Carbonic Anhydrase IX in Renal Cell Carcinoma: Implications for Prognosis,Diagnosis, and Therapy

Context

The clinical management of patients with renal cell carcinoma (RCC) remains difficult, and the development of new diagnostic, prognostic, and therapeutic tools is still required.

Objective

To review the current knowledge on the RCC-associated antigen carbonic anhydrase IX (CAIX) and provide evidence for how this antigen may aid in the clinical management of RCC.

Evidence acquisition

Clinical papers describing diagnostic, prognostic, and/or therapeutic applications of CAIX in RCC were selected from the Pubmed database. The search was manually augmented by reviewing the reference lists of articles.

Evidence synthesis

Expression of CAIX is regulated by the Von Hippel Lindau (VHL) protein (pVHL). Because of the invariable VHL mutational loss in clear-cell RCC (ccRCC) patients, CAIX expression is ubiquitous in ccRCC. Determination of CAIX expression in nephrectomy specimens of RCC patients improves prognostic accuracy; high CAIX expression appears to correlate with a favourable prognosis and a greater likelihood of response to systemic treatment for metastatic disease. Therefore, CAIX expression might be used to stratify metastatic ccRCC (mRCC) patients for systemic treatment. When incorporated into the RCC nomogram, CAIX expression seems to improve diagnostic accuracy for primary RCC as well as mRCC patients, but further evidence is required. Clinical studies with the CAIX-specific monoclonal antibody (mAb) cG250 have provided unequivocal evidence that ccRCC lesions can be imaged with radiolabeled cG250. Results are awaited of a large, randomised trial that aims to establish the value of cG250 imaging for primary RCC. The outcome of another large, placebo-controlled study is awaited to establish the usefulness of CAIX-targeted therapy in the adjuvant setting. Therapeutic trials with high-dose radiolabeled cG250 and CAIX-loaded dendritic cells in mRCC patients are still in phase 1 or 2.

Conclusions

CAIX improves diagnostic accuracy and is an attractive target for imaging of and therapy for ccRCC.     

血清 CA19-9 水平在良性胆管疾病患者中的临床意义

背景: CA19-9是临床常用的肿瘤标记物,对胰胆系恶性肿瘤的阳性率较高,但良性胆管疾病中亦常见CA19-9水平升高。目的: 分析血清CA19-9水平在良性胆管疾病患者中的临床意义。方法: 选取2004年10月～2009年5月北京军区总医院的78例经ERCP证实的良性胆管疾病患者(60例胆总管结石和18例胆总管炎性狭窄)。所有患者于ERCP术前行血清CA19-9水平检测,并分析其在良性胆管疾病中的临床意义。结果: 39例(50.0%)患者血清CA19-9水平正常,其中胆总管结石26例(66.7%)。其余39例(50.0%)患者血清CA19-9水平升高,其中胆总管结石34例(87.2%);4例血清CA19-9水平1000U/ml者的年龄均65岁,并合并有严重化脓性梗阻性胆管炎或重症急性胰腺炎。16例血清CA19-9升高者于ERCP术后行复查,多数患者血清CA19-9水平明显下降。结论: 良性胆管疾病患者中血清CA19-9水平可升高,可作为预测胆管炎症程度的指标,尤其是在老年患者中。     

乙型肝炎病毒感染在IgA肾病发病中的作用的进一步研究

目的：探讨乙型肝炎病毒（HBV）感染与IgA肾病发病的关系。方法：采用免疫组化技术检测168例IgA肾病患者肾组织中HBV抗原（HBAe）,应用原位分子杂交技术和Southern印迹杂交技术检测95例IgA肾病患者肾组织中HBVDNA。结果：168例IgA肾病患者中,血清HBsAg阳性32例（19．05％）;肾组织HBAg阳性59例（35．12％）,HBAg在肾小球中阳性率为30．36％（51／168）,其中HBsAg为27．98％（47／168）,HBcAg为24．40％（41／168）;除了肾小球,H13sA4g和HBcAg肾小管上皮细胞亦有阳性沉积,分别为44例（26．19％）和48例（28．57％）;Smthem印迹杂交证实在95例患者肾组织中46例有整合型HBVDNA,阳性率为48．42％;原位分子杂交证实95例患者肾组织HBVDNA阳性率为52．63％（50／95）,其中肾小管上皮细胞、肾小球细胞和肾间质浸润的淋巴细胞HBVDNA阳性率分别为49．47％（47／95）、45．26％（43／95）和33．68％（32／95）;其中18例患者肾组织中HBVDNA同时定位于肾小管上皮细胞、肾小球系膜细胞和少数间质淋巴细胞的细胞核中。结论：除了HBV抗原、抗体复合物所致体液免疫损伤外,也要考虑肾组织直接感染HBV,并参与了IgA肾病的发病。     

不可分型流感嗜血杆菌的特性及抗原筛选研究进展

不可分型流感嗜血杆菌(nontaxable Haemophilus influenzae,NTHi)是一类没有荚膜的革兰阴性球杆菌,常寄居于人类上呼吸道,是重要的机会致病菌,能引起人类中耳炎、肺炎及反复发作的呼吸道感染等.目前还没有一种预防这种病原菌感染的疫苗,随着近几年抗生素的滥用,细菌的耐药性问题越发突出,这就使开发一种安全有效的疫苗显得尤为重要.此文对NTHi的致病性、菌株特点及其抗原筛选的研究进展作一概述.     

基因工程烟草花叶病毒在疫苗研发中的应用

烟草花叶病毒(tobacco mosaic virus,TMV)是一种能感染植物的RNA病毒.因其基因组较小,易于进行遗传操作,且感染过程简单,适于改造成微小颗粒,故近年来已广泛用于疫苗研发.此文对TMV多肽表达及抗原展示系统的应用、疫苗开发中TMV操作的最新进展以及疫苗在动物模型中诱导体液和细胞免疫应答做一综述.     

Dendritic cell-based immunogens for B-cell chronic lymphocytic leukemia

Hybrids generated from tumor cells and dendritic cells (DC) have been proposed as tools for treating malignant disease. Here, we study the underlying principles and the feasibility for the adjuvant therapy of human B cell chronic-lymphocytic leukemia (B-CLL). CLL cells and allogeneic DC were only mixed or additionally fused. Using a combination of FACS and fluorescence microscopic analyses, we show that DC-CLL hybrids can be successfully generated. However, fusion frequencies have to be critically evaluated because the number of fused cells is overestimated when based on FACS analyses alone. The capability of activating patients' PBMC was examined by measuring cytokine secretion in co-culture assays. We made a systematic comparison of the immunostimulatory capacities of different stimulator cell populations, including DC-CLL fusion samples, unfused mixtures of DC and CLL cells as well as DC or tumor cells alone. Surprisingly, even unfused mixtures had a pronounced tumor-directed immunostimulatory effect. This could be explained by the capture of antigens from surrounding leukemia cells by DC during co-cultivation. Although fusion frequencies were low, PBMC stimulation was significantly more effective when the mixtures were subjected to cell fusion. The most potent stimulus was provided by DC-CLL fusion samples derived from mature DC, probably due to their enhanced costimulatory capacity. In summary, DC-tumor cell hybrids might be feasible in the treatment of B-CLL. It should be considered that FACS analysis is not sufficient to assess fusion frequencies and that interactions between unfused DC and CLL cells also result in PBMC activation.     

利用小鼠感染模型筛选与鉴定幽门螺杆菌外膜蛋白抗原

目的:利用小鼠感染模型筛选与鉴定幽门螺杆菌SS1株的外膜蛋白抗原。方法:提取SS1株的外膜蛋白进行双向电泳,用幽门螺杆菌感染的小鼠血清作免疫印迹实验,将阳性反应蛋白点进行质谱鉴定分析,将肽质量指纹谱数据输入互联网上的蛋白质数据库进行检索。结果:获得32种抗原相关蛋白。通过与已有报道的幽门螺杆菌感染人抗原比较分析,发现大部分典型的保护性抗原在本实验中都可以检测到。结论:幽门螺杆菌感染的小鼠模型适用于人用保护性幽门螺杆菌抗原的筛选;而且此研究中得到的相关抗原蛋白对于寻找与鉴定幽门螺杆菌未知保护性抗原也有参考价值。     

Autophagy as an emerging dimension to adaptive and innate immunity

Autophagy is an evolutionary conserved cellular process during which cytoplasmic material is engulfed in double membrane vacuoles that then fuse with lysosomes, ultimately degrading their cargo. Emerging evidence, however, now suggests that autophagy can form part of our innate and adaptive immune defense programs. Recent studies have identified pattern recognition molecules as mediators of this process and shown that intracellular pathogens can interact with and even manipulate autophagy. Recent translational evidence has also implicated autophagy in the pathogenesis of several immune-mediated diseases, including Crohn disease. In this review, we present autophagy in the context of its role as an immune system component and effector and speculate on imminent and future research directions in this field.     

3种抗原修复法对免疫组化结果的影响

目的采用微波加热、高温加热和酶消化进行组织抗原修复的免疫组织化学技术，比较三种抗原修复方法暴露抗原之间的区别，寻求最佳的免疫组化方法。方法微波修复组、高压加热组和酶消化组，各组用Envision试剂盒，检测Ki-67、CDla、CD83、CD3、CD4、CD8、CD45RO染色结果。结果三种抗原修复方法有明显差异，高压加热最佳，微波加热其次，酶消化效果最差。结论高压加热组织抗原修复方法经济、操作简单，适合大量标本使用。