颅咽管瘤中BCL-2蛋白的表达及意义

目的　分析颅咽管瘤中凋亡抑制基因BCL - 2在蛋白水平的表达 ,探讨其在颅咽管瘤生长机制中的意义。方法　选取经手术及病理证实的颅咽管瘤 4 9例 ,采用免疫组化法检测BCL 2蛋白的表达。结果　BCL 2的阳性表达程度在不同病理类型的颅咽管瘤上有显著差异 ,造釉细胞型颅咽管瘤的表达强度显著高于鳞状乳头型颅咽管瘤 (P <0 0 1)。结论　BCL 2在不同病理类型的颅咽管瘤中的表达呈现明显的区别 ,提示 :凋亡调控机制的失控可能是造釉型颅咽管瘤生长的重要机制之一 ;胚胎残余组织的继续增殖学说更能解释造釉细胞型颅咽管瘤的起源可能。     

趋化因子CXCL12及其受体CXCR4与造釉型颅咽管瘤侵袭、复发的相关性研究

目的探讨趋化因子及其受体(CXCL12/CXCR4)在造釉细胞型颅咽管瘤中的表达并分析其与肿瘤侵袭、复发的相关性。方法应用免疫组化法和western blot方法对20例造釉细胞型颅咽管瘤标本(原发组11例,复发组9例)中CXCL12/CXCR4的表达进行检测。结果 CXCL12/CXCR4在复发组造釉细胞型颅咽管瘤中的阳性表达明显高于原发组(P<0.05)。结论 CXCL12/CXCR4可能在造釉细胞型颅咽管瘤侵袭、复发过程中起重要的作用。CXCL12/CXCR4可能成为评价造釉细胞型颅咽管瘤侵袭性生长和复发的标记物。     

miR-200家族及侵袭相关基因ZEB1、ZEB2和CTNNB1在颅咽管瘤组织中的表达及意义

目的 检测miR-200家族及侵袭相关基因ZEB1、ZEB2和CTNNB1在颅咽管瘤组织中的表达并初步探讨其在颅咽管瘤侵袭性生长中的作用.方法 收集四川大学华西医院自2017年6月-2018年12月经手术切除的造釉细胞型颅咽管瘤(ACP)30例和鳞状上皮乳头型颅咽管瘤(PCP)30例的新鲜标本,手术切除的失活脑组织作为...     

炎症相关因子IFN-α及TGF-β1在颅咽管瘤的表达及意义

目的探讨炎症相关因子IFN-α、TGF-β1与颅咽管瘤炎症反应的关系。方法采用免疫组化GTVisionTM法检测α-干扰素(interferon-α,IFN-α)、转化生长因子-β1(transforming growth factorβ1,TGF-β1)在58例颅咽管瘤组织中的表达情况,比较不同病理类型颅咽管瘤、复发组及初发组颅咽管瘤组织中IFN-α、TGF-β1的表达水平。结果造釉细胞型及复发颅咽管瘤IFN-α表达广泛。44例造釉细胞型颅咽管瘤有40例IFN-α表达阳性(90.91%),鳞状乳头型14例中有12例表达阳性,造釉细胞型IFN-α阳性表达率明显高于鳞状乳头型(Z=-2.003,P<0.05)。16例复发颅咽管瘤均有IFN-α阳性表达,阳性表达率高于初发组(Z=-2.085,P<0.05)。TGF-β1在鳞状乳头型颅咽管瘤明显表达,14例中有10例阳性表达,而造釉细胞型44例仅有14例表达阳性(Z=-2.129,P<0.05)。经Spearman相关分析,在全部颅咽管瘤中,IFN-α与TGF-β1表达程度呈负相关(rs=-0.273,P<0.05)。结论颅咽管瘤存在复杂的炎症反应,炎症相关因子IFN-α、TGF-β1可能参与颅咽管瘤细胞的生长调控,两者之间可能存在拮抗作用。     

颅咽管瘤β-连接素表达及其基因突变分析

目的分析不同病理类型颅咽管瘤的β-连接素表达特征及基因外显子3突变的意义。方法研究我院自2004年1月至2006年1月共23例颅咽管瘤标本,其中造釉细胞型颅咽管瘤20例、鳞状乳头型3例,应用免疫组化方法检测β-连接素表达特征,同时分析其基因外显子3的突变情况。结果免疫组化结果显示,β-连接素在造釉细胞瘤型颅咽管瘤的细胞核及细胞浆中表达,而在鳞状乳头型颅咽管瘤中仅见细胞膜表达;基因突变分析显示,40%的造釉细胞型颅咽管瘤β-连接素基因在外显子3上发生突变,鳞状乳头型无此突变。结论造釉细胞型颅咽管瘤和鳞状乳头型颅咽管瘤不仅在临床病理上,而且在分子水平也存在差异。β-连接素基因外显子3的突变在造釉细胞型颅咽管瘤的发生、发展中可能起一定作用。     

SYBR荧光实时定量PCR检测不同病理类型颅咽管瘤ICAM-1 mRNA表达

目的定量研究细胞间粘附分子基因(ICAM—1 mRNA)在不同病理类型颅咽管瘤的表达差异及意义。方法收集30例经手术治疗的颅咽管瘤标本,采用SYBR荧光实时定量PCR法检测 ICAM-1 mRNA在肿瘤组织的表达,并对表达结果行统计学分析。结果造釉细胞型颅咽管瘤 ICAM-1mRNA表达量为(62．18±6．43)×103 copies／μg,鳞状乳头型颅咽管瘤ICAM-1 mRNA表达量为 (1．13±0．17)×103 copies／μg,造釉细胞型颅咽管瘤ICAM-1 mRNA表达量显著性高于鳞状乳头型颅咽管瘤(P<0．01)。结论两种病理类型颅咽管瘤ICAM—1 mRNA表达存在显著性差异,此差异性可能与两种病理类型颅咽管瘤不同的肿瘤炎症有关。     

uPA和VEGF与儿童造釉细胞型颅咽管瘤复发的相关性研究

目的 探讨尿激酶型纤溶酶原激活物(uPA)和血管内皮生长因子(VEGF)表达与造釉细胞型颅咽管瘤复发的关系.方法 应用免疫组化检测48例造釉细胞型颅咽管瘤标本(原发组28例,复发组20例)中uPA和VEGF的表达.结果 造釉细胞型颅咽管瘤中,uPA在复发组的总阳性表达率95.0％,明显高于原发组的42.9％(Z=-3.396,P＜0.05);VEGF在复发组的总阳性表达率90.0％,明显高于原发组的64.3％(Z=-2.909,P＜0.05).复发组造釉细胞型颅咽管瘤中uPA与VEGF表达呈正相关(r=0.534,P＜0.05),原发组造釉细胞型颅咽管瘤中uPA与VEGF表达无明显相关性(r=-0.105,P＞0.05).结论 高水平的uPA和VEGF能协同促进细胞外基质的降解和血管生成的,促进肿瘤的复发转移,可以作为儿童造釉细胞型颅咽管瘤重要的生物学行为预测和预后指标.     

CD147、MMP-9与釉质型颅咽管瘤侵袭性生长及复发的相关性研究

目的:探讨细胞外基质金属蛋白酶诱导剂( CD147,EMMPRIN)和基质金属蛋白酶-9(MMP-9)在釉质型颅咽管瘤中的表达及其与肿瘤侵袭、复发的相关性。方法:应用免疫组化法对40例釉质型颅咽管瘤标本（原发组24例,复发组16例）中CD147和MMP-9的表达进行检测。结果:CD147在复发组釉质型颅咽管瘤中的总阳性表达率87.5％,明显高于原发组总阳性率37.5％ (P＜0.05);MMP-9在复发组釉质型颅咽管瘤中的总阳性表达率93.7％,明显高于原发组总阳性率41.7％ (P ＜0.05)。复发组釉质型颅咽管瘤中CD147与MMP-9表达呈正相关（P＜0.01）,原发组釉质型颅咽管瘤中CD147与MMP-9表达无明显相关性。结论: CD147与MMP-9可能在釉质型颅咽管瘤侵袭生长和肿瘤复发过程之中扮演着重要的角色,CD147与MMP-9可能成为评价釉质型颅咽管瘤侵袭性生长和复发倾向的重要参考指标。     

不同类型颅咽管瘤的组织炎症和细胞增殖性

目的研究不同病理类型颅咽管瘤的组织炎症及细胞增殖性对预后的影响.方法对30例经手术切除的颅咽管瘤组织采用免疫组织化学SP法检测白细胞共同抗原CD45和细胞周期相关核抗原Ki-67的抗体MIB-1的表达,分别计算CD45标记指数(CD45 LI)和MIB-1标记指数(MIB-1 LI).结果CD45标记的炎症反应在颅咽管瘤组织中广泛存在,MIB-1主要在颅咽管瘤基底细胞层表达.造釉细胞型颅咽管瘤组织CD45 LI(32.4%±15.0%)及细胞MIB-1 LI(18.2%±8.7%)显著性高于鳞状乳头型颅咽管瘤(分别为13.6±7.6%、7.1%±4.9%,P＜0.05).结论颅咽管瘤造釉细胞性较鳞状乳头型具有更强的组织炎症和细胞增殖性,可能是影响其预后的原因.     

造釉细胞型颅咽管瘤细胞体外培养与检测

目的 探讨有效的实体性造釉细胞型颅咽管瘤细胞原代培养方法,检测体外培养的颅咽管瘤细胞生物学特性.方法 采用胰酶消化法建立实体性颅咽管瘤细胞株,并通过滤膜过滤纯化细胞；倒置显微镜、HE染色观察生长情况及细胞形态,免疫组化证实其细胞来源,噻唑蓝比色(MTT)法绘制细胞生长曲线,并用流式细胞仪分析细胞周期.结果 肿瘤呈典型上皮样形态,免疫细胞鉴定颅咽管瘤细胞原代培养成功,肿瘤细胞增殖速度缓慢,且均为二倍体细胞.结论 造釉细胞型颅咽管瘤细胞通过酶消化及改良的血清培养基法成功建立,且滤膜过滤可以提高所培养细胞的纯度和成功率.     

2-DPMP (desoxypipradrol, 2-benzhydrylpiperidine, 2-phenylmethylpiperidine) and D2PM (diphenyl-2-pyrrolidin-2-yl-methanol,diphenylprolinol): A preliminary review

2-DPMP (desoxypipradrol, 2-benzhydrylpiperidine, 2-phenylmethylpiperidine) and D2PM (diphenyl-2-pyrrolidin-2-yl-methanol, diphenylprolinol) are psychoactive substances, sold primarily over the Internet and in ‘head’ shops as ‘legal highs’, ‘research chemicals’ or ‘plant food’. Originally developed in the 1950s for the treatment of narcolepsy and ADHD, 2-DPMP's use soon became very limited. Recreational use of 2-DPMP and D2PM appears to have started in March 2007, but only developed slowly. However, in the UK their popularity grew in 2009, increasing rapidly during summer 2010. At this time, there were many presentations to UK Emergency Departments by patients complaining of undesirable physical and psychiatric effects after taking 2-DPMP. In spring 2011 there were similar presentations for D2PM. Recreational use of these drugs has been reported only occasionally in on-line user fora. There is little scientifically-based literature on the pharmacological, physiological, psychopharmacological, toxicological and epidemiological characteristics of these drugs. Here we describe what is known about them, especially on their toxicity, including what we believe to be the first three deaths involving the use of 2-DPMP in August 2010. There are no international controls imposed on 2-DPMP or D2PM. However, a ban on their UK importation was imposed in November 2011 and they became Class C drugs on 13 June 2012. It is critical that any other cases, including non-fatal overdoses, are documented so that a scientific evidence-base can be established for them.     

Spinocerebellar ataxia 2 (SCA2)

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominantly inherited, neurodegenerative disease. It can manifest either with a cerebellar syndrome or as Parkinson’s syndrome, while later stages involve mainly brainstem, spinal cord and thalamus. This particular atrophy pattern resembles sporadic multi-system-atrophy (MSA) and results in some clinical features indicative of SCA2, such as early saccade slowing, early hyporeflexia, severe tremor of postural or action type, and early myoclonus. For treatment, levodopa is temporarily useful for rigidity/bradykinesia and for tremor, magnesium for muscle cramps, but neuroprotective therapy will depend on the elucidation of pathogenesis. The disease cause lies in the polyglutamine domain of the protein ataxin-2, which can expand in families over successive generations resulting in earlier onset age and faster progression. Genetic testing in SCA2 and other polyglutamine disorders like the well-studied Huntington’s disease is now readily available for family planning. Although these disorders differ clinically and in the affected neuron populations, it is not understood how the different polyglutamine proteins mediate such tissue specificity. The neuronal intranuclear inclusion bodies described in other polyglutamine disorders are not frequent in SCA2. For the quite ubiquitously expressed ataxin-2, a subcellular localization at the Golgi, the endoplasmic reticulum and the plasma membrane, in interaction with proteins of mRNA translation and of endocytosis have been observed. As a first victim of SCA2 degeneration, cerebellar Purkinje neurons may be preferentially susceptible to alterations of these subcellular pathways, and therefore our review aims to portray the particular profile of the SCA2 disease process and correlate it to the specific features of ataxin-2.     

Neurofibromatosis 2

PURPOSE OF REVIEW: Recent clinical and molecular research on neurofibromatosis 2 (NF2) is reviewed, and the implications for clinical practice and research are discussed. RECENT FINDINGS: NF2 patients who are treated in specialty centers have a significantly lower risk of mortality than those who are treated in non-specialty centers. Vestibular schwannoma growth rates in NF2 are generally higher in younger people but are highly variable, even among multiple NF2 patients of similar ages in the same family. Radiation therapy is best reserved for NF2 patients who have particularly aggressive tumors, those who are poor surgical risks, those who refuse surgery, or those who are elderly. In-vivo studies have demonstrated that leptomeningeal cell activation of in mice results in leptomeningeal hyperplasia and meningioma formation. In-vitro studies have identified molecules that interact with the product (merlin or schwannomin), some of which (e.g., CD44 and paxillin) may play critical roles in merlin growth regulation. SUMMARY: NF2 patients should be referred to specialty treatment centers for optimal care. Clinical management of multiple patients in NF2 families cannot be based on the expectation of similar vestibular schwannoma growth rates, even when other clinical aspects of disease severity are similar. The availability of accurate mouse models of human NF2-associated tumors and the identification of molecules involved in merlin growth regulation now provide an opportunity to design targeted treatments for schwannomas and meningiomas.