胶质母细胞瘤和胶质瘤干细胞

胶质母细胞瘤（GBM）是一种高度恶性、浸润性、异质性和致命性的脑肿瘤,虽然其治疗方法不断改进,但GBM患者的预后依然很差。近年来,肿瘤干细胞学说的提出为肿瘤的产生和治疗提供了新的思路。自脑肿瘤中分离出一群具有自我更新、增殖和神经分化等干细胞特性的肿瘤细胞以来,这群肿瘤干细胞使得GBM的研究也越来越广泛和深入。本文就GBM和胶质瘤干细胞的最新相关进展进行综述。     

不同分子分型胶质母细胞瘤中NTSR1的表达及意义

目的 探讨胶质母细胞瘤(glioblastoma,GBM)的分子分型特征、NTSR1的表达及其对预后的影响.方法 收集138例GBM的临床病理资料,采用免疫组化EnVision两步法检测NTSR1、IDH1、ATRX、p53、EGFR、PTEN、CD44、CHI3L1、vimentin表达.根据IDH1、EGFR、PT...     

cIMPACT-NOW对胶质瘤分子分型的补充更新及意义

中枢神经系统肿瘤分类分子信息及实践方法联盟-非WHO官方组织(cIMPACT-NOW)就2016 WHO中枢神经系统肿瘤分类第4版修订版发布以来的神经系统肿瘤部分临床实践中的分类分级、争议问题与研究进展进行了深入的分析研究, 发布了4次更新, 包括(1)NEC、NOS术语的使用范围;(2)H3K27M突变型弥漫性中线胶质瘤的定义修订;(3)IDH野生型具有胶质母细胞瘤分子特征的弥漫性星形细胞胶质瘤, WHO Ⅳ级的分子遗传特征;(4)以MYB、MYBL1或FGFR1改变或BRAF V600E突变为特征的IDH野生型/H3野生型弥漫性胶质瘤。上述更新将成为未来第5版WHO中枢神经系统肿瘤分类改版建议, 在该文中逐一进行分析解读。     

肿瘤的分子分型与分子靶向治疗

疾病的分子分型（molecular classification）是通过综合的分子分析技术为疾病分类提供更多的信息，从而使疾病分类的基础从宏观形态学转向以分子特征为基础的新的分类体系（molecular characteristics-based classification）。目前可以在DNA、RNA和蛋白质水平上进行疾病分子分型研究，在DNA水平可以依据基因突变或多态性、基因组的细胞遗传学改变或甲基化差异进行分型。     

胶质瘤中失调的microRNA及相关基因研究进展

胶质瘤是一种常见的脑肿瘤,发生于神经外胚层。按细胞种类分,胶质瘤的主要类型有星形胶质细胞瘤、少突胶质细胞瘤和胶质母细胞瘤。2007年,世界卫生组织按胶质瘤的恶性程度和预后的好     

脑节细胞性胶质瘤的分子遗传学研究

目的通过研究脑节细胞性胶质瘤全基因组的遗传学改变,探讨该肿瘤的发病机制。方法应用比较基因组杂交技术,分析脑节细胞性胶质瘤全基因组的遗传学改变。结果收集脑节细胞性胶质瘤5例,男性3例,女性2例。其中,3例肿瘤发现有9号染色体短臂(9p)的丢失,2例有7号染色体的获得,该结果通过荧光原位杂交(FISH)技术得到了进一步的证实。应用免疫组织化学(ABC法)染色,位于染色体7p11-p13上的癌基因表皮生长因子受体(EGFR)在所有5例节细胞性胶质瘤中都无异常表达。此外,在染色体2q33-q34,8q12-q22,14q21-qter,15q26-citer和Y上也都发现了遗传物质的丢失或扩增。结论染色体9p的丢失及7号染色体的获得可能与脑节细胞性胶质瘤的发病机制有关。     

基于Hurst指数的脑胶质瘤分级方法

目的基于复杂度分析对胶质瘤患者的磁共振大脑静息态数据进行描述,寻找基于复杂度分析的肿瘤分级的客观指标。方法基于复杂度赫斯特(Hurst)指数分析方法对被试者大脑肿瘤fMRI影像的功能信息进行提取和分析,并对肿瘤进行分级研究。首先基于MRIcro软件对患者肿瘤区域、对侧正常区域以及正常对照组的肿瘤对应区域进行提取;接着对提取出来的区域进行Hurst指数计算;然后对肿瘤区域及其对侧正常区域的Hurst指数值进行统计分析,对肿瘤区域及对照组同区域的Hurst指数值进行统计分析;最后将29例肿瘤患者样本按照病理等级进行分组,其中一级肿瘤患者10例,二级肿瘤患者7例,三、四级肿瘤患者各6例,对不同组别的Hurst指数进行双样本统计分析。结果被试肿瘤区域的Hurst指数值与肿瘤等级成正比关系,肿瘤等级越高Hurst指数值越大。统计分析表明不同级别肿瘤区域的Hurst指数差异具有统计学意义。低级别肿瘤Hurst指数范围为0.6381~0.6737,高级别肿瘤Hurst指数范围为0.7514~0.8194。结论Hurst指数分析方法可以区分低级别和高级别胶质瘤,可以为更细致的胶质瘤的等级划分提供帮助。     

MHCⅡ类分子在CNS胶质细胞上的表达

本文简要介绍了MHCⅡ类分子表达的调控机制 ,MHCⅡ类分子及其协同刺激因子在CNS中的小胶质细胞及星形胶质细胞上的表达及其在多发性硬化发病过程中所起的作用。     

胶质瘤细胞增殖及凋亡调控紊乱研究的进展

胶质瘤占原发性脑肿瘤的60％～70％,且多数呈浸润性生长,手术不易全切。化疗和放疗既不能高度特异地杀伤胶质瘤细胞,又可能产生中枢神经系统,乃至全身不能耐受的毒副作用,治疗效果差。在全身肿瘤中,恶性胶质瘤5年病死率仅次于胰腺癌和肺癌居第3位,5年生存率不足5％。近20年中,胶质瘤的疗效和患者预后没有明显改善。     

xCT和促血管生成因子在胶质瘤组织中肿瘤相关巨噬细胞的表达及意义

目的：探讨xCT和促血管生成因子在胶质瘤组织中肿瘤相关巨噬细胞（TAMs）中的表达,以及TAMs对胶质瘤进展的影响。方法：分离并培养人新鲜胶质瘤和正常脑组织中的TAMs。采用荧光实时定量（RT-PCR）技术检测M2表型标记物CD14和CD86,促血管生成因子Arg-1和CD209,以及 xCT-mRNA表达水平。组织冰冻切片免疫荧光染色检测CD68和xCT在胶质瘤中的表达。结果：xCT和CD68在胶质母细胞瘤(WHO°Ⅳ)中的表达明显高于WHO°Ⅱ胶质瘤和正常脑组织,且xCT和CD68共同表达于小胶质细胞中。xCT mRNA在分化程度差的胶质瘤中表达明显增高。此外,小胶质细胞M2表型标记物表达水平(CD14和CD86)、活化状态的TAMs数目和促血管生成因子(Arg-1和CD209)与肿瘤分级相关。结论：TAMs能够通过xCT过表达,促炎症因子和促血管生成因子促进胶质瘤的发展。肿瘤中M2表型的TAMs募集与脑胶质瘤的不良预后相关。     

Pathology and molecular genetics of astrocytic gliomas

Astrocytic gliomas are the most common primary brain tumours. Here we summarize the characteristic neuropathological features of the different types of astrocytic neoplasms according to the World Health Organization classification of tumours of the nervous system. In addition, we report on the present state of the art concerning the molecular genetics of these tumours. Over the past 20 years a number of recurrent chromosomal, genetic and epigenetic alterations have been found to be associated with the different histological types and malignancy grades of astrocytic tumours. However, we are still far from understanding the complex mechanisms that underly tumour initiation and progression in the individual case. Furthermore, the clinical significance of molecular parameters for the diagnostic and prognostic assessment of astrocytic gliomas is still limited. Therefore further investigation of the molecular mechanisms underlying oncogenesis and progression of these most common brain tumours is necessary to improve their diagnostic assessment and to devise novel, individually tailored treatment strategies.     

Immunohistochemical and molecular updates in cutaneous soft tissue neoplasms

Accurate classification of soft tissue neoplasms of the skin and subcutis can be challenging given the sometimes significant histomorphologic and immunohistochemical overlap between the entities that comprise this ever-expanding category of tumors. With the benefit of continually emerging adjuncts to histologic diagnosis, pathologists have a number of tools at their disposal for navigating this group of neoplasms. This article aims to review recent immunohistochemical and molecular updates in the diagnosis of cutaneous soft tissue neoplasms.     

蜡样芽胞杆菌DNA分子分型研究

目的 建立蜡样芽胞杆菌分子分型方法，用于蜡样芽胞杆菌食物中毒的快速溯源。方法15株蜡样芽胞杆菌进行生化分型，同时进行vrrA基因PCR扩增和聚丙烯酰胺凝胶电泳-银染检测PCR扩增产物，所有PCR扩增产物进行序列分析，并用ClustalW(ebi．ac．uk)分析软件对DNA序列进行同源性比较。结果传统生化分型：15株蜡样芽胞杆菌中12株可分为3个型，3株不能分型；主要生化型为1型、2型和4型。分子分型：15株蜡样芽胞杆菌都可分为7个型。结论、vrrA基因可作为蜡样芽胞杆菌分子分型的一个多态性遗传标记。蜡样芽胞杆菌分子分型方法与传统生化分型方法相比，将传统生化分型所需的48h甚至更长时间缩短到5h，具有简便快速准确的优点，可做到快速溯源。     

Gastroenteropancreatic neuroendocrine neoplasms: selected pathology review and molecular updates

Gastroenteropancreatic (GEP) neuroendocrine neoplasms can be broadly separated into well‐ and poorly differentiated categories. Tumours within each category have similarities in morphology and immunophenotype, but vary in grade, behaviour, molecular signature and responses to therapy. The aetiology of these differences is multifactorial. Site of origin, mucosal milieu and hereditary influences are some of the currently known factors. Given these differences, staging and grading systems continue to evolve, and the most recent World Health Organization classification of pancreatic neuroendocrine neoplasms reflects this by introducing a grade 3 neuroendocrine tumour category for morphologically well‐differentiated tumours with an elevated Ki‐67 proliferation index and/or mitotic count. This review aims to highlight current classification guidelines with discussion of unique site‐specific features of selected GEP neuroendocrine neoplasms and an emphasis on practical issues related to daily reporting.     

Angiogenesis in gliomas: biology and molecular pathophysiology

Glioblastoma multiforme (GBM) is characterized by exuberant angiogenesis, a key event in tumor growth and progression. The pathologic mechanisms driving this change and the biological behavior of gliomas remain unclear. One mechanism may involve cooption of native blood vessels by glioma cells inducing expression of angiopoietin-2 by endothelial cells. Subsequently, vascular apoptosis and involution leads to necrosis and hypoxia. This in turn induces angiogenesis that is associated with expression of hypoxia-inducible factor (HIF)-1alpha and vascular endothelial growth factor (VEGF) in perinecrotic pseudopalisading glioma cells. Here we review the molecular and cellular mechanisms implicated in HIF-1-dependent and HIF-1-independent glioma-associated angiogenesis. In GBMs, both tumor hypoxia and genetic alterations commonly occur and act together to induce the expression of HIF-1. The angiogenic response of the tumor to HIF-1 is mediated by HIF-1-regulated target genes leading to the upregulation of several proangiogenic factors such as VEGF and other adaptive response molecules. Understanding the roles of these regulatory processes in tumor neovascularization, tumor growth and progression, and resistance to therapy will ultimately lead to the development of improved antiangiogenic therapies for GBMs.     

Recent advances upper gastrointestinal lymphomas: molecular updates and diagnostic implications

Approximately one‐third of extranodal non‐Hodgkin lymphomas involve the gastrointestinal (GI) tract, with the vast majority being diagnosed in the stomach, duodenum, or proximal small intestine. A few entities, especially diffuse large B‐cell lymphoma and extranodal marginal zone lymphoma of mucosa‐associated lymphoid tissue, represent the majority of cases. In addition, there are diseases specific to or characteristic of the GI tract, and any type of systemic lymphoma can present in or disseminate to these organs. The recent advances in the genetic and molecular characterisation of lymphoid neoplasms have translated into notable changes in the classification of primary GI T‐cell neoplasms and the recommended diagnostic approach to aggressive B‐cell tumours. In many instances, diagnoses rely on morphology and immunophenotype, but there is an increasing need to incorporate molecular genetic markers. Moreover, it is also important to take into consideration the endoscopic and clinical presentations. This review gives an update on the most recent developments in the pathology and molecular pathology of upper GI lymphoproliferative diseases.     

Serological and molecular typing in platelet alloantibody investigations

Alloimmunization against platelet antigens causes complications in transfusion settings as platelet transfusion refractoriness and post‐transfusion purpura, as well as in pregnancy, causing fetal/neonatal alloimmune thrombocytopenia. Strategies for the laboratory investigations depend on a repertoire of serological and molecular assays and are often dependent on timing and objective. Technical improvements have led to a number of sophisticated methods for alloantigen typing and alloantibody identifications during the last decade; however, some traditional methods are still beneficial. The laboratory investigations should ensure that the causative antibody specificities are identified as soon as possible to support the correct diagnosis and guide the selection of compatible platelets if needed.     

食物中毒中分离的副溶血性弧菌的分子分型研究

目的运用脉冲场凝胶电泳（PFGE）技术研究深圳市罗湖区2005-2007年食物中毒事件中分离获得的49株副溶血性弧菌的分子流行情况。方法样品采用荧光PCR与传统分离培养同时检测,对分离获得的副溶血性弧菌阳性菌株进行脉冲场凝胶电泳（PFGE）,BioNumerics软件对图谱进行聚类分析。结果 49株副溶血性弧菌中,有12株不能分型,其余36株副溶血性弧菌分离株大致可分为Ⅰ、Ⅱ、Ⅲ3个群,相同血清型的菌株其PFGE型大致相同,同一起食物中毒的菌株间有较高的相关性。结论罗湖区副溶血性弧菌食物中毒存在流行克隆株,PFGE分子分型技术在食物中毒追踪溯源方面有重要提示性作用。