Microvascular structural entropy: A novel approach to assess angiogenesis in pituitary tumors

Entropy, a measure of the degree of disorder in a system, has recently been used in different morphologic studies to quantify regularity. Our aims were (a) to study the structural organization of the microvascular bed in prolactin (PRL)-producing adenomas and carcinomas, the most vascularized of pituitary tumors, by assessing microvascular structural entropy (MSE), and (b) to determine whether the degree of disorder of the capillary bed correlates with tumor cell proliferation as estimated by MIB-1 labeling, microvessel density (MVD), the most widely used method of quantifying blood vessel formation, and various clinicopathologic parameters (gender, age, tumor size and invasiveness). The morphometric study demonstrated statistically significant differences in MIB-1 labeling, MVD, and MSE between PRL-producing adenomas and carcinomas. Unlike MIB-1 labeling index (PRL-producing adenomas 1.5±0.27; carcinomas 15.0±4.04) and MVD (PRL-producing adenomas 2.7±0.34; carcinomas 4.2±0.72), the MSE values were significantly higher in adenomas (171.5±25.37) than in carcinomas (67.9±17.45). These results indicate that PRL-producing carcinomas have a less chaotic distribution of vessels than benign adenomas. In contrast to a lack of correlation between, microvessel density and other morphometric parameters, a strong negative correlation was found between MSE and MIB-1 labeling index (r=0.511, p=0.003). It thus appears that regular, less chaotic microvascular geometry contributes to increased proliferative activity in PRL cell tumors. Analysis of MSE may provide an independent parameter of tumor behavior, and contributes to a better understanding of the role of microvasculature in pituitary tumor progression.     

The significance of angiogenesis in malignant pheochromocytomas

The purpose of this study was to investigate tumor angiogenesis in a series of benign and malignant pheochromocytomas and to determine whether there is a correlation between angiogenesis and the presence of distant metastases. In this study, the CD31 monoclonal antibody was selected to measure intratumoral microvessel density. Nineteen patients with malignant pheochromocytomas and nineteen patients with benign pheochromocytomas who underwent operation were studied. In order to quantify intratumoral microvessel density, the total number of pixels of CD31-positive reactivity was assessed and expressed as a percentage of the total tissue area in the analyzed field. Analysis of variance revealed a statistically significant correlation between malignancy and intratumoral microvessel density (p=0.0009). Although there was a considerable variability in the intratumoral microvessel density from tumor to tumor within both the benign and the malignant group, a percentage of more than 28.5% anti-CD31 stained area was found only in malignant tumors. In conclusion, this study shows that the mean intratumoral microvessel density in malignant pheochromocytomas is increased approximately two-fold as compared with benign tumors. However, the clinical significance of this prognostic marker is rather weak, because only 4 of the 19 malignant pheochromocytomas had microvesel density higher than this threshold of 28.5%.     

碱性成纤维细胞生长因子与卵巢癌的关系

目的　探讨碱性成纤维细胞生长因子 (basic fibroblast growth factor,b FGF)对卵巢癌细胞增殖、浸润和肿瘤血管生成的影响 ,及 b FGF单克隆抗体 (b FGF monoclonal antibody,b FGF- MAb)的治疗作用。　方法　将人卵巢癌细胞株 SKOV3接种于 2 4孔板 ,加入不同浓度的 b FGF,每日行结晶紫染色后测定光密度 (D4 90 )值 ,绘制细胞生长曲线 ;将 SKOV3细胞团接种于铺设有细胞外基质凝胶的 4孔板 ,每日测定癌细胞在凝胶中的浸润距离 ;建立 SKOV3细胞裸鼠皮下移植瘤模型 ,每周两次分别将 b FGF、b FGF-MAb和生理盐水注射于移植瘤周围 ,8周后测量肿瘤体积 ;对移植瘤组织切片行 因子的免疫组化染色、测定肿瘤内微血管密度 (microvessel density,MVD)。　结果　 b FGF能促进 SKOV3细胞增殖并呈浓度依赖 ,实验第 5天 ,5 ng/ml、10 ng/ml组细胞 D4 90 值是对照组的 1.0 9倍和 1.2 1倍 ;b FGF能促进 SKOV3细胞浸润并呈浓度依赖 (P<0 .0 5 ) ,第 7天 ,5 ng/ml、10 ng/ml组细胞浸润距离分别是对照组的 1.5 3倍和2 .4 5倍 ;b FGF组移植瘤体积和 MVD分别是对照组的 1.80倍和 1.4 6倍 (P<0 .0 5 ) ,b FGF- MAb组移植瘤体积和 MVD分别是对照组的 6 3.7%和 6 2 .8% (P<0 .0 5 )。　结论　b FGF能明显促进卵巢癌细胞的增殖、     

星形细胞瘤微血管密度与病理分级的相关性

目的 探讨星形细胞瘤微血管密度（MVD）与病理分级的关系。方法 对磁共振成像（MRI）术前诊断及手术病理证实的幕上星形细胞瘤石蜡标本进行免疫组化染色,测定MVD。结果 随着星形细胞瘤级别的增加,MVD值增高,且Ⅰ、Ⅱ级与Ⅲ、Ⅳ级之间有显著差异（P＜0．01）;MVD随着肿瘤直径增大而增加,但无显著差异（P＞0．05）。结论 MVD与星形细胞瘤恶性表型及生物学行为密切相关,可作为判断星形细胞瘤恶性程度的指标。     

黄芪多糖对糖尿病大鼠微血管病变的作用及机制的研究

目的：探讨黄芪多糖（APS）对糖尿病大鼠微血管病变的影响以及对糖尿病的治疗作用及机制。方法：成年,健康SD大鼠40只,雌雄不限,分成四组：正常对照组,糖尿病组（腹腔注射四氧嘧啶200mg/kg),APS组（造模成功后用APS治疗）,优降糖组（造模成功后用优降糖治疗）。治疗两周时测一次血糖,四周后,测血糖;颈动脉取血测定血清胰素水平,NO和MDA含量。应用形态定量的方法比较各组的心肌病理变化。结果：腹腔注射alloxan(200mg/kg)后的SD大鼠血糖浓度显升高,血清NO,MDA,胰岛素水平明显改变。APS治疗四周后,血糖浓度明显下降,与优降糖治疗组无明显差异,血清NO较未治疗组明显升高（P＜0．01）,血清MDA较未治疗组明显减少（P＜0．01）,血清胰岛素水平升高（P＜0．05）,光镜下观察,糖尿病大鼠的心肌毛细血管数量减少,基底膜增厚,微血管与心肌纤维的比率显减低,这些改变都可被APS改善.结论：APS有降低血糖和保护血管内皮细胞的作用,这可能与APS减轻氧自由基的损伤,影响NO的产生以及促进胰岛B细胞的损伤的恢复有关。     

鼻咽癌组织中微血管的分布

目的：观察鼻咽癌组织中微血管的分布及存在状况,探讨其与鼻咽癌的临床病理联系。方法：采用免疫组织化学Ｓ－Ｐ法,检测血栓调节蛋白在鼻咽癌血管内皮细胞的表达,进行微血管的定性半定量研究。结果：鼻咽癌组织中微血管的分布不均匀。极性消失。血管呈分支芽状弥漫分布于癌组织中,或呈条索状围绕癌细胞团。微血管的数目与癌细胞的增殖指数屯预后正相关。结论：鼻咽癌组织中微血管数与患者的生存期有关。     

膀胱移形细胞癌微血管密度与病理组织学分级和预后的关系

目的：探讨肿瘤血管形成及其密度与膀胱移行细胞癌生物学行为的关系。方法：应用免疫组织化学方法检测了６７例膀胱移行细胞癌组织中ＦⅧ因子相关抗原的表达和肿瘤组织中微血管的长度密度（ＬＶ）和微血管截面数（ＱＡ）。结果：膀胱癌组织中微血管ＬＶ明显高于正常膀胱（Ｐ〈０．０１）。但高分化膀胱癌微血管ＬＶ与正常膀胱无显著性差异（Ｐ〉０．０５）。膀胱癌分化越差,微血管ＬＶ越高;有肌层浸润组微血管ＬＶ明显高于无肌层浸     

Receptor tyrosine kinase tie 1 mRNA is upregulated on cerebral microvessels after embolic middle cerebral artery occlusion in rat

Tie 1 is an endothelial specific transmembrane receptor tyrosine kinase and may be required during angiogenesis. Using in situ hybridization, we measured tie 1 mRNA in ischemic brain (n=15). Rats were subjected to middle cerebral artery (MCA) occlusion by a single fibrin rich clot. Expression of tie 1 was not detected in non ischemic brain. Cerebral microvessels expressed tie 1 in the ischemic lesion as early as 2 h after MCA occlusion. The number of microvessels containing tie 1 mRNA decreased in the ischemic lesion at 8 h after MCA occlusion. However, expression of tie 1 increased on microvessels at 24 h and 14 days after ischemia and tie 1 was primarily localized to the microvessels bordering pan necrotic tissue. Ninety-seven percent of cerebral vessels which expressed tie 1 mRNA had diameters of 3.7+/-0.17 microm. Our findings suggest a role for tie 1 in cerebral microvascular remodeling after embolic stroke.     

喉鳞癌瘤内微血管及微淋巴管形态计量研究及临床意义

目的:研究喉鳞癌瘤内微血管和微淋巴管形态、分布、密度,以及相关临床意义。方法:采用5’-Nase-AlPase双重酶组织化学法和HE染色对40侧喉鳞癌标本冰冻切片进行研究。结果:光镜下微血管呈蓝色,微淋巴管呈棕色。除转移组微血管密度显著高于未转移组外,与其余临床指标均未见相关性。结论:瘤内微血管密度与淋巴转移有明显相关,而微淋巴管密度未发现明显临床意义,其机制待深入研究。     

VEGF,PDGF和MVD在喉癌中的表达及临床意义

目的 探讨血管内皮生长因子(vascular endothelial growth factor,VEGF),血小板来源的内皮生长因子(platelet-derived endothelial growth factor,PDGF),Ⅷ因子测定的微血管密度(microvessel density,MVD)与喉癌微血管生成、临床分期和病理分级的关系。方法 应用免疫组织化学LASB法检测1998～1999年40例喉鳞状细胞癌和11例喉正常粘膜VEGF、PDGF、微血管密度的表达情况,结合临床相关因素进行统计分析。结果 喉鳞状细胞癌中VEGF表达在肿瘤T分级、临床分期、淋巴结转移和病理分级中有统计学意义(P<0.05)。PDGF计数标识指数与病人肿瘤T分级、临床分期中差异有统计学意义(P<0.05)。MVD测定均数在早、晚期分组中有统计学意义(P<0.05)。结论 喉癌的发展、侵袭需要持续的新生血管,本实验提示肿瘤增殖与理论相符,VEGF、PDGF和MVD可作为临床预测重要参考指标。