌胚抗原联合检测对原发性肝癌的诊断及预后评估价值。方法选择我院2016年1月～2017年6月收治的经病理检查确诊为原发性肝癌患者27例为研究对象,另选择同期收治的肝炎肝硬化患者30例和体检健康者30例为观察对象,均进行血清肿瘤标志物AFP、CEA联合检测,记录其检测结果,并评估其预后价值。结果原发性肝癌患者AFP、CEA水平均明显高于肝炎肝硬化组和健康组(P<0.05);原发性肝癌组患者AFP、CEA联合检测阳性率均显著高于肝炎肝硬化组和健康组(P<0.05),原发性肝癌组患者AFP、CEA联合检测阳性率高于单一检测(P<0.05);AFP、CEA联合检测对原发性肝癌敏感度高于单一指标(P<0.05)。结论血清肿瘤标志物AFP、CEA联合检测对原发性肝癌诊断敏感性较强,具有较高临床价值。     

2型糖尿病患者血尿酸与蛋白尿的关系

目的 探讨2型糖尿病（T2DM）患者血尿酸（SUA）与蛋白尿的关系。方法 选择2016年5月至2017年9月安徽省立医院住院的T2DM患者791例,根据血尿酸（SUA）水平将患者分为正常尿酸（NUA）组656例和高尿酸（HUA）组135例,通过单因素分析比较两组患者尿白蛋白/肌酐（UACR）的差异;通过Pearson相关分析,比较UACR与其他生化指标的相关性,并将有统计学意义的指标纳入logistic回归分析中,了解SUA对蛋白尿发生的相对危险度。结果 ①HUA组患者UACR高于NUA组,差异有统计学意义（P<0.05）;HUA组患者蛋白尿的发生率（54.8%）高于NUA组（38.6%）,差异有统计学意义（P<0.05）;②Pearson相关分析显示,UACR与SUA呈正相关（P<0.05）;Logistic回归分析显示,血尿酸水平每增加1 mg/dL,发生蛋白尿的相对危险度为1.096（P=0.005）。结论 T2DM患者中,血尿酸水平升高可引起UACR升高,是蛋白尿发生的危险因素,在糖尿病的治疗中需监测血尿酸水平。