Glut-1和VEGF在血管瘤和血管畸形中的表达及意义

目的：检测萄萄糖转运蛋白-1（Glut-1）和血管内皮细胞生长因子（VEGF）在血管瘤和血管畸形中的表达，探讨他们在血管瘤发生发展过程中的作用。方法：采用免疫组化SABC法检测30例增殖期血管瘤，30例消退期血管瘤，22例血管畸形（10例蔓状血管瘤和12例海绵状血管瘤）及5例正常皮肤组织中Glut-1和VEGF的表达。结果：增殖期血管瘤中Glut-1、VEGF的表达均显著高于消退期血管瘤、血管畸形和正常皮肤（P〈0．01），消退期血管瘤中Glut-1的表达也明显高于血管畸形和正常皮肤（P〈0．01），而消退期血管瘤中VEGF的表达与血管畸形，正常皮肤的差异不具有显著性（P〉0．05）。结论：Glut-1和VEGF在血管瘤的发生发展中可能起到很重要的作用，通过检测Glut-1在血管瘤和血管畸形中的表达情况能够比较准确的区分血管瘤和血管畸形，Glut-1或许可以作为区分血管瘤和血管畸形的一种较特异的参考指标。     

血管瘤和血管畸形:经验、进展与挑战

过去的十年间，人们对血管瘤和血管畸形的认识有了广泛的提高，即使在中文文献中，更多作者已不再使用1863年由细胞病理学之父Virchow提出的的分类概念（毛细血管瘤、海绵状血管瘤和蔓状血管瘤），而是划分了血管瘤和血管畸形，并更多使用血管瘤、海绵状静脉畸形及动静脉畸形等更合理的概念，这是最重要的进展。同时不少作者都在撰文中注明了血管瘤分期（增生、稳定和消退期）。     

缺氧诱导因子1α过表达对前列腺癌细胞血管生成能力的影响

目的：观察转染缺氧诱导因子1α（HIF-1α）对人前列腺癌细胞血管形成相关蛋白的影响,并探讨其分子机制。方法：用脂质体Lipofectamine2000包装重组真核表达载体pCDNA3.1（-）/HIF-1α后转染人前列腺癌细胞LNCaP,600μg/ml G418筛选稳定表达的抗性克隆。免疫荧光及Western印迹法鉴定HIF-1α过表达,Western印迹法检测血管形成相关蛋白血管内皮生长因子（VEGF）、iNOS、促血管生成素2（Ang-2）。结果：与未转染细胞LN-CaP相比,转染细胞LNCaP/HIF-1α中出现明显的HIF-1α蛋白条带,并激发出较强荧光,VEGF、iNOS表达增加,Ang-2未见明显变化。结论：HIF-1α过表达能够诱导LNCaP细胞血管形成相关蛋白表达增多,进而增强其体外血管形成能力。     

促血管生成素-1、2及Tie2在血管瘤及血管畸形中的表达及意义

目的探讨促血管生成素-1（Ang-1）、促血管生成素-2（Ang-2）及其受体Tie2在血管瘤和血管畸形组织中的表达及意义。方法应用免疫组织化学S—P方法，测定血管瘤、血管畸形的血管内皮细胞中Ang-1、Ang-2及Tie2的表达。结果Ang-2、Tie2的表达在增生期血管瘤最强；在退化期血管瘤中的表达次之；而在血管畸形中表达较弱，与小儿正常皮肤表达无显著性差异。而Ang-1的表达，各组差异无统计学意义。结论Ang-1、Ang-2及其受体Tie2在血管瘤的血管生成以及血管瘤的自然消退过程中可能起着重要的作用；Ang-1、Ang-2及其受体Tie2的表达可能与血管畸形的发病无明显关系。     

促血管生成素家族在大肠腺癌中的表达及与微血管密度和临床病理特征的关系

目的 探讨促血管生成素-1（Ang-1）、促血管生成素-2（Ang-2）、促血管生成素受体（Tie-2）及血管内皮生长因子（VEGF）在大肠腺癌及癌旁正常组织中的表达，及与微血管密度（MVD）和临床病理特征的关系。方法 采用免疫组织化学方法检测Ang-1、Ang-2、Tie-2及VEGF在45例大肠腺癌及10例癌旁正常组织中的表达。结果 大肠腺癌组织中的Ang-2蛋白及VEGF蛋白明显高于癌旁正常组织（P〈0．01），腺癌的分化程度越低，Ang-2及VEGF蛋白的表达率越高（P〈0．05），Ang-2与VEGF蛋白的表达存在明显正相关性（r=0．997，P〈0．01）；大肠腺癌组织中的Ang-1蛋白明显低于癌旁正常组织（P〈0．01），腺癌的分化程度越高，Ang-1蛋白的表达率越高（P〈0．05）；Tie-2蛋白在大肠腺癌和癌旁正常组织中的表达差异无统计学意义（P〉0．05）。大肠腺癌的分化程度越低，MVD越高（P〈0．05），腺癌组织中Ang-1蛋白阳性表达组MVD明显低于阴性表达组（P〈0．01），Ang-2蛋白阳性表达组MVD明显高于阴性表达组（P〈0．01）。≥5cm及有淋巴结转移的大肠腺癌组织中，Ang-2蛋白的表达明显增加（x^2=8．889，P〈0．01；x^2=10．020，P〈0．01）。结论 在大肠腺癌组织中，相对Ang-1占优势的Ang-2的过度表达，可能在肿瘤的血管生成和进展过程中起着重要作用。     

网状铜丝留置联合平阳霉素注射治疗复杂性海绵状静脉畸形

目的 评价网状铜丝留置结合平阳霉素注射治疗体表软组织内复杂性海绵状静脉畸形的效果.方法 通过体检和磁共振检查明确静脉畸形的位置,用直径0.2 mm铜丝在畸形血管团内反复穿刺,呈网状留置于畸形病灶内.穿刺结束后向残余畸形血管内注射平阳霉素8 mg.8～10d后拔出铜丝,挤出坏死物质,换药至穿刺孔愈合.术后定期行MRI检查,评估疗效.结果 2002年1月至2008年12月,共治疗海绵状静脉畸形45例.经1～3年随访,51.1%(23/45)病灶显著缩小甚至接近消失;42.2%(19/45)病灶有所缩小;6.67%(3/45)病灶无明显变化.本组45例均未发生侵袭性感染等并发症.结论 网状铜丝留置结合平阳霉素注射是治疗大面积复杂性海绵状静脉畸形的有效方法.     

婴幼儿海绵状血管瘤的再分类及临床与实验室依据

目的 婴幼儿海绵状血管瘤的诊断存在性质上的混淆,故需对该组疾病进行合理的再分类。方法 通过对6个月龄以内进行正规激素治疗的16例婴幼儿海绵状血管瘤患者进行了为期逾8年的临床随访,分别检测细胞增殖标志物增殖细胞核抗原(proliferating cell riuclear antigen,PCNA)、血管形成标志物碱性成纤维细胞生长因子(basic fibroblastic growth factor,bFGF)、血管内皮细胞生长因子(vascular endothelial growth factor,VEGF)及组织学特征等。结果 可以根据最后是否消退分为两组,两组间无论在预后、上述标志物表达、体征、生长特征等方面都存在明显差异。结论 取消婴幼儿海绵状血管瘤这一诊断,重新划分为皮下毛细血管瘤与海绵状静脉畸形两类,将有利于正确的诊疗方案选择。     

VEGF、TGF-α和TGF-β1在血管瘤和血管畸形中的表达

目的了解血管形成因子VEGF、TGF-α、TGF-β1在血管瘤中的表达,进一步认识血管形成因子在血管瘤发病机制中的作用.方法采用SABC法对血管瘤、血管畸形和正常皮肤进行免疫组化染色,观察VEGF、TGF-α、TGF-β1在血管瘤及血管畸形中的表达.结果在正常皮肤血管中VEGF、TGF-α、TGF-β1不表达,VEGF、TGF-α在血管瘤中表达,而在血管畸形组织中不表达或低表达(P＜0.05).TGF-β1在血管瘤中低表达,而在血管畸形组织中不表达.结论血管形成因子在血管瘤的发展过程中起到重要的作用,VEGF及TGF-α可作为区分血管瘤和血管畸形的标志物.     

促血管生成素-1、2及Tie2在血管瘤及血管畸形中的表达及意义

目的 探讨促血管生成素-1(Ang-1)、促血管生成素-2(Ang-2)及其受体Tie2在血管瘤和血管畸形组织中的表达及意义.方法 应用免疫组织化学S-P方法,测定血管瘤、血管畸形的血管内皮细胞中Ang-1、Ang-2及Tie2的表达. 结果 Ang-2、Tie2的表达在增生期血管瘤最强;在退化期血管瘤中的表达次之;而在血管畸形中表达较弱,与小儿正常皮肤表达无显著性差异.而Ang-1的表达,各组差异无统计学意义. 结论 Ang-1、Ang-2及其受体Tie2在血管瘤的血管生成以及血管瘤的自然消退过程中可能起着重要的作用;Ang-1、Ang-2及其受体Tie2的表达可能与血管畸形的发病无明显关系.     

缺氧诱导因子1α过表达对前列腺癌细胞血管生成能力的影响

目的:观察转染缺氧诱导因子1α(HIF-1α)对人前列腺癌细胞血管形成相关蛋白的影响,并探讨其分子机制。方法:用脂质体Lipofectamine2000包装重组真核表达载体pCDNA3.1(-)/HIF-1α后转染人前列腺癌细胞LNCaP,600μg/ml G418筛选稳定表达的抗性克隆。免疫荧光及Western印迹法鉴定HIF-1α过表达,Western印迹法检测血管形成相关蛋白血管内皮生长因子(VEGF)、iNOS、促血管生成素2(Ang-2)。结果:与未转染细胞LN-CaP相比,转染细胞LNCaP/HIF-1α中出现明显的HIF-1α蛋白条带,并激发出较强荧光,VEGF、iNOS表达增加,Ang-2未见明显变化。结论:HIF-1α过表达能够诱导LNCaP细胞血管形成相关蛋白表达增多,进而增强其体外血管形成能力。     

Trans-mesencephalic arteries and veins

Summary The authors present the trans-mesencephalic arteries and their rôle in the differenciation of pure and secondary vein of Galen arterio-venous malformations (AVM). They illustrate the trans-mesencephalic draining veins of the so-called venous angiomas, which are normal variants, often associated with cavernous haemangiomas representing the clinically active lesion.     

葡萄糖转运蛋白-1在血管瘤和血管畸形中的表达及其意义

目的检测葡萄糖转运蛋白-1(glucose transporter-1,Glut1)在血管瘤和血管畸形组织中的表达并探讨其意义。方法各阶段婴幼儿血管瘤标本52例、海绵状静脉畸形25例、动静脉畸形9例、毛细血管畸形2例、正常皮肤软组织5例。应用En Vision法免疫组化染色检测Glut1在上述标本中的表达。结果增生早期,较多血管瘤内皮细胞表达Glut1;增生中期,绝大部分微血管内皮细胞和散在分布的内皮细胞表达Glut1;增生晚期,Glut1表达迅速减弱;消退期血管瘤微血管内皮细胞不表达Glut1。所有海绵状静脉畸形、动静脉畸形、毛细血管畸形、正常皮肤软组织中的小动静脉和微血管均不表达Glut1。结论Glut1是血管瘤内皮细胞发展过程中的一种表型,而不是其固有特征,Glut1表达是血管瘤内皮细胞适应代谢需要而产生的。     

Development of an intracranial ependymoma at the site of a pre-existing cavernous malformation

BACKGROUND: The ability of vascular anomalies to induce neoplastic transformation in normal brain parenchyma has been suggested but not demonstrated. We present a novel case in which a patient with a pre-existing cavernous malformation developed an adjacent ependymoma. CASE DESCRIPTION: A 72-year-old man developed an anaplastic ependymoma at the site of a pre-existing cavernous malformation. This is the first documented instance of an ependymoma developing at the site of an existing cavernous malformation. The colocalization of both lesions and the low incidence of supratentorial ependymomas in this age group makes it unlikely that their coexistence represents a random event. Immunohistochemistry demonstrated vascular endothelial growth factor (VEGF) production by the cavernous malformation and robust VEGF receptor expression by the ependymoma. CONCLUSIONS: Based on these findings, we suggest that production of VEGF by vascular malformations may play a role in the neoplastic transformation of adjacent tissue.     

Diagnostic imaging of angiographically occult vascular malformations.

Occult vascular malformations of the central nervous system include cavernous malformations, capillary telangiectasis, and developmental venous anomalies (DVAs). Cavernous malformations are prone to multiple small hemorrhages and may enlarge with time. They have a heterogeneous appearance on CT and MR imaging with areas of hemorrhage in various states of evolution and sometimes calcifications. Developmental venous anomalies and capillary telangiectasis are usually incidental findings on imaging studies. They usually are not the cause of pathology by themselves, although DVAs can be associated with cavernous malformations in 8% to 33% of cases.     

Expression of the Vascular Endothelial Growth Factor and Angiopoietins in Mucoepidermoid Carcinoma of Salivary Gland

Disrupted coordination of angiogenesis regulating signals, among them the vascular endothelial growth factor (VEGF) and angiopoietins (Angs), has been associated with abnormal angiogenesis and tumor progression. While VEGF induces endothelial cell proliferation, thereby initiating vessel formation, Angs are subsequently required for mural cell attachment, thus influencing remodeling and maturation of this vasculature. In addition to tumor cell, endothelial and mural cells, as well as myofibroblasts may also contribute to the secretion of these factors. In this study, we have analyzed by immunohistochemistry the expression of VEGF, Ang-1, Ang-2 and the Angs receptor Tie2 in both the stroma and tumor cells of mucoepidermoid carcinoma (MEC) of salivary gland. We have demonstrated that when myofibroblasts were detected adjacent to the cancer cells, they were frequently associated with intense positive staining for Ang-1 and Ang-2, and no reactivity to VEGF and Tie2. These myofibroblast-rich Ang-1 and Ang-2-stained areas were more commonly found in high-grade MEC cases than in low-grade ones. As for the malignant cells, they frequently expressed all proteins studied, but Ang-2 and VEGF were detected at higher levels compared to Ang-1 and Tie2. Our results indicate that the MEC environment favors cooperative activity between Angs and VEGF in modulating vascular growth and tumor aggressiveness.     

自体静脉移植再狭窄与MMP-1、MMP-2及TIMP-2的表达

目的：通过测定自体静脉移植术后移植静脉管腔狭窄度、金属基质蛋白酶-1（MMP-1），MMP-2金属蛋白酶特异性抑制剂-2（TIMP-2）的表达，探讨自体静脉移植术后再狭窄与金属蛋白酶家族，（MMps）及其特异性抑制剂（TIMP）s的关系。方法：60只Wister大鼠均行颈静脉腹主动脉移植术，在术后28d后取出移植静脉行病理学检查测量移植静脉管腔狭窄度，根据移植静脉管腔狭窄程度，分成正常、轻、中、重4组，并采用免疫组织化学方法（ABC法）行MMP-1，MMP-2及TIMP-2的检测。结果：静脉移植后，移植静脉出现不同程度的狭窄。在狭窄的移植静脉， MMP-1、MMP-2和TIMP-2高水平表达；静脉狭窄程度越重，MMP-1、MMP-2和TIMP-2表达强度越高，MMP-1、MMP-2的升高幅度高于TIMP-2的升高幅度。结论：自体静脉移植术后移植血管再狭窄的发生和发展与MMPs及TIMPs的表达失衡密切相关。     

The association of venous and cavernous malformations

Summary Four cases of venous malformation associated with a cavernous malformation are reported. Because cavernous malformations are often angiographically occult and do not have a characteristic appearance on computed tomography (CT), they are seldom recognized preoperatively and may be missed if the surgical specimen is not carefully reviewed.This association, however, may not be rare and may explain the presence of symptomatic venous malformations. Magnetic resonance (MR) imaging is particularly sensitive in detecting cavernous malformations and is highly specific. It is recommended that every symptomatic venous malformation be worked-up with a high field strength MR Unit.     

The juxtaposition of a capillary telangiectasia, cavernous malformation, and developmental venous anomaly in the brainstem of a single patient: case report

OBJECTIVE AND IMPORTANCE: Capillary telangiectasias, cavernous malformations, and developmental venous anomalies are all vascular malformations that occur on the capillary-venous side of the cerebral circulation. The associations of capillary telangiectasias with venous malformations, cavernous malformations with venous malformations, and capillary telangiectasias with cavernous malformations have all been described; however, the association of all three lesions in a single patient is extremely rare. CLINICAL PRESENTATION: A 52 year-old Caucasian woman presented to our clinic with an extended history of confusion, distorted visual perceptions, photophobia, neck pain, swallowing problems, and poor balance. The patient's examination was remarkable for difficulty concentrating, mild rotatory nystagmus, subtle decreased sensation over the left side of the face and body, and brisk reflexes. Review of the patient's magnetic resonance imaging examination demonstrated a cavernous malformation, a capillary telangiectasia, and a developmental venous anomaly located adjacent to one another in the brainstem. INTERVENTION: Given the patient's complex constellation of symptoms and relatively mild neurological findings, it was difficult to ascribe any one of them to a specific vascular malformation. Conservative management of this patient's vascular malformations was decided upon. CONCLUSION: Juxtaposition of these three different vascular lesions in the brainstem of an otherwise normal individual suggests a relationship among them. Although there are several theories that link similar associations through physiological mechanisms such as venous hypertension, we propose that a developmental event disrupting local capillary-venous pattern formation is a plausible alternative.     

四种中药复方对糖尿病肾病大鼠肾脏组织中Ang-1、Ang-2、Tie-2和VEGF mRNA表达影响

目的：观察四种中药复方对糖尿病大鼠肾脏的肾脏血管生成素、Tie-2和VEGF表达的影响。方法：取链脲霉素诱导SD大鼠DN模型72只,分为模型对照组、益气养阴方组、滋补肝肾方组、补气养血方组、温肾健脾方组和阳性对照组,每组12只;另取12只大鼠为正常对照组。连续经口灌胃给药8周后,收集尿液测定U-TP、U-GLU和U-β2微球蛋白生化指标,用RT-PCR测定肾脏组织中Tie-2、VEGF mRNA的表达。结果：益气养阴方、滋补肝肾方、补气养血方、温肾健脾方均能显著降低Ang-1mRNA表达（P〈0.05,P〈0.01）;益气养阴方组大鼠肾脏Ang-2和Tie2 mRNA表达显著降低（P〈0.05,P〈0.01）;给予补气养血方和温肾健脾方后,大鼠的肾脏Ang-2 mRNA表达显著降低（P〈0.01）。结论：四种中药复方均能有效降低Ang-1、Ang-2和VEGF mRNA的表达;参芪地黄汤还可降低Tie-2 mRNA的表达,表明四种复方可通过抑制血管重建作用而治疗大鼠糖尿病肾病,其中参芪地黄汤效果较佳。