原发性肝癌患者外周血甲胎蛋白mRNA表达水平及其意义

甲胎蛋白（AFP）是肝癌发生、发展过程中表达的蛋白质,长期以来被认为是标志性蛋白而用于肝癌的早期诊断;但灵敏度和特异性均不够理想,尤其是它不能反映肝癌有无转移,而及早发现微小病灶对于原发性肝癌（PHC）患者治疗具有重要意义。近年来国外研究者用高敏感的反转录聚合酶链反应（RT—PCR）技术在肿瘤患者的循环血液中查找癌细胞,用于早期发现PHC患者外周血中是否存在肝癌细胞。这对于肝癌的早期诊断、预防及治疗有着重要的指导意义。     

原发性肝癌肿瘤标记物研究进展

原发性肝癌（PHC）的发病率和病死率均居于我国恶性肿瘤的前三位。上海复旦大学肝癌研究所对高危人群每6个月监测AFP和腹部超声，发现肝癌筛查能降低肝癌病死率的37％。但国内外研究表明，近1／3的PHC患者甲胎蛋白（AFP）阴性。因此，寻找肝癌特异性早期诊断方法，是目前临床亟待解决的难题。现就目前临床上应用的和新发现的PHC肿瘤标记物综述如下。     

原发性肝癌患者外周血中AFPmRNA检测的临床意义

通过定量检测AFPmRNA在原发性肝癌（PHC）患者外周血中的表达,探讨AFPmRNA作为PHC患者早期诊断和微转移指标的可能性。建立荧光定量聚合酶链式反应（FQ-PCR）,检测58例外周血AFPmRNA的表达量。其中,30例PHC患者中19例AFP≥20ng/m l,23例外周血中AFPmRNA有表达;肝癌患者外周血中AFPmRNA的基因拷贝数与肝癌患者有肝内外转移有明显相关,而肝炎及健康对照组外周血中AFPmRNA均未表达,肝硬化组有一例表达。应用荧光定量PCR检测PHC外周血中AFPmRNA表达情况,可以作为早期反映PHC患者外周血中是否存在肝癌细胞和发生微转移的早期灵敏指标。     

肝癌特异诊断新标志物发现及其临床应用前景

肝细胞癌(hepatocellular carcinoma,HCC)是全球的最常见的肿瘤之一.虽经持续不懈地根除或改进多种治疗技术,肝癌患者的预后仍很差.如何监测肝细胞的恶性转化或早期诊断HCC仍是医学难题.HCC发病机制复杂,多种致病因素包括乙型肝炎病毒或丙型肝炎病毒的慢性持续感染、脂质积聚和黄曲霉素摄入等致使抗癌基因失活或癌基因复活,诱发肝细胞癌变;HCC患者的早期筛查有益于延长生存期.血甲胎蛋白(alpha-fetoprotein,AFP)和肝癌特异性AFP或A F P-L3作为肿瘤标志虽已常规应用,但他们诊断肝癌仍存在假阳性结果且灵敏度及特异性欠佳.肝癌的有效治疗取决于早期诊断,急需研发比较准确有效标志物用于肝癌患者的早期临床分期,治疗监测与预后判断.近来,积累的资料已显示新的血源性标志物如循环血肿瘤细胞,相关通路关键信号分子、癌胚型特异蛋白、长链非编码RNA和微小RNA对肝癌诊断的潜在价值.本文述评了肝癌特异诊断相关分子标志发现及其应用前景.     

血清肿瘤标志物DR-70^TM对原发性肝癌的诊断价值

目的评价血清肿瘤标志物DR-70^TM在原发性肝癌中的诊断价值，提高原发性肝癌（PHC）的检出率。方法应用美国AMDL公司的DR-70^TMELISA试剂盒，对20例正常人和60例AFP阳性原发性肝癌、43例AFP阴性原发性肝癌及30例肝硬化病人血清进行检测DR-70含量。结果原发性肝癌组血清DR-70^TM含量明显高于肝硬化组和正常对照组（P均〈0．001），AFP阳性原发性肝癌DR-70的阳性率为81．67％，AFP阴性原发性肝癌为93．02％，差异有显著性（P〈0．05）。DR-70^TM诊断肝癌敏感性为86．4％，特异性为94％；肝硬化组阳性率10％，特异性90％。肝硬化组与正常组比较差异无显著性（P〉0．05）；DR-70^TM与癌肿（直径）大小无明显关系（P〉0．05）。结论血清DR-70和AFP联合检测可大大提高原发性肝癌的阳性率，有利于原发性肝癌的早期诊断，特别是AFP阴性的肝癌的有价值的标志物。也有利于PHC与肝硬化（LC）的鉴别诊断。对非恶性肿瘤病人特异性较高，对人群筛选将有较高的参考价值。     

几种较特异的肝癌标志对原发性肝癌的临床意义

目前,甲胎蛋白(AFP)仍是诊断原发性肝癌(PHC)的最特异的标志,但尚有10～30%的PHC患者其血清AFP为阴性,35～40%的PHC患者血清AFP测定值<400ng/ml。这些AFP低浓度阳性或阴性PHC以及某些良性肝病患者出现的AFP假阳性,给临床诊断带来一定的困难。为此,还需寻找AFP以外的肝癌标志以弥补AFP的不足。本文依据现有的一些国内外资料,试对几种目前较为肯定的肝癌标志,尤其是对AFP低浓度阳性或阴性PHC的临床意义,作一综述。     

肝癌早期诊断标志物研究进展

肝癌 (HCC)是我国常见的恶性肿瘤 ,其死亡率位于第二位。所有HCC几乎都有肝硬化基础 ,确诊时已多属中、晚期 ,缺乏有效治疗 ,预后差。虽HCC非手术疗法有进展 ,但手术切除仍是目前最有效的治疗方法[1 ,2 ] 。晚期HCC切除后复发率高 ,易转移 ,早期诊断极为重要。肝癌血清标志物众多 ,尚无单一标志物能够诊断所有肝癌。敏感而特异如甲胎蛋白AFP L3、异常凝血酶原 (PIVKA Ⅱ )、肝癌特异性GGT等标志物 ,它们间无相关性并起互补作用。肝癌标志物分析有助于肝癌早期诊断、疗效观察及术后随访、复发或转移监测[3 ] 。本文就早期诊断有价…     

肝细胞恶性转化与监测分子标志

早诊早治是提高肝细胞癌患者生存率的唯一途径。随着基因组学、蛋白组学、转录组学和代谢组学等多种“组学”技术的进展，愈来愈多的肝细胞恶性转化相关分子标志被发现，并有望成为肝癌发生的预警监测及早期诊断的特异性生物标志。     

癌胚型GPC-3特异诊断原发性肝细胞癌及其靶向治疗进展

原发性肝细胞性肝癌(primary hepatocellular cancer,PHC)的发生、发展是一个多因素、多步骤、多中心的复杂过程,他的早期诊断和有效治疗至关重要.磷脂酰肌醇蛋白多糖-3(glypican-3,GPC-3)在PHC进展过程中起重要作用.在肝细胞恶性转化过程中G P C-3呈进行性升高表达;人肝癌G P C-3阳性率与乙型肝炎表面抗原(hepatitis B surface antigen,Hbs Ag)、TNM分期、门脉癌栓及肝外转移显著相关.GPC-3及m RNA与甲胎蛋白(alpha fetoprotein,AFP)联合检测,对PHC诊断阳性率可提高至94.3%;沉默GPC-3可改变肝癌细胞迁移、转移和侵袭的生物学行为,伴随β-catenin、p-糖原合成激酶3β(pglycogen synthase kinase 3β,p-GSK3β)和cyclin D1表达明显减少,提示癌胚性GPC-3不仅是PHC特异诊断标志物,而且有可能成为PHC治疗的潜在靶点.     

中药提取物榄香烯治疗原发性肝癌的研究进展

<正>原发性肝癌(PHC)是指发生于肝细胞或肝内胆管细胞的恶性肿瘤，起病隐匿，早期症状不明显，使得PHC临床治疗比较棘手^[1]。最新流行病学数据显示，2020年PHC在中国常见新发癌症中排名第5位，在我国有超过41万人新患PHC,有超过39万人死于PHC^[2]。目前PHC常用治疗手段包括手术治疗、局部治疗、放射治疗、化疗、分子靶向治疗、中医药治疗及免疫治疗。但是由于PHC早期诊断困难，发展迅速，大部分患者就诊时已是中晚期或出现转移，     

Progress in diagnosis and surgical treatment of perihilar cholangiocarcinoma

Cholangiocarcinomas are heterogeneous biliary tract tumors that cause devastating disease. Perihilar cholangiocarcinoma (PHC) is the most common type of biliary tract cancer and are associated with a high mortality. Diagnoses of PHC depend on the results of its clinical presentation, serum biomarkers and imaging techniques. Pre-operative managements including pre-operative biliary drainage (PBD) and portal vein embolization (PVE) could reduce mortality. The best chance of long-term survival and potential cure is surgical resection with negative surgical margin. Lymph node metastasis over N2 nodes precludes long-term survival. The benefit of concomitant vascular resection remains uncertain. Liver transplantation combined with neoadjuvant chemotherapy with radiotherapy is a promising option in highly selected patients with unresectable tumors. Herein, an overview is provided of developments in diagnosis, peri-operative management and surgical treatment among patients with PHCs.     

循环microRNA早期诊断肝细胞癌研究现状及方法学探讨

肝细胞癌（HCC）是发病率和死亡率很高的恶性肿瘤,对高危人群的筛查和监测十分重要。定期检查肝脏超声和血清AFP是目前主要的筛查手段,但灵敏度和准确性仍不尽如人意。microRNA与HCC的发生、转移、复发等病理过程密切相关,相关研究也方兴未艾。循环microRNA是HCC血清学标志物中的重要成员,在HCC诊断和筛查方面具有广阔的应用前景。选择合适的microRNA和确定高效的诊断方法是相关研究的重点,更多高质量的研究还在持续进行中。     

原发性肝癌的实验室诊断

原发性肝癌是指原发于肝脏的上皮源性恶性肿瘤,主要包括肝细胞癌和肝内胆管细胞癌。实验室检查是原发性肝癌诊断的重要手段,其中临床病理学检查是原发性肝癌诊断的"金标准"。随着精准医学概念的提出和个体化治疗的迅猛发展,实验室检查在原发性肝癌早期诊断、靶向分子鉴定、肿瘤监测和预后评估等方面承担了更多的责任。本文对原发性肝癌的实验室诊断作一综述。     

Use of Biomarkers in the Management of Children with Lupus

Childhood systemic lupus erythematosus (SLE) is known to have a worse prognosis than adult-onset disease, and monitoring and treatment of the disease are still a challenge. Thus, there is an urgent need for highly reliable, non-invasive biomarkers for early detection of relapses, to avoid long-term complications and to optimize the management of children with LN. Recent studies of pediatric patients have yielded novel specific biomarkers for SLE diagnosis which can be used for monitoring disease activity and response to treatment. The most promising biomarkers in juvenile-onset SLE include cell-bound complement activation products, some genomic profiles, and urinary proteins such as neutrophil gelatinase-associated lipocalin, monocyte chemoattractant protein-1, and alpha-1-acid glycoprotein. None of these might be suitable for use as a single SLE-biomarker. More likely a combination of novel biomarkers with traditionally used data, including autoantibodies and complement, might help to enhance sensitivity and specificity for early diagnosis, disease monitoring, and prediction of relapses.cp     

新发糖尿病——胰腺癌早期筛查和诊断的临床线索

胰腺癌是一种高度恶性的消化系统恶性肿瘤,因其起病隐匿、缺乏有效特异的早期筛查手段,发现时多为晚期,已失去手术时机,预后很差。糖尿病是胰腺癌发生的危险因素,新发糖尿病可能是胰腺癌的病因或早期表现之一,有助于胰腺癌的早期发现与诊断;而不同降糖药物的应用可能对胰腺癌的发生具有一定影响。在糖尿病患者中发现胰腺癌的特异性血清微小RNA(microRNA),可能成为未来胰腺癌早期筛查和预后监测的非侵入性生物标志物。     

Diagnostic and prognostic biomarkers in cholangiocarcinoma

The high mortality rate of cholangiocarcinoma (CCA) is due, in part, to the lack of non‐invasive approaches able to accurately detect this silent tumour at early stages, when therapeutic options can be potentially curative or may at least increase the overall survival of patients. The fact that the majority of CCA tumours are not linked to any known aetiological factor highly compromises the monitoring of patients at risk for tumour development and also their early diagnosis. Combination of clinical/biochemical features, imaging techniques and analysis of non‐specific tumour biomarkers in serum are commonly used to help in the diagnosis of CCA, but tumour biopsy is usually required to confirm the diagnosis. Moreover, no prognostic biomarkers are currently used in the clinical setting, deserving more innovative research, and international validation and consensus. Important efforts have been made in the last few years to identify accurate non‐invasive biomarkers, by using innovative techniques and high‐throughput omics technologies. This review summarizes and discusses the advances in the investigation of novel diagnostic and prognostic biomarkers in CCA and envisions the future directions in this field of research.     

Biomarkers in asthma and allergic rhinitis

A biological marker (biomarker) is a physical sign or laboratory measurement that can serve as an indicator of biological or pathophysiological processes or as a response to a therapeutic intervention. An applicable biomarker possesses the characteristics of clinical relevance (sensitivity and specificity for the disease) and is responsive to treatment effects, in combination with simplicity, reliability and repeatability of the sampling technique. Presently, there are several biomarkers for asthma and allergic rhinitis that can be obtained by non-invasive or semi-invasive airway sampling methods meeting at least some of these criteria.In clinical practice, such biomarkers can provide complementary information to conventional disease markers, including clinical signs, spirometry and PC₂₀methacholine or histamine. Consequently, biomarkers can aid to establish the diagnosis, in staging and monitoring of the disease activity/progression or in predicting or monitoring of a treatment response. Especially in (young) children, reliable, non-invasive biomarkers would be valuable.Apart from diagnostic purposes, biomarkers can also be used as (surrogate) markers to predict a (novel) drug’s efficacy in target populations. Therefore, biomarkers are increasingly applied in early drug development.When implementing biomarkers in clinical practice or trials of asthma and allergic rhinitis, it is important to consider the heterogeneous nature of the inflammatory response which should direct the selection of adequate biomarkers. Some biomarker sampling techniques await further development and/or validation, and should therefore be applied as a “back up” of established biomarkers or methods. In addition, some biomarkers or sampling techniques are less suitable for (very young) children. Hence, on a case by case basis, a decision needs to be made what biomarker is adequate for the target population or purpose pursued.Future development of more sophisticated sampling methods and quantification techniques, such as – omics and biomedical imaging, will enable detection of adequate biomarkers for both clinical and research applications.     

结直肠癌生物标志物的研究进展

结直肠癌(CRC)是严重影响人类健康的恶性疾病之一。约25%的CRC患者在初诊时已经发生远处转移，这类患者预后极差。高预测性能的生物标志物能早期精准检出CRC并精确预测疗效。近年来，多项研究指出炎性标志物、非编码RNA、肠道菌群、循环肿瘤细胞等指标具备CRC诊断及预后预测能力。本文就CRC生物标志物的研究进展进行讨论，以期为CRC的诊治提供思路。     

New frontiers in biomarkers for hepatocellular carcinoma

Hepatocellular carcinoma represents the fifth most frequent cancer in the world; it commonly occurs on cirrhotic liver. Prognosis and survival are still poor, mainly because of diagnosis at a late stage and/or recurrence of the disease. For this reason, surveillance strategies are widely used to screen for early occurrence of cancer in populations at risk. Alpha-foetoprotein is so far the only serological marker available, but its diagnostic accuracy is unsatisfactory because of low sensitivity despite reliable specificity. For this reason, new biomarkers for the diagnosis of hepatocellular carcinoma are in strong demand by clinicians. In this review, we will focus on new biomarkers currently under investigation, but also on still newer, very promising biomarkers that seem to significantly improve diagnosis.     

MicroRNAs as potential biomarkers for gastric cancer

Gastric cancer is the fourth most common cancer in the world and the second leading cause of cancerrelated death.More than 80%of diagnoses occur at the middle to late stage of the disease,highlighting an urgent need for novel biomarkers detectable at earlier stages.Recently,aberrantly expressed microRNAs(miRNAs)have received a great deal of attention as potential sensitive and accurate biomarkers for cancer diagnosis and prognosis.This review summarizes the current knowledge about potential miRNA biomarkers for gastric cancer that have been reported in the publicly available literature between 2008 and 2013.Available evidence indicates that aberrantly expressed miRNAs in gastric cancer correlate with tumorigenesis,tumor proliferation,distant metastasis and invasion.Furthermore,tissue and cancer types can be classified using miRNA expression profiles and next-generation sequencing.As miRNAs in plasma/serum are well protected from RNases,they remain stable under harsh conditions.Thus,potential functions of these circulating miRNAs can be deduced and may implicate their diagnostic value in cancer detection.Circulating miRNAs,as well as tissue miRNAs,may allow for the detection of gastric cancer at an early stage,prediction of prognosis,and monitoring of recurrence and/or lymph node metastasis.Taken together,the data suggest that the participation of miRNAs in biomarker development will enhance the sensitivity and specificity of diagnostic and prognostic tests for gastric cancer.