转化生长因子α及其受体在人脑星形细胞瘤中的表达及意义

目的　研究转化生长因子α(transforminggrowthfactoralpha ,TGF α)及其表皮生长因子受体 (epidermalgrowthfactorreceptor ,EGFR)在人脑星形细胞瘤中的表达及意义。方法　采用免疫组织化学方法检测 5 0例人脑星形细胞瘤标本和 10例正常人脑组织中TGF α和EGFR蛋白表达。结果　 5 0例人脑星形细胞瘤TGF α和EGFR蛋白表达总阳性率分别为 64 .0 % ( 3 2 /5 0 )和 68.0 % ( 3 4/5 0 ) ,正常脑组织未见阳性表达 (P <0 .0 1) ;二者密切相关 (P <0 .0 1) ,并与星形细胞瘤病理分级有显著相关性 ,其中Ⅰ～Ⅱ级者阳性率显著低于Ⅲ、Ⅳ级者 (P <0 .0 5 ) ;结论　TGF α和EGFR形成的自分泌环在人脑星形细胞瘤发生发展过程中起重要作用 ,同时检测它们可作为判断人脑星形细胞瘤临床分期、预后的重要指标     

人脑星形细胞瘤的CT和TEM联合研究

人脑星形细胞瘤的ＣＴ和ＴＥＭ联合研究图１星形细胞瘤（Ⅱ－Ⅲ级）。平扫显示左额额颞呈混杂密度病灶，形态不规则，病灶边缘不清楚、占位效应明显（↑）。图２与图１同一肿瘤的增强扫描，肿瘤呈现不规则，不均匀的增强。占位效应明显（↑）。图３星形细胞瘤（Ⅱ－Ⅲ级）...     

肝细胞生长因子及其受体mRNA在星形细胞瘤中的表达

目的　探讨肝细胞生长因子(HGF)及其受体(c Met)mRNA在正常脑组织和脑星形细胞瘤中的表达规律,探讨其与肿瘤增殖、肿瘤血管生成、临床病理及生存时间之间的关系。方法　用原位杂交法检测57例脑星形细胞瘤和5例正常脑组织标本HGF、c Met mRNA的表达;用免疫组织化学方法检测PCNA在肿瘤细胞中的表达,CD34 免疫组化反应检测并计算微血管密度(MVD),并结合临床病理资料进行分析。结果　在正常脑组织中未见HGF 和c Met 表达,而在脑星形细胞瘤中HGF、c Met、PCNA及CD34表达随病理级别的增高而明显增强(P<0.05),随生存期的延长而明显减弱(P<0.05),并且与患者的性别、年龄、肿瘤部位、肿瘤直径无关(P>0.05);HGF表达与c Met、PCNA的表达及MVD之间显著相关。结论　HGF/c Met在脑星形细胞瘤的形成与发展过程中起重要作用,它可促进肿瘤增殖及瘤组织内微血管的发生,并对预后判断有指导意义。     

转化生长因子与胶质细胞瘤

转化生长因子与胶质细胞瘤第四军医大学西京医院神经内科邓艳春综述粟秀初校转化生长因子（ＴＧＦｓ）是一组小分子多肽，１９７８年首次在Ｍｅｌｏｎｅｙ肉瘤转化的鼠３Ｔ３细胞条件培养基里被发现。经十余年的研究，人们对其性质、来源、分类及生物功能有了进一步的认识...     

脑星形细胞瘤VEGF-B、VEGF-C及MVD表达

[目的]分析血管内皮生长因子B(VEGF-B)、VEGF-C、微血管密度(MVD)与星形细胞瘤病理分级的关系,并对三者之间相关性进行探讨.[方法]应用免疫组化法检测73例不同级别人脑星形细胞瘤中VEGF-B、VEGF-C的表达水平和MVD.[结果]MVD随星形细胞瘤病理级别的增高而增加,差异均有显著性(P＜0.05);VEGF-B和VEGF-C的表达与病理级别无相关性.[结论]MVD可作为反映星形细胞瘤恶性程度的指标,星形细胞瘤的血管形成,可能除VEGF-B、VEGF-C外受多种血管生成因子的调控.     

伴严重瘤周脑水肿的脑膜瘤

目的 研究引起脑膜瘤瘤周严重脑水肿的原因及其与临床表现的关系。方法 通过分析患者的ＣＴ，ＭＲＩ，肿瘤部位及病恒亚型，并进行术后随访调查。结果 主要引流静脉或静脉窦附近的大中型脑膜瘤及病理为血管母细胞型脑膜瘤，血管内皮型脑膜瘤引起严重的瘤周脑水肿。结论脑膜瘤的部位，大小，分泌情况，性激素受体及是否影响静脉回流等因素都与瘤周脑水肿有关。     

脑星形细胞瘤近瘤周白质区的DTI征象及参数分析

[目的]应用磁共振弥散张量成像（DTI）技术探讨脑星形细胞瘤近瘤周白质区DTI征象,以及不同级别星形细胞瘤近瘤周区（IPR）平均弥散系数（MD）值、各向异性分数（FA）值改变的意义。[方法]48例脑星形细胞瘤术前行DTI扫描,重建FA图,评价FA图像中IPR的信号特点,并测定IPR及对侧正常脑白质区的MD值及FA值,计算相对MD（rMD）和相对FA值（rFA）。[结果]星形细胞瘤IPR白质区的FA图及彩色FA图能显示出白质纤维各向异性降低和走形方向的改变。星形细胞瘤IPR白质区MD值高于对侧正常脑白质组（t=11.423,P〈0.001）;除Ⅱ级与Ⅲ级星形细胞瘤组间MD值和rMD无统计学差异外,其余级别星形细胞瘤组间MD值和rMD均有统计学差异（P〈0.05）。星形细胞瘤IPR白质FA值低于对侧正常脑白质组（t=-22.611,P〈0.001）;Ⅲ~Ⅳ级星形细胞瘤IPR白质的FA值、rFA降低,明显低于Ⅰ~Ⅱ级星形细胞瘤组（P〈0.05）。[结论 ]FA图及彩色FA图能较为直观准确地反映IPR白质受肿瘤侵犯的情况;MD值、FA值能够一定程度定量反映不同级别星形细胞瘤对IPR造成的病理影响。     

人星形细胞瘤血管内皮生长因子表达

目的:探讨VEGF在星形细胞瘤中表达与星形细胞瘤组织学分级和患者年龄的关系.方法:应用免疫组化方法检测52例星形细胞瘤石蜡包埋病理切片.结果:VEGF在不同病理级别星形细胞瘤中表达程度不同,随组织级别增加,表达增强.VEGF高表达组患者平均年龄高于低表达组.结论:VEGF与星形细胞瘤生长及恶性进展关系密切,VEGF高表达与高龄有关,预示预后不良.     

脑膜瘤的病理学表现与瘤周脑水肿

为了解脑膜瘤的病理学改变与瘤周脑水肿的关系，我们对１３２例脑膜瘤病人的病理切片及２１例电镜检查结果进行了分析。结果发现：合体型、间变型及血管型脑膜瘤易伴重度瘤周水肿。瘤周水肿明显者，病理见肿瘤增殖活跃的表现。肉瘤型、间变型均见于中重度水肿组，非典型型重度水肿者显著高于良性型。若肿瘤血管成分增多，无砂粒体，可见血管外皮细胞易伴瘤周水肿。超微结构见水肿明显者，细胞核增大，核膜溶解，细胞内及细胞外水肿，线粒体溶解，粗面内质网扩张，溶酶体增多。中重度水肿者并可见分泌一排泄现象。     

脑膜瘤组织中NKCC-1和VEGF的表达与瘤周水肿的相关性研究

目的:探讨脑膜瘤组织中钠钾氯协同转运蛋白1(NKCC-1)和血管内皮生长因子(VEGF)的表达与脑膜瘤瘤周水肿(PTBE)之间的关系.方法:以2017年1月至2019年1月我院接收的108例脑膜瘤患者作为此次研究对象,运用相关检测方法了解其NKCC-1和VEGF水平,借助统计学软件分析其与脑膜瘤PTBE之间的关系.结果...     

血管内皮生长因子在脑膜瘤及瘤周脑组织中的表达

 目的　研究血管内皮生长因子（VEGF）在脑膜瘤瘤周水肿形成中的作用。方法　对经手术证实的幕上脑膜瘤37例患者共40个脑膜瘤进行研究,通过免疫组织化学法及Western blot检测肿瘤组织和瘤周脑组织中VEGF的蛋白表达,通过反转录PCR法检测VEGF的mRNA表达情况,以与β-actin的比值为其相对表达量;通过水肿指数（EI）评估术前瘤周水肿的严重程度,并分析其与VEGF表达的相关性。结果　在VEGF阳性病例中,VEGF蛋白水平在肿瘤组织、瘤周水肿脑组织和正常脑组织之间呈梯度降低（相对表达量分别为0.38±0.08、0.20±0.03、0.04±0.02）。在肿瘤组织中,VEGF的蛋白水平、RNA水平和EI呈正相关（r＝0.892、0.875,均P＜0.05）;在瘤周脑组织中,仅VEGF的蛋白水平和EI呈正相关（r＝0.912,P＜0.05）,而RNA则几乎未表达（0.06±0.02）。结论　VEGF在脑膜瘤瘤周水肿的形成过程中可能起着重要作用;VEGF可能是由肿瘤组织产生的,并扩散到瘤周脑组织中形成水肿。     

The relationship between peritumoral brain edema and the expression of vascular endothelial growth factor and its receptors in intracranial meningiomas

We examined the radiological and histological features of, and the influences of the expression of VEGF and its two major receptors, Flt-1 and Flk-1, on the development of peritumoral brain edema (PTBE) in patients with intracranial meningiomas. The expressions of VEGF and VEGF receptors in the immunohistochemical study were analyzed in relation to several factors, including tumor size, location, vascularity, and blood supply, as seen on digital subtraction angiographic studies. The edema volume (P = 0.0003) and edema index (P < 0.0001) had a significantly positive relation to VEGF expression. The positivity of Flt-1 and Flk-1 was mainly observed in tumor vessels; 44 cases (37.2%) were positive for the Flt-1 antibody and 37 cases (31.4%) for the Flk-1 antibody. The mean value of the edema index of the positive-Flt-1 group (5.220 ± 11.586) was significantly higher than that of the negative-Flt-1 group (1.782 ± 2.559) (P < 0.0001). The mean value of the edema index of the positive-Flk-1 group (3.925 ± 5.870) was slightly higher than that of the negative-Flk-1 group (2.671 ± 8.136) (P < 0.0001). Our data suggest that the expressions of VEGF and VEGF receptors positively relate to each other and to the formation of PTBE in patients with meningiomas.     

胶质瘤瘤周水肿、病理级别、Ki-67表达三者相关性研究

目的：探讨胶质瘤患者瘤周水肿（ PTBE）程度、肿瘤病理级别、Ki-67阳性表达率三者之间的相关性。方法收集新疆自治区人民医院神经外科2010—2013年经手术切除,病理证实的胶质瘤患者病历资料及标本74例,根据术前磁共振成像（ MRI ）资料判断肿瘤 PTBE程度,免疫组织化学检测Ki-67表达情况,HE染色区别肿瘤病理级别。结果本组研究中90.54%（67/74）伴发PTBE,其中Ⅰ、Ⅱ、Ⅲ、Ⅳ级别组PTBE发生率各为100%（3/3）、78.95%（15/19）、83.33%（15/18）及100%（34/34）;75.68%（56/74）Ki-67表达呈阳性;Ⅰ、Ⅱ、Ⅲ、Ⅳ级别组阳性率分别为0、36.84%（7/19）、94.44%（17/18）、94.12%（32/34）;无水肿、Ⅰ度水肿与Ⅱ水肿组中Ki-67表达阳性率分别为57.14%（4/7）、60.00%（6/10）、80.70%（46/57）。经Kruskal-Wallis H检验,PTBE在不同级别胶质瘤的总体差异有统计学意义（H＝11.304,P＝0.010）;Ki-67在不同级别胶质瘤中总体差异有统计学意义（H＝38.530,P﹤0.05）;Ki-67在不同PTBE组中表达的总体差异有统计学意义（ H＝6.478,P＝0.039）。Spearman等级相关分析显示胶质瘤PTBE程度随肿瘤病理级别增加而增加（ r＝0.385,P＝0.001）;Ki-67表达阳性率随肿瘤病理级别增加而增加（ r ＝0.692,P ﹤0.05）;Ki-67表达阳性率随胶质瘤 PTBE 增加而增加（ r ＝0.256,P＝0.028）。结论术前根据PTBE的大小可预测肿瘤的恶性程度与增殖活性,Ki-67既可作为肿瘤增殖活性的指标,也可当做病理分级的重要依据。     

A phase I trial of human corticotropin-releasing factor (hCRF) in patients with peritumoral brain edema

Background: Human corticotropin-releasing factor (hCRF) is an endogenous peptide responsible for the secretion and synthesis of corticosteroids. In animal models of peritumoral brain edema, hCRF has significant anti-edematous action. This effect, which appears to be independent of the release of adrenal steroids, appears mediated by a direct effect on endothelial cells. We conducted a feasibility and phase I study with hCRF given by continuous infusion to patients with brain metastasis.Patients and methods: Peritumoral brain edema documented by MRI and the use of either no steroids or stable steroid doses for more than a week were required. MRIs were repeated at completion of infusion and estimations by dual echo-image sequence (Proton density and T2-weighted images) of the amount of peritumoral edema were performed. The study was performed in two stages. In the feasibility part, patients were randomized to receive either 0.66 or 1 µg/kg/h of hCRF or placebo over 24 hours. The second part was a dose finding study of hCRF over 72 hours at escalating doses.Results: Seventeen patients were enrolled; only one was receiving steroids (stable doses) at study entrance; dose-limiting toxicity (hypotension) was observed at 4 µg/kg/h × 72 hours in two out of four patients, while zero of five patients treated at 2 µg/kg/h developed dose-limiting toxicities. Flushing and hot flashes were also observed. Improvement of neurological symptoms and/or exam were seen in 10 patients. Only small changes were detected by MRI. Improvement in symptoms did not correlate with changes in cortisol levels, and changes in cortisol levels were not correlated with changes in peritumoral edema.Conclusions: hCRF is well tolerated in doses up to 2 µg/kg/h by continuous infusion × 72 hours. Hypotension limits administration of higher doses. The observation of clinical benefit in the absence of corticosteroids suggests hCRF may be an alternative to steroids for the treatment of patients with peritumoral brain edema. Further exploration of this agent in efficacy studies is warranted.     

血管内皮生长因子与脑膜瘤瘤周水肿的关系

背景与目的：近年来对颅内原发和转移性肿瘤的分子生物学研究表明脑肿瘤的预后除与其临床分期、病理分级以及瘤周水肿等因素有关外，还与血管内皮生长因子（vascular endothelial growth factor，VEGF）有关。国内近年来有一些相关的报道，但系统研究不多。本研究探讨血管内皮生长因子的表达与脑膜瘤瘤周水肿的关系。方法：利用免疫组织化学方法检测脑膜瘤中VEGF的表达，用头颅MRI估计瘤周水肿的存在及程度。结果：30例脑膜瘤中，26例脑膜瘤有VEGF阳性表达，阳性率为76．7％。VEGF表达强阳性组与阴性组相比，水肿指数（edema index，E1）的差异有显著意义（EI=4．8与EI=I．2，P〈0．01）。结论：VEGF可能是形成脑膜瘤瘤周水肿的重要因素之一。     

Effects of glucocorticoid and chemotherapy on the peritumoral edema and astrocytic reaction in experimental brain tumor

To study the effects of glucocorticoids and chemotherapeutic agents on the pathophysiology of the tumor-induced brain edema, the site of Evans blue-albumin extravasation, the distribution of extravasated serum albumin, and the extent of local astrocytic reaction were examined in a rat model of implanted brain tumor. Experimental brain tumors were produced by implanting small pellets of Walker 256 carcinosarcoma into the cerebral cortex of Wistar rats. In the steroid group, rats were administered with intraperitoneal methylprednisolone succinate (15 mg/kg) daily on and after the 6th day postimplantation, and sacrificed on the 14th day. In the chemotherapy group, rats were given an intravenous injection of cyclophosphamide (30 mg/kg) on the 14th day, and sacrificed on the 21st day. Rats in the untreated group were sacrificed on the 14th day without any therapy. Each animal was sacrificed by the transcardiac perfusion with paraformaldehyde 30 min after intravenous injection of Evans blue. Firstly, coronal blocks of the brain were examined for Evans blue staining macroscopically. Paraffin embedded sections were studied for the Evans blue fluorescence and for the immunohistochemical reaction to serum albumin and GFAP. The examination of Evans blue demonstrated that the origin of extravasation of serum albumin was the tumor and the adjacent brain with dense tumor cell infiltration in any group of rats. The extravasated serum albumin distributed widely and the astrocytic reaction was prominent in the brain of the untreated group. A positive correlation was observed between the intensity of albumin immunoreaction and the degree of astrocytic proliferation. Chemotherapy effectively decreased the size of tumor and reduced the extravasation of serum albumin. The astrocytic reaction was however, not reduced. In the steroid group, the size of tumor was not significantly affected but the albumin extravasation as well as astrocytic reaction was markedly reduced. It was concluded that glucocorticoid is an effective drug against tumor-induced brain edema, which not only reduces the extravasation of serum components but also prevents histologic alterations of the brain.     

Cerebral edema associated with meningiomas: the role of peritumoral brain tissue

We undertook a morphological study of small pieces of peritumoral brain tissue removed from seven patients with meningiomas submitted to surgery. All patients had cerebral edema, as shown by preoperative C.T. and N.M.R.. Control specimens were obtained from five patients undergoing ventriculo-peritoneal shunt. The tissue fragments were fixed in glutaraldehyde-osmium and embedded in Epon. In semi-thin sections observed under light microscopy peritumoral endothelial cells exhibited voluminous cytoplasm and nucleus. Morphometrical evaluation confirmed that these endothelial cell nuclei were significantly larger than controls. Under the electron microscope those cells showed nuclei rich in euchromatin and cytoplasm rich in pinocytotic vesicles. The morphological changes observed suggest a process of dedifferentiation of brain peritumoral capillary cells and are compatible with an increase in permeability. Both events, which may be due to diffusion of a tumoral vascular permeability factor, favour the hypothesis that peritumoral brain tissue contributes to edema fluid that accumulates around meningiomas.     

卡托普利对小鼠在肺部照射后TGF-β1、TNF-α水平的影响

目的：探讨卡托普利在小鼠放射性肺损伤中对血清转化生长因子-β1（TGF-β1）、肿瘤坏死因子-α（TNF-α）的干预影响。方法：雄性C57／BL小鼠，设对照组、右肺单次照射10Gy组、右肺单次照射10Gy＋卡托普利组，于照射后36h、7d、15d、30d采集血液标本，ELISA法测血清中TGF-β1及TNF-α；同期取右肺组织以HE染色制成病理学标本。结果：10Gy照射组在照射后不同时段血清中TGF-β1水平及TNF-α水平均较对照组升高；而单次照射10Gy＋卡托普利组则表现为在不同时段均较对照组水平降低。析因分析结果为时间因素间、处理因素间、交互作用间均有统计学差异（P〈0．05）。病理结果显示10Gy照射组出现进行性加重的炎症改变，而单次照射10Gy＋卡托普利组则与对照组比较无明显区别。结论：卡托普利可以减低小鼠肺照射时TGF-β1、TNF-α等细胞因子浓度，并抑制放射性肺损伤的发生。     

p53 protein and epidermal growth factor receptor expression in human astrocytomas

Summary p53 mutations are the most frequently detected genetic alterations of gliomas, appearing in a similiar proportion of low and high grade astrocytomas, while the amplification ofepidermal growth factor receptor (EGFR) gene appears mainly in glioblastomas. Thus, these changes seem to delineate two subgroups of high grade astrocytomas: those originating from preexistent low grade astrocytomas and those originatingde novo. Paraffin-embedded surgical specimens from 56 human astrocytomas (8 pilocytic (I) astrocytomas, 9 low grade (II) fibrillary astrocytomas, 9 high grade (III) anaplastic astrocytomas and 30 glioblastomas) were analyzed immunohistochemically for the presence of p53 protein and EGFR. Approximately 41% of all cases were p53-protein-positive while 23% were EGFR-positive. Five cases (8.9%) were double-positive for p53 protein and EGFR. The p53-immunopositive nuclei were revealed in 16 cases (53.3%) of glioblastomas, 3 cases (33.3%) of high grade and 4 cases (44.4%) of low grade astrocytomas. None of pilocytic tumors was p53-positive. EGFR immunopositivity increased with the grade of malignancy (11,1%, 22.2% and 33.3%). Double EGFR-p53-positive cases occuried in similar proportions in all grades (approximately 10%) and did not show different survival rate. There were no differences between average age of patients with only-p53-positive, p53-negative (pilocytic tumors excluded) and only-EGFR-positive tumors.