颅咽管瘤中基质金属蛋白酶MMP-2的表达及意义

目的探讨颅咽管瘤局部侵袭性生长的生物学机制。方法使用免疫组织化学S-P法检测基质金属蛋白酶MMP-2在14例颅咽管瘤细胞中的表达。结果2例乳头型、9例造釉细胞型及1例混合型颅咽管瘤均有不同程度的表达。MMP-2阳性染色主要位于肿瘤细胞的胞质中,尤其以鳞状上皮的棘细胞和造釉上皮的近基底层细胞的表达最为明显。1例囊状复发及1例γ-刀术后造釉细胞瘤型未见表达。结论3种类型颅咽管瘤细胞均能产生MMP-2,提示MMP-2可能是颅咽管瘤局部侵袭的机制之一。     

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。     

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。     

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。     

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。     

凋亡相关基因Bcl-2、Bax在颅咽管瘤发病机制中的意义

目的 探讨颅咽管瘤发生发展中可能存在的凋亡调控机制。方法 采用免疫组化技术，对50例颅咽管瘤肿瘤组织中bcl-2、Bax基因的表达进行检测，计算bcl-2／Bax比值。结果①bcl-2在颅咽管瘤肿瘤组织中过度表达，但在鳞状乳头型颅咽管瘤中的bcl-2阳性表达率及表达强度弱于釉质上皮型颅咽管瘤（P〈0．05）；Bax在颅咽管瘤肿瘤组织中不表达或弱阳性表达。②釉质上皮型颅咽管瘤中bcl-2／Bax比值明显高于鳞状乳头型颅咽管瘤（P〈0．05）。结论 凋亡抑制基因bcl-2的过度表达及凋亡促进基因Bax的表达减少导致的bcl-2／Bax比值增大，凋亡减少，细胞生存期延长可能是釉质上皮型颅咽管瘤发生发展的机理之一。     

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.     

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.     

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...     

颅咽管瘤中β-catenin基因的表达及临床意义

目的探讨β-catenin基因和颅咽管瘤病理类型及预后的关系。方法用免疫组化技术检测β-catenin基因在50例颅咽管瘤细胞和20例正常脑组织标本中的表达。结果颅咽管瘤组织中β-catenin蛋白的异常表达率高于正常对照组（P〈0．05），釉质上皮型颅咽管瘤组织中β-catenin蛋白的异常表达率高于鳞状乳头型颅咽管瘤（P〈0．05），颅咽管瘤复发者β-catenin蛋白的异常表达率高于非复发者（P〈0．05）。结论β-catenin基因的异常表达激活的异常Wnt通路改变可能在釉质上皮型颅咽管瘤的发生中起重要作用，同时颅咽管瘤细胞中β-catenin基因的异常表达，增加了肿瘤细胞的侵袭能力，使肿瘤的复发率增高。     

胰岛素对局灶性脑缺血再灌注大鼠c—fos和bcl—2基因表达的影响

目的探讨胰岛素对脑缺血再灌注损伤的中枢保护机制.方法参照ZeaLonga线栓法建立大鼠局灶性脑缺血再灌注模型,采用免疫组化法检测同一剂量胰岛素(2IU/kg)对缺血再灌注不同时限点脑组织FOS和BCL-2蛋白的表达.结果与假手术对照组和未用药组相比,胰岛素能显著上调缺血侧大脑皮层及基底节区FOS和BCL-2蛋白的表达(P<0.001).结论胰岛素能促进缺血再灌注脑组织FOS和BCL-2蛋白的表达,这可能是其中枢保护机制之一.     

颅咽管瘤钙化程度与骨桥蛋白的关系

目的通过检测颅咽管瘤组织中骨桥蛋白(OPN)的表达量来分析OPN与颅咽管瘤钙化的关系。方法收集本单位自2004年5月至2006年3月手术的颅咽管瘤标本共54例,根据术中所见及影像学结果分析钙化程度,采用HE染色分析组织类型,免疫组化SP法检测OPN的表达情况;结合临床资料分析钙化程度与OPN表达强度的关系。结果肿瘤分两种类型即成釉细胞型(41例),鳞状细胞型(13例)。经Mann-WhitneyU检验分析,OPN表达程度在成釉细胞型与鳞状细胞型之间存在显著性差异(Z=-4.813,P<0.001),成釉细胞型颅咽管瘤的表达显著高于鳞状细胞型颅咽管瘤。经Spearman相关分析,在成釉细胞型中随着钙化程度的增加,OPN表达程度显著增强(rs=0.533,P<0.01)。结论OPN与颅咽管瘤的钙化密切相关,推测是影响颅咽管瘤钙化程度的重要因素。     

BCL-XL expression levels influence differential regional astrocytic susceptibility to 1,3-dinitrobenzene

The selective vulnerability of brainstem astrocytes to 1,3-dinitrobenzene is mediated by a 10-fold lower threshold for opening of the cyclosporin A-inhibitable mitochondrial permeability transition pore (mtPTP). BCL-XL, BAX and BCL-2 are members of the BCL-2 protein family known to regulate both apoptotic and necrotic cell death signaling at the mtPTP. The levels at which these proteins are expressed relative to one another, where in the cell they are located and whether they are post-translational modified contributes greatly to the balance in active agonistic to active antagonistic BCL-2 proteins, and this critical balance has been hypothesized to dictate regional astrocytic susceptibility to DNB. The effects of DNB on the balance in expression of the BCL-2 family proteins have been evaluated in F344 rat DNB-sensitive (brainstem) and non-sensitive (cortical) tissue homogenates and primary astrocytes. No significant treatment-related alterations in BCL-XL, BAX or BCL-2 protein expression are observed in rat tissue homogenates or primary astrocytes. However, moderate increases in BCL-XL are observed only in DNB-treated rat cortical astrocytes, and these increases may be sufficient to shift the constitutive balance in expression of antagonistic to agonistic BCL-2 proteins from a ratio which favors BAX to one in which BAX and BCL-XL are comparably expressed. Rat primary brainstem and cortical astrocytes are also transiently transfected with bcl-xl to evaluate whether or not moderate enhancement of BCL-XL protein expression levels are sufficient to alter regional sensitivity to DNB in vitro. BCL-XL overexpression minimizes DNB-induced inhibition of succinate dehydrogenase (complex II) activity and increases significantly the concentration of DNB required to induce MPT onset in primary brainstem and cortical astrocytes. Results from the current investigation suggest that modest region-specific alterations in the balance in expression of antagonistic to agonistic BCL-2 proteins may adequately explain differential regional sensitivity to DNB-induced mitochondrial dysfunction.     

听神经瘤BCL-2蛋白及bcl-2/JH融合基因的研究

目的 评价石蜡包埋听神经瘤组织中ＢＣＬ－２蛋白表达及相关的ｂｃｌ－２（ｍｂｒ）／ＪＨ融合基因改变,以探讨ｂｃｌ－２癌基因在听神经瘤发病中的可能意义。方法 免疫组化检测石蜡包埋组织中ＢＣＬ－２蛋白的表达;提取石蜡包埋组织的ＤＮＡ,ＰＣＲ检测ｂｃｌ－２（ｍｂｒ）／ＪＨ融合基因。结果 本组４０例听神经瘤,ＢＣＬ－２蛋白表达阳性２７例（６７．５％）,ｂｃｌ－２（ｍｂｒ）／ＪＨ融合基因检出阳性１９例（４７．５％）．结论 听神经瘤中存在ＢＣＬ－２蛋白的高表达及ｔ（１４：１８）染色体易位,提示雪旺氏细胞凋亡抑制可能是听神经瘤发病的分子病理基础之一。     

bcl-2 protein expression in tumors of the central nervous system

bcl-2 protein (BCL-2) expression was immunohistochemically studied in 140 varied central nervous system tumors. The protein was most frequently expressed in neuronomas and ependymomas, and in normal ependymal cells and Schwann cells. Most pituitary adenomas could be classified into one of two subgroups, diffusely positive or diffusely negative tumors, while BCL-2 localized heterogeneously in normal pituitary glands. Although the protein was not detected in normal astrocytes, it was positive in reactive hypertrophic astrocytes observed in various pathological conditions. Similarly, astrocytic tumor cells often expressed BCL-2. Since lowgrade astrocytomas more often exhibited the protein than malignant gliomas, the degree of BCL-2 expression appeared to be related to the degree of malignancy of the gliomas. On the other hand, 7 out of 17 recurrent gliomas and medulloblastomas showed an increase in the frequency of protein expression compared with specimens from initial treatments. One recurrent astrocytic tumor which demonstrated anaplastic change showed a decrease in the frequency of BCL-2-positive cells. It is concluded that the frequency of BCL-2 expression in CNS tumors is increased when the non-neoplastic counterparts of the tumors exhibit the protein. Although it has been reported that overexpression of BCL-2 protects cells from damage by radiation and/or chemotherapy, we could not find any significant relationship between the degree of BCL-2 expression and the length of survival of patients with glioblastomas or medulloblastomas.     

颅咽管瘤钙化与CD44V6的关系

目的分析颅咽管瘤组织中CD44V6的表达与颅咽管瘤钙化的关系。方法收集2004年5月～2006年3月经手术治疗的颅咽管瘤标本54例。根据术中所见及影像学表现确定肿瘤钙化程度，采用苏木精一伊红染色分析肿瘤组织类型，免疫组化法检测CD44V6在肿瘤组织中的表达情况。结合临床资料分析钙化程度与CD44V6表达强度的关系。结果成釉细胞型颅咽管瘤41例，鳞状细胞型颅咽管瘤13例。经Mann—Whitney U检验分析，成釉细胞型颅咽管瘤CD44V6的表达显著高于鳞状细胞型颅咽管瘤（Z=-4．813，P〈0．001）。经Spearman相关分析，在成釉细胞型中随着钙化程度的增加，CD44V6表达程度显著增强（rs=0．527，P〈0．01）。结论CD44V6与颅咽管瘤的钙化密切相关，可能是影响其钙化程度的重要因素。     

Risperidone and haloperidol promote survival of stem cells in the rat hippocampus

Altered neuroplasticity contributes to the pathophysiology of schizophrenia. However, the idea that antipsychotics may act, at least in part, by normalizing neurogenesis has not been consistently supported. Our study seeks to determine whether hippocampal cell proliferation is altered in adult rats pretreated with ketamine, a validated model of schizophrenia, and whether chronic administration with neuroleptic drugs (haloperidol and risperidone) affect changes of cell genesis/survival. Ketamine per se has no effect on cell proliferation. Its withdrawal, however, significantly induced cell proliferation/survival in the hippocampus. Risperidone and haloperidol supported cell genesis/survival as well. During ketamine withdrawal, however, their application did not affect cell proliferation/survival additionally. TUNEL staining indicated a cell-protective potency of both neuroleptics with respect to a ketamine-induced cell death. As RT-PCR and Western blot revealed that the treatment effects of risperidone and haloperidol seemed to be mediated through activation of VEGF and MMP2. The mRNA expression of NGF, BDNF, and NT3 was unaffected. From the respective receptors, only TrkA was enhanced when ketamine withdrawal was combined with risperidone or haloperidol. Risperidone also induced BCL-2. Ketamine withdrawal has no effect on the expression of VEGF, MMP2, or BCL-2. It activated the expression of BDNF. This effect was normalized by risperidone or haloperidol. The findings indicate a promoting effect of risperidone and haloperidol on survival of young neurons in the hippocampus by enhancing the expression of the anti-apoptotic protein BCL-2 and by activation of VEGF/MMP2, whereby an interference with ketamine and thus a priority role of the NMDA system was not evident.     

核转录因子κB在颅咽管瘤炎症中的表达

目的探讨NF-κB与颅咽管瘤炎症反应的关系。方法免疫组化SP法检测核转录因子(nuclear factor-κB,NF-κB)的P65亚基、骨桥蛋白(osteopontin,OPN)在54例颅咽管瘤组织中的表达情况,以及炎症标志物C反应蛋白在成釉细胞型颅咽管瘤患者血清、脑脊液及肿瘤囊液中的检测结果,结合临床资料分析颅咽管瘤与炎症的关系。结果NF-κB(P65亚基)在成釉细胞型中过度表达,经Mann-Whitney U检验分析,成釉细胞型颅咽管瘤的表达显著高于鳞状细胞型颅咽管瘤(Z=-4.532,P0.001)。经Spearman相关分析,在成釉细胞型中NF-κB(P65亚基)与OPN表达程度呈正相关。C反应蛋白在成釉细胞型颅咽管瘤患者肿瘤囊液、脑脊液及血清中明显升高,分别为(4.28±0.90)mg/mL、(0.035±0.006)mg/mL、(1.72±0.54)mg/mL。结论炎症是颅咽管瘤与周围重要结构紧密粘连主要的影响因素,NF-κB与颅咽管瘤炎症的发生密切相关。