MMP-2和VEGF在肾细胞癌中的表达及其与MVD的相关性

目的探讨肾细胞癌（RCC）组织中基质金属蛋白酶-2（MMP-2）与血管内皮生长因子（VEGF）表达与血管生成的关系。方法用免疫组织化学SP法检测57例肾细胞癌、9例正常肾组织中的MMP-2与VEGF的表达,计数微血管密度（MVD）,血管生成采用CD34免疫组化染色方法标记微血管内皮。结果 RCC组织中MMP-2与VEGF表达明显高于正常肾组织（P〈0.05）,不同临床分期的RCC组织中MMP-2与VEGF表达差异有统计学意义（P〈0.05）,不同病理类型的RCC组织中MMP-2与VEGF表达差异无统计学意义。MVD与VEGF、MMP-2蛋白表达之间呈显著相关性（P〈0.05）;VEGF与MMP-2蛋白表达之间有显著相关性（P〈0.05）。结论 MMP-2与VEGF的表达可反映RCC侵袭和转移潜能的生物学指标,对临床判断肾癌预后有着直接意义。     

不同吸氧方式对新生鼠视网膜血管发育的影响

目的：吸氧是早产儿视网膜病的高危因素之一,目前吸入氧浓度、吸氧方式等与早产儿视网膜病的关系仍有争议。该实验通过研究不同吸氧方式对新生鼠视网膜血管发育的影响,为早产儿临床合理用氧提供实验依据。方法：选择7日龄C57BL/6 J新生小鼠144只,随机分为6组,每组24只。实验组1:吸入氧浓度(F iO2)由30%逐渐升高至75%后突然中断吸氧;实验组2:F iO2由75%逐渐降低直至停氧;实验组3:吸75%高氧5天后骤然停氧;实验组4:吸75%高氧5天后逐渐降低F iO2直至停氧;实验组5:第1天吸75%高氧,第2天吸空气氧,交替进行,连续6 d;对照组:置于同实验条件下的空气中。实验组1,2,3,5和对照组分别于P12(生后第12天),P14,P17视网膜铺片(ADP酶染色法),实验组4于P14,P17,P22视网膜铺片,各组均在P17行视网膜切片(苏木素-伊红染色法)观察视网膜血管的增生和发育情况。结果：①视网膜铺片显示:对照组:P12见少量无灌注区,周边血管结构清晰,P14无灌注区消失,血管形态基本正常,P17血管形态全部正常。实验组1,3,5:P12视网膜中央部有大片无灌注区,血管收缩、闭塞,P14新生血管开始形成,P17大量新生血管形成。实验组4:P14视网膜中央部大片无灌注区,有少量新生血管形成,P17无灌注区缩小,血管走行基本正常,深层血管有阻塞,P22血管发育基本正常。实验组2:铺片显示视网膜血管形态与对照组相似。②视网膜切片显示:实验组1,2,3,4,5小鼠突破视网膜内界膜的新生血管内皮细胞核的数目分别为49.50±1.36,5.17±0.67,47.68±4.70,5.74±2.37,29.15±2.48个,对照组为1.22±0.20个。实验组1,3,5与对照组相比差异均有显著性(P<0.05),实验组2,4与对照组相比差异无显著性(P>0.05)。结论：不同吸氧方式对视网膜血管发育产生不同的影响,吸入氧浓度波动较大、吸入高浓度氧后突然停氧可严重影响新生鼠视网膜血管的发育,产生类似早产儿视网膜病的病变。因此临床上应尽早稳定早产儿的生命体征,减少氧疗,严密监测用氧情况,采取逐渐降低氧浓度的吸氧方式,并尽量避免氧浓度波动过大。     

翼状胬肉组织中血管拟态的初步研究

目的探讨血管拟态在翼状胬肉发病过程中的发生机制及其作用。方法对218例手术切除的翼状胬肉标本在光镜下进行形态学观察,其中97例行免疫组织化学、免疫组织化学（一抗为CD34、层粘连蛋白、血管内皮生长因子）联合过碘酸-希夫（PAS）组织化学双标染色,即一抗37℃孵育60min,二抗37℃孵育30min,辣根过氧化酶显色剂显色,0．5％高碘酸氧化10min,Schiffs液避光染色20min,Mayer苏木素复染3min,流水浸洗,中性树胶封片。结果218例翼状胬肉组织中97例出现了血管拟态的变化,表现为管状型和网状基质型。PAS染色血管拟态区网眼间隔染成紫红色。CD34免疫组织化学联合PAS组织化学双标染色显示构成网眼区内的支架突起与细胞为CD34阳性,外包绕有PAS染成紫红色的细胞外基质样物。层粘连蛋白免疫组织化学联合PAS组织化学双标染色显示血管内皮细胞与血管壁表达层粘连蛋白,但管样区内的细胞无明显阳性反应。血管内皮生长因子免疫组织化学联合PAS组织化学双标染色显示网状区内的纤维母细胞样细胞呈阳性反应,网眼间隔与细胞外基质物PAS染成紫红色。结论血管拟态结构存在于翼状胬肉组织中,血管拟态是其血供途径之一。     

胰腺导管腺癌Sp1、PTEN和KLF4的表达及其与微血管密度的关系

目的:观察胰腺导管腺癌组织Sp1、PTEN和KLF4的表达,探讨其在肿瘤血管形成中的可能作用。方法:采用免疫组织化学ABC方法,半定量检测30例胰腺导管腺癌组织Sp1、PTEN和KLF4的表达,并选用CD31抗体染色计数肿瘤组织内微血管密度(MVD)。结果:Sp1的阳性表达定位于细胞核;KLF4和PTEN的阳性表达分布于细胞质。20例(67%)有Sp1高表达;20例(67%)有KLF4胞质阳性表达;仅7例(23%)PTEN呈胞质阳性表达。肿瘤细胞的Sp1表达强度与肿瘤组织内MVD值呈正相关(r=0.765,P<0.05)。Sp1高表达的肿瘤细胞其胞质PTEN和KLF4呈低表达(P<0.001,P<0.05)。结论:Sp1和PTEN与原发性胰腺导管腺癌的肿瘤血管形成密切相关,PTEN和KLF4在胰腺癌中可能起抑癌基因作用。     

Expression of EphA2 and VEGF in squamous cell carcinoma of the tongue: correlation with the angiogenesis and clinical outcome

Eph-ephrin binding has been linked to tumor biology and VEGF has been reported to participate in the tumor angiogenesis regulated by Eph-ephrin. The present study was designed to evaluate the expression of EphA2 and VEGF in relation to angiogenesis and clinical outcome in squamous cell carcinoma of oral tongue. Immunohistochemical staining was used to determine the protein expression levels of EphA2 and VEGF in 59 surgically resected tongue carcinomas and 10 tumor-free mucosas. In all cases, microvessel density (MVD) was evaluated by counting CD34-reactive endothelial cells or endothelial cell clusters. Both EphA2 and VEGF staining activities in squamous cell carcinoma of oral tongue were more significant than those in normal mucosa (P < 0.01). MVD had significant correlations with EphA2 and VEGF expression (P < 0.01). The EphA2, VEGF, and MVD were significantly correlated with tumor size, clinical stage, lymph invasion, recurrence, and distant metastasis (P < 0.05). Multivariate analysis showed EphA2, VEGF expression, MVD, and clinical stage had an independent prognostic effect on overall survival. We conclude that the overexpression of EphA2 and VEGF are related to malignancy in squamous cell carcinoma of oral tongue. Clinical outcomes raised the possibility that the overexpression of those proteins might contribute to tumor angiogenesis and have prognostic value in tongue cancer.     

Bladder transitional cell carcinoma: correlation of contrast enhancement on computed tomography with histological grade and tumour angiogenesis

AIM: To investigate the correlation between the degree of contrast enhancement of bladder cancer in the early enhanced phase of helical computed tomography (CT) and microvessel density (MVD), vascular endothelial growth factor (VEGF) and histological grade. MATERIALS AND METHODS: Sixty-five patients with transitional cell carcinoma of the bladder were examined by incremental unenhanced CT and helical CT at 40-45 s after initiation of intravenous administration of contrast medium before surgery. The CT density in Hounsfield units of bladder carcinomas were measured in the middle of the maximum diameter section of the cancer lesions on unenhanced and enhanced CT. The degree of contrast enhancement of the tumour was determined as the absolute increase in Hounsfield units. Histological grade, VEGF and MVD were analysed for each cancer. The Pearson and Spearman correlation tests were used to determine the strength of the relationships between CT enhancement and histological grade, VEGF expression and MVD. RESULTS: Different degrees of enhancement were observed in 91 cancers during the early enhanced phase of helical CT. Mean MVDs and mean CT enhancing values of different histological grade groups were statistically different (p < 0.001). A positive correlation was found in the CT-enhancing value of bladder cancer and MVD (Pearson correlation test; r = 0.938, p < 0.001) and histological grade (Spearman rank correlation; r = 0.734, p < 0.001). VEGF of bladder cancer did not correlate with the change in CT attenuation (Spearman rank correlation; r = 0.087, p = 0.410) and MVD (Spearman rank correlation, r = 0.103, p = 0.330). CONCLUSION: In bladder cancer, the degree of contrast enhancement during the early enhanced helical CT is correlated with the MVD and histological grade of tumour. It is possible that MVD is the histopathological basis of early contrast enhancement of bladder cancer.     

三羧氨基喹啉对人口腔癌裸鼠移植瘤的抗血管生成作用与其调节巨噬细胞分泌细胞因子的关系

目的 :观察三羧氨基喹啉 ( Linom ide)对人口腔癌裸鼠移植瘤的治疗作用 ,探讨其抗血管生成作用与调节巨噬细胞分泌细胞因子的关系。方法 :建立人舌癌裸鼠移植瘤模型 ,观察 Linom ide对肿瘤生长的抑制作用 ,采用免疫组化染色检测 L inomide治疗组和对照组荷瘤裸鼠的肿瘤微血管密度 ( MV D)的变化 ,采用 ELISA方法检测Linom ide对巨噬细胞分泌促血管因子 TN F- α及血管抑制因子 G M- CSF功能的影响。结果 :10 0 m g/ kg· d- 1、50mg/ kg· d- 1Linom ide腹腔注射组、对照组裸鼠瘤重分别为 ( 0 .4 7± 0 .2 5) g、( 0 .92± 0 .30 ) g、( 1.75± 0 .38) g,治疗组瘤重明显降低 ( P<0 .0 1)。治疗组瘤组织 M VD明显减低 ,与对照组相比 ,50 m g/ kg· d- 1和 10 0 m g/ kg· d- 1Linom ide治疗组的 MV D分别减少了 38.2 %和 57.8%。 Linom ide治疗组腹腔巨噬细胞分泌 TN F-α的水平与对照组比较 ,受到明显抑制 ( P<0 .0 5)。 L inom ide体外处理小鼠巨噬细胞系 RA W 2 6 4.7也可明显抑制其分泌 TN F-α的水平 ( P <0 .0 5) ,并存在剂量效应关系。结论 :Linom ide可有效抑制人舌鳞状细胞癌裸鼠移植瘤的生长 ,降低肿瘤微血管密度 ,抑制巨噬细胞分泌 T NF-α可能是其一个重要的抗血管生成机制。     

静脉应用血管内皮生长因子治疗急性心肌梗死的实验研究

目的探讨静脉应用血管内皮生长因子（ＶＥＧＦ）是否对急性心肌梗死大鼠有利。方法３３只成年雄性ＳＤ大鼠，结扎左冠状动脉后２４ｈ随机接受ＶＥＧＦ－肝素（治疗组）或肝素－生理盐水（对照组）治疗。ＶＥＧＦ（２μｇ／ｍｌ）加肝素５０Ｕ）或肝素－生理盐水（５０Ｕ／ｍｌ）每天经尾静脉注射，共用７ｄ（治疗组ｎ＝８；对照组ｎ＝１０）和１４ｄ（治疗组ｎ＝７；对照组ｎ＝８）。于结扎后９ｄ和１６ｄ分别测定血认动力学参数、心     

角膜干细胞与角膜表层新生血管

从干细胞角度探讨角膜碱烧伤后表层新生血管的成因。对大鼠角膜缘部进行碱性烧灼造成不同程度的损害，连续观察5周，结果，缘部基底细胞完全破坏者，角膜以新生血管化愈合，而保留缘部基底细胞者，角膜无新生血管化。本实验进一步证实了角膜干细胞缘部基底层定位的观点，提示干细胞对碱性烧伤后阻止角膜的新生血管化，并重建角膜表面的完整性具有重要意义。     

Experimental omento-myelo-synangiosis

In 18 cats the omentum was mobilized, transposed, and placed directly upon the pia mater of the spinal cord. Within 2 months, vascular anastomoses developed at the omento-spinal cord interface and, as demonstrated by India ink perfusion, communicated widely with the cord's intramedullary vessels. Light and scanning electron microscopy (SEM) of the interface revealed the development of a “fibrous coat” of Goldsmith in continuity with the edges of the dura mater. It consisted mainly of a matrix of collagen fiber and fibroblasts, well vascularized with sinusoids, capillaries, arterioles and venules. The sinusoids, as identified by SEM, were present in both the fibrous coat and adjacent omentum, were lined with attenuated endothelium, and had multiple communications. The possible significance of the sinusoidal formation is discussed in this report.