子宫颈腺癌组织中癌胚抗原和甲胎蛋白的检测

采用免疫金银染色技术,对64例子宫颈腺癌组织进行了癌胚抗原(CEA)和甲胎蛋白(AFP)的免疫组化检测.结果表明,CEA和AFP的阳性率分别为75.00%和14.06%.不同分化程度组织间,CEA阳性率无显著性差异(P>0.05),但在不同组织学类型间,CEA阳性率差异有显著性意义(P<0.05).提示对子宫颈腺癌组织进行CEA检验,有助于其组织学分类.     

Shark variable new antigen receptor biologics – a novel technology platform for therapeutic drug development

Introduction: Biologics drugs have succeeded in achieving a commercial dominance in the global market for new therapies and large pharmaceutical companies' interest remains strong through a continued commitment to pipeline development. It is not surprising, therefore, that next-generation biologics, particularly antibody-like scaffolds that offer many of the advantages of the original biologic drugs but in simplified formats, have entered the clinic as competing substitute therapeutic products, to capture market share.

Areas covered: Specifically, this paper will position shark-derived variable new antigen receptors (VNARs) within an overview of the existing biologics landscape including the growth, diversity and success to date of alternative scaffolds. The intention is not to provide a comprehensive review of biologics as a whole but to discuss the main competing single-domain technologies and the exciting therapeutic potential of VNAR domains as clinical candidates within this context.

Expert opinion: The inherent ability to specifically bind target and intervene in disease-related biological processes, while reducing off-site toxicity, makes mAbs an effective, potent and now proven class of therapeutics. There are, however, limitations to these ‘magic bullets’. Their size and complexity can restrict their utility in certain diseases types and disease locations. In contrast, a number of so-called alternative scaffolds, derived from both immunoglobulin- and non-immunoglobulin-based sources have been developed with real potential to overcome many of the shortcomings documented for mAb treatments. Unlike competing approaches such as Darpins and Affibodies, we now know that shark VNAR domains (like camel VHH nanobody domains), are an integral part of the adaptive immune system of these animals and have evolved naturally (but from very different starting molecules) to exhibit high affinity and selectivity for target. In addition, and again influenced by the environment in which they have evolved naturally, their small size, simple architecture, high solubility and stability, deliver additional flexibility compared to classical antibodies (and many non-natural alternative scaffolds), thereby providing an attractive basis for particular clinical indications where these attributes may offer advantages.     

Ipilimumab in non-small cell lung cancer and small-cell lung cancer: new knowledge on a new therapeutic strategy

The challenge of finding a lasting cure for autoimmune disease(s) has not been met. Although the use of systemic anti-inflammatory agents still dominates the treatment of these diseases, there is a push towards developing novel and more specific strategies. In addressing autoimmunity, there is the intrinsic need to understand the mechanisms that lead to the development and maintenance of immunological tolerance to self-antigens. Experimental evidence has shown that directed antigen expression in the thymus can induce immunological tolerance to that antigen. This forms the cornerstone of one strategy directed towards the cure of autoimmunity. In this strategy, individuals with autoimmune disease are transplanted with bone marrow stem cells that have been genetically modified and in this way allow expression of the self-antigen in the thymus.     

结肠癌淋巴结转移与活体组织中血管内皮生长因子的关系

目的　探讨结肠癌活体组织中血管内皮生长因子 (VEGF)、p5 3蛋白和增殖细胞核抗原 (PCNA)表达与淋巴结转移的关系。方法　应用病理学诊断方法检查淋巴结有无癌细胞转移 ,结肠癌组织标本作VEGF、p5 3蛋白和PCNA免疫组织化学染色。 结果　VEGF阳性表达结肠癌患者淋巴结转移率为 61.90 % ( 13 /2 1) ,VEGF阴性结肠癌淋巴结转移率为 2 6.67% ( 12 /4 5 ) ,差异有非常显著性 ( χ2 =7.5 5 5 7,P <0 .0 1) ;而 p5 3及PCNA阳性表达结肠癌患者淋巴结转移和阴性表达结肠癌患者的淋巴结转移之间差异无显著性 (P >0 .0 5 )。结论　结肠癌组织中VEGF的表达可为结肠癌患者的淋巴结转移情况的判断及预后提供参考。     

基于石墨烯-依来铬青蓝R的新型免标记电化学免疫传感器用于CA19-9检测

目的构建石墨烯-依来铬青蓝R(GO-ECR)免标记电化学免疫传感器高灵敏检测CA19-9的新技术。方法化学法合成氧化石墨烯并滴涂于电极表面,通过循环伏安法电沉积制作GO-ECR修饰玻碳电极,在偶联剂EDC和NHS作用下以共价键合方式将CA19-9抗体固定于修饰电极表面,固定的抗体与CA19-9发生免疫反应形成抗原-抗体复合物。铁氰化钾溶液作为检测探针,对比免疫反应前后铁氰化钾响应信号的差异,利用信号降低程度与CA19-9浓度正相关,实现对CA19-9的特异性高灵敏检测。结果该电化学免疫传感器检测CA19-9的线性范围为0.05～500 U/mL,检测限为0.01 U/mL,且能准确测定临床血清样本CA19-9的浓度。结论构建的GO-ECR免标记电化学免疫传感器可以简单、准确、特异地检测CA19-9。     

中国人惰性前列腺癌临床筛选标准的比较

目的:依据临床病理资料对目前国际上使用最广泛的5种术前判断惰性前列腺癌的筛选标准进行探讨,以探索这些标准对国人惰性前列腺癌筛查的有效性.方法:回顾性分析2006年1月至2014年4月,314例于北京大学第一医院行前列腺穿刺活检确诊,并行根治性前列腺切除术的前列腺癌患者的临床病理及手术病理资料.以手术病理Gleason评分≤6、分期T2、癌灶总体积≤0.5 mL作为惰性前列腺癌的病理标准,对比国际上研究较多的5种判断惰性前列腺癌的临床标准,分别为Epstein标准(EC)、Sloan-Kettering纪念肿瘤中心标准(Memorial Sloan-Kettering Cancer Center,MSKCC)、国际前列腺癌研究-主动监测标准(Prostate Cancer Research International:Active Surveillance,PRIAS)、UCSF标准(University of California,San Francisco,UCSF)和UM标准(University of Miami,UM),对灵敏度、特异度以及受试者工作特性曲线下面积(areas under the receiver-operating curve,AUC)等指标进行统计分析,探讨各方法预测惰性前列腺癌的效能差异.结果:临床病理资料中,共有49例(16％)病例符合5种标准中的任意一种筛选标准,不考虑重复计算,其中符合Epstein标准者24例、符合MSKCC者33例、符合PRIAS者28例、符合UCSF者34例、符合UM标准者22例,仅8例(3％)符合全部标准.手术病理中,共24例(8％)符合惰性前列腺癌的病理标准.通过比较临床病理与手术病理资料,UCSF、MSKCC两标准在敏感性和特异性上均有良好的表现,AUC也大于其他3种标准,统计效能较高;Epstein、PRIAS两标准的阳性预测值较高,敏感性、特异性略低,统计效能中等;UM标准的敏感性、阳性预测值及AUC都较低,统计效能显著低于其他4种标准;符合全部5种筛选标准不能提高统计效能.结论:UCSF标准筛选惰性前列腺癌的预测效能高于其他标准,但其准确性仍较低,符合全部5种筛选标准并不能提高预测效能,此结果与国外大样本结果并不完全一致,因此需要进一步探讨更适合中国人的筛选模型.     

瘢痕Bcl-2基因与细胞增殖和凋亡的关系

目的:探讨增生性瘢痕成纤维细胞Bcl-2基因表达水平与细胞增殖活性及凋亡程度的关系。方法:用原位杂交、免疫组化染色ABC法,对79例增生性瘢痕组织分别检测Bcl-2mRNA、Bcl-2蛋白和增殖细胞核抗原的表达,并用TUNEL法作原位细胞凋亡检测。结果:75例（94.9％）表达Bcl-2mRNA,70例（88.6％）表达Bcl-2蛋白,两者表达水平呈正相关（rs=0.989,P<0.01）;随成纤维细胞Bcl-2蛋白表达水平升高其增殖活性相应增加,而凋亡相应减少,Bcl-2蛋白+++组与++组（P<0.05）及前两组分别与-组和+组间（P<0.01）两项指标差异均有显著性。结论:增生性瘢痕中成纤维细胞Bcl-2基因高表达可抑制其凋亡,可能由此引起的细胞凋亡减少与其他基因异常所致的细胞过度增殖共同导致瘢痕的形成。     

Feasibility study: watchful waiting for localized low to intermediate grade prostate carcinoma with selective delayed intervention based on prostate specific antigen, histological and/or clinical progression

PURPOSE: We assessed the feasibility of a watchful waiting protocol with selective delayed intervention using clinical, prostate specific antigen (PSA) or histological progression as treatment indications for clinically localized prostate cancer. MATERIALS AND METHODS: In this prospective, single arm cohort study patients with favorable clinical parameters (stage T1b to T2b N0M0, Gleason score 7 or less and PSA 15 ng./ml. or less) are conservatively treated with watchful waiting. When a patient meets disease progression criteria, arbitrarily defined by the 3 parameters of the rate of PSA increase, clinical progression or histological upgrade on repeat prostate biopsy, appropriate treatment is implemented. Patients are followed every 3 months for the first 2 years and every 6 months thereafter. Serum PSA measurement and digital rectal examination are done at each visit and repeat prostate biopsy is performed 18 months after study enrollment. RESULTS: Since November 1995, the study has accrued 206 patients with a median followup of 29 months (range 2 to 66). Of these men 137 remain on the surveillance protocol with no disease progression, while 69 were withdrawn from study for various reasons. There was clinical, PSA and histological progression in 16, 15 and 5 cases, respectively. The estimated actuarial probability of remaining on the surveillance protocol was 67% at 2 years and 48% at 4. The probability of remaining progression-free was 81% and 67% at 2 and 4 years, respectively. CONCLUSIONS: A policy of watchful waiting with selectively delayed intervention based on predefined criteria of disease progression is feasible. This strategy offers the benefit of an individualized approach based on the demonstrated risk of clinical or biochemical progression with time and, thus, it may decrease the burden of therapy in patients with indolent disease, while providing definitive therapy for those with biologically active disease.     

Impact of HLA-compatibilities in patients undergoing liver transplantation for HBV-cirrhosis

Liver transplantation (OLT) for end-stage chronic hepatitis-B-virus (HBV) infection is frequently complicated by HBV recurrence. In the present study we investigated whether human leucocyte antigen (HLA)-matching influences the outcome after OLT. In a retrospective analysis we reviewed 84 recipients of liver transplants for end-stage HBV-cirrhosis and complete HLA-typing for outcome after OLT. Follow-up ranges from 1 to 110 months (median = 55.6 months). Immunosuppression consisted of Cyclosporin A (CsA)-based quadruple induction therapy or Tacrolimus-based induction protocols. Immunoprophylaxis with hepatitis B immunoglobulin was started at OLT and continued long-term. Actuarial 1- and 5-yr graft survival figures were 90.5 and 80.4%, respectively. Hepatitis-B recurrence was responsible for 15 of 20 (75%) graft failures. We observed a significantly improved graft survival in patients with more HLA-A, -B compatibilities (p = 0.02), whereas the degree of HLA-DR compatibilities did not influence the outcome. The occurrence of HBV-reinfection was significantly lower in HLA-A, -B matched grafts (p < 0.05). Additionally, graft survival was prolonged in patients with HBV-reinfection and 1 or 2 HLA-B compatibilities when compared with patients with HBV-reinfection and a complete HLA-B mismatch (p = 0.02). In conclusion, this retrospective analysis shows that more HLA-A, -B compatibilities seems to be associated with an improved graft survival in patients after OLT for end-stage HBV infection.