Effect of vascular endothelial growth factor on skin graft survival in Sprague-Dawley rats

OBJECTIVE: To examine the effect of exogenous vascular endothelial growth factor (VEGF) on skin graft survival in Sprague-Dawley rats. DESIGN: Dorsal full-thickness skin grafts were harvested from 18 Sprague-Dawley rats. To simulate human full-thickness skin grafts, the panniculus carnosus muscle was removed from the undersurface of each graft. The recipient beds were delivered subfascial injections of recombinant human VEGF or isotonic sodium chloride solution in 12 animals before replacement of the grafts (6 in each group). Grafts were replaced without injections in 6 sham control animals. Using planimetry, grafts were analyzed for necrosis along epidermal and dermal surfaces on postoperative day 7. Results were compared between groups. To determine the role of the panniculus carnosus muscle in graft survival, 12 Sprague-Dawley rats underwent the same procedure with an intact panniculus carnosus muscle and with subfascial injections of VEGF or physiologic isotonic sodium chloride solution (6 in each group). Analyses were performed on postoperative day 14. The mean microvascular density was determined in each graft after staining with anti-factor VIII antibody. RESULTS: The mean percentage of dermal necrosis in VEGF-treated skin grafts (10.0%) was significantly lower than that in saline-treated grafts (26.7%) or in control grafts (18.9%). Reduced, but not significant, epidermal necrosis was found in VEGF-treated rats vs saline-treated rats. No difference was found in VEGF-treated grafts vs saline-treated grafts when the panniculus carnosus muscle was left intact. Increased microvascular density was observed in VEGF-treated grafts vs saline-treated grafts, which did not reach statistical significance (P = .17). CONCLUSION: Exogenously administered VEGF may improve the outcome of full-thickness skin grafts by decreasing dermal necrosis.     

鼻息肉中血管内皮生长因子和转化生长因子β1的表达

目的探讨血管内皮生长因子/血管通透性因子(vascular endothelial growth factor/vasular permeability factor,VEGF/VPF)和转化生长因子β1(transforminggrowth factor-β1 ,TGF-β1)在鼻息肉组织中的表达及意义。方法 34例鼻息肉标本及30例中鼻甲粘膜标本行VEGF/VPF及TGF-β1的免疫组化染色,光镜观察。结果①VEGF/VPF在鼻息肉组织的血管内皮细胞和腺体细胞的表达明显高于中鼻甲组织(P＜0.01和P＜0.05);②TGF-β1在鼻息肉组织的细胞外基质和固有层浸润细胞的表达明显高于中鼻甲组织(P＜0.005);③鼻息肉组织中TGF-β1阳性细胞的形态及分布相似于嗜酸粒细胞;④VEGF/VPF与TGF-β1阳性表达与鼻息肉的临床分型无关(P＞0.05)。结论①VEGF/VPF对鼻息肉发生过程中组织极度水肿的产生可能有非常重要的作用;②TGF-β1可能直接参与鼻息肉的病理变化,导致上皮基底膜增厚和基质纤维化;③嗜酸粒细胞可能为鼻息肉中TGF-β1的主要来源。     

Serum vascular endothelial growth factor in patients with head and neck squamous cell carcinoma.

Vascular endothelial growth factor (VEGF) is a key pro-angiogenic cytokine expressed by most human tumours. Two isoforms, VEGF121 and VEGF165, are soluble and can be assayed in serum. Serum VEGF has been shown to be significantly raised in patients with solid tumours and shows some promise as a potentially useful tumour marker. Serum levels of VEGF were assayed in 52 patients with untreated head and neck squamous cell carcinoma (HNSCC) and 104 healthy controls. Serum VEGF is significantly raised in patients with HNSCC (P < 0.001), but there was no association with either tumour stage or specifically the presence of nodal metastases. Sixteen patients (31%) had a higher serum VEGF than 95th centile of controls, suggesting that serum VEGF measurement is of little practical use as an initial diagnostic tool. The finding that patients with HNSCC have significantly raised serum VEGF probably relates to enhanced platelet aggregation in these patients.     

表皮生长因子受体及血管内皮生长因子在喉乳头状瘤中的表达

目的探讨表皮生长因子受体（EGFR）和血管内皮生长因子（VEGF）在喉乳头状瘤（IJP）中的表达及意义。方法采用免疫组化二步法检测10例成人型喉乳头状瘤（ALP）、19例幼年型喉乳头状瘤（JLP）石蜡标本中EGFR、VEGF的表达与分布;并以10例声带息肉作为对照组。结果EGFR和VEGF在ALP、JLP组上皮层的表达水平明显高于对照组（P〈0．05）。EGFR在ALP、JLP表皮组织全层均有强阳性表达,VEGF呈现以基底层、棘层细胞显著表达,到颗粒层表达逐渐减弱的模式。VEGF在ALP、JLP和对照组间质的血管内皮细胞、炎症细胞、成纤维细胞中也有表达,但3组问VEGF的表达元显著统计学差异（P〉0．05）。JLP组上皮中VEGF的表达评分结果（7．133±0．061）比ALP组（6．934±0．041）高,两组比较有统计学意义（P〈0．05）。结论VEGF、EGFR在LP组织中的过度表达可能在LP的上皮细胞过度增生和血管大量形成中发挥重要作用,JLP比ALP具有更强的增殖活性。     

Serum vascular endothelial growth factor in patients with head and neck squamous cell carcinoma

Vascular endothelial growth factor (VEGF) is a key pro-angiogenic cytokine expressed by most human tumours. Two isoforms, VEGF₁₂₁ and VEGF₁₆₅, are soluble and can be assayed in serum. Serum VEGF has been shown to be significantly raised in patients with solid tumours and shows some promise as a potentially useful tumour marker. Serum levels of VEGF were assayed in 52 patients with untreated head and neck squamous cell carcinoma (HNSCC) and 104 healthy controls. Serum VEGF is significantly raised in patients with HNSCC (P < 0.001), but there was no association with either tumour stage or specifically the presence of nodal metastases. Sixteen patients (31%) had a higher serum VEGF than 95th centile of controls, suggesting that serum VEGF measurement is of little practical use as an initial diagnostic tool. The finding that patients with HNSCC have significantly raised serum VEGF probably relates to enhanced platelet aggregation in these patients.     

Vascular and epidermal effects of fibroblast growth factor on irradiated and nonirradiated skin flaps

Head and neck cancer surgeons are often faced with the challenge of managing previously irradiated soft tissue that has poor vascularity and slower epithelialization. This study investigates the effect of supplemental basic fibroblast growth factor (bFGF) on flap vascularity, tissue oxygenation, and epidermal regeneration in nonirradiated (n = 40) and irradiated porcine skin flaps (n = 40). Supplemental bFGF increased vascularity in nonirradiated flaps by 80% (p = .005), with a trend to a higher tissue oxygen level by day 14. The irradiated bFGF-treated flaps did not show increased vascularity or higher tissue oxygen levels 2 weeks after surgery. However, in both irradiated and nonirradiated groups, epidermal regeneration increased by greater than 70% with supplemental bFGF (p < .002). The results of this study suggest that supplemental bFGF can increase tissue vascularity in nonirradiated tissues and epidermal regeneration in both nonirradiated and irradiated conditions.     

Expression of vascular endothelial growth factor and basic fibroblast growth factor in sporadic vestibular schwannomas correlates to growth characteristics.

HYPOTHESIS: Expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) may have an impact on the growth characteristics of sporadic vestibular schwannomas (VSs). BACKGROUND: Vestibular schwannoma is a benign, slow-growing neoplasm that accounts for 6% of all intracranial tumors. The biological backgrounds for neoplastic growth and especially for the various growth patterns of VS remain largely unknown. Because several angiogenic and cytotrophic factors have been described to be involved in the growth of malignant tumors, we initiated this study to examine 2 major representatives of such growth factors in VS and their possible correlation to the growth characteristics of sporadic VSs. METHODS: Surgical specimens from 17 patients with sporadic VS were examined, and the expression of 2 major angiogenic and neurotrophic factors, bFGF and VEGF, was quantitatively analyzed at the mRNA and protein levels. The microvessel density (MVD) was defined by CD31 staining. RESULTS: All tumors showed expression of bFGF and VEGF at both the mRNA and protein levels. The mRNA expression and the protein expression of both growth factors correlated positive to tumor volume, to tumor growth index, and to MVD. CONCLUSION: The bFGF and VEGF mRNA expression and the bFGF and VEGF protein expression in sporadic VS correlates to the tumour volume, to the tumor growth index, and to the MVD. This might indicate an angiogenic and neurotrophic influence of these factors and a possible involvement in the growth of sporadic VS.     

Expression of vascular endothelial growth factor receptors on tumor cells in head and neck squamous cell carcinoma

BACKGROUND: Angiogenesis is essential for the growth of solid tumors, including head and neck squamous cell carcinoma (HNSCC). Angiogenesis is regulated by angiogenic factors such as vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFRs) 1, 2, and 3 known to be located on vascular endothelial cells (VECs). We hypothesize that VEGFRs are also expressed on HNSCC tumor cells in vitro and in vivo and likely control tumor function in vivo. DESIGN: Immunohistochemical analysis for VEGFR-1 (n = 13), VEGFR-2 (n = 21), and VEGFR-3 (n = 16) was performed on human HNSCC tumor samples. Specimens were analyzed for receptor expression and staining intensity. A cultured oral SCC cell line (SCC-25) and a pharyngeal SCC cell line (FADU) were also studied for receptor expression. RESULTS: The HNSCC tumor cells expressed VEGFR-1, VEGFR-2, and VEGFR-3 in all specimens evaluated. Staining for all 3 receptors was also found on tumor-associated macrophages and fibroblasts, except that VEGFR-2 was not present on fibroblasts. Staining intensity for VEGFR-1 and VEGFR-2 was significantly higher in tumor cells and macrophages than in VECs stained for the same receptor. Both cultured HNSCC cell lines demonstrated expression of all 3 receptors. CONCLUSIONS: This represents the first report of all 3 VEGFRs being expressed by HNSCC cells. These findings indicate that VEGF may be an autocrine regulator of tumor cell activity in addition to its known angiogenic effects on VECs. The presence of VEGFRs on tumor-associated macrophages and fibroblasts contributes to the complexity of the VEGF/VEGFR system in human cancer.     

γ-干扰素对喉癌细胞血管内皮生长因子-C表达的影响

目的:研究γ-干扰素(IFN-γ)对人喉癌细胞株Hep-2细胞血管内皮生长因子-C(VEGF-C)基因及蛋白表达的影响.方法:将IFN-γ以不同浓度(103、104、105、106、107U/L)、不同作用时间(0、12、24、36、48、60、72 h)作用于Hep-2细胞,用四甲基偶氮唑蓝(MTT)比色法测定细胞增殖;用实时荧光定量PCR(Realtime-PCR)法测定IFN-γ(105U/L)不同作用时间(0、2、6、12、24、36、48、60、72 h)细胞VEGF mRNA含量;用双抗体夹心酶联免疫吸附试验、Western blot法和免疫细胞化学方法测定与Realtime-PCR相同药物浓度和作用时间细胞培养上清液和细胞质中VEGF-C蛋白含量.结果:①细胞生长受到抑制,以高浓度组表现最为明显;②不同浓度(103、104、105、106、107U/L)IFN-γ作用不同时间(0、12、24、36、48、60、72 h)后,从48 h开始,105、106、107U/L的IFN-γ对Hep-2细胞有明显的抑制作用,差异有统计学意义(P＜0.05),但不随着浓度的增加而成正比;③106U/L IFN-γ作用后,在36 h后与对照组比,VEGF-C mRNA表达下调,差异有统计学意义(P＜0.05),特别是48 h(P＜0.01);④104U/L IFN-γ作用36 h后,Western blot显示细胞中VEGF-C蛋白含量显著下降;⑤106U/L IFN-γ作用48 h后,与对照组相比,Hep-2细胞质中的棕色颗粒明显减少.结论:IFN-γ可以在核酸和蛋白质水平下调Hep-2细胞分泌VEGF-C.     

血管内皮生长因子及受体在喉癌细胞Hep-2中的表达及意义

目的:探讨血管内皮生长因子(VEGF)及受体Flt1和KDR在喉癌细胞Hep2中的表达及其与喉癌细胞的生长、浸润及转移的关系。方法:培养Hep2和Hacat细胞,提取总细胞RNA,应用RTPCR方法检测VEGFmRNA在Hep2和Hacat细胞中的表达;Flt1mRNA和KDRmRNA在Hep2细胞中的表达。结果:VEGFmRNA在Hep2细胞中高表达,在Hacat细胞中低表达,其差异有统计学意义(P<0.01)。在Hep2细胞中有flt1mRNA表达,平均积分吸收度(A值)为0.73886±0.13779;未检测到KDRmRNA表达。结论:VEGF及其受体与喉癌细胞的生长、浸润及转移有密切关系。     

缺氧对鼻息肉上皮细胞表达血管内皮生长因子的影响

目的　通过上皮细胞对缺氧和炎性因子刺激的主动应答作用 ,探讨上皮细胞和缺氧对鼻息肉早期形成的影响。方法　将鼻息肉及下鼻甲的上皮细胞分别在常氧和缺氧状态下 ,以及不同炎性因子刺激条件下进行无血清原代上皮细胞的培养 ,采用原位杂交 ,酶联免疫吸附测定 (enzyme linkedimmunosorbentassay ,ELISA)的方法 ,用促红细胞生成素 (erythropoietin ,EPO)为缺氧标志 ,检测上皮细胞分泌合成的血管内皮生长因子 (vascularendothelialgrowthfactor ,VEGF)的线粒体RNA(mitochondriaRNA ,mRNA)和蛋白质水平的变化。结果　①缺氧条件下 ,EPO在来自于鼻息肉和下鼻甲的上皮细胞中明显表达 ,且两者无明显差异 ,表明EPO可作为组织缺氧标志 ;②上皮细胞合成的VEGFmRNA的能力在各种刺激下增加 ,而以缺氧条件下增加最为明显 (P <0 0 0 1) ,其中鼻息肉的合成能力要强于下鼻甲 (P <0 0 1) ;③VEGF的蛋白质表达水平在不同的炎性因子以及缺氧刺激下表达增加 (P <0 0 1) ,且随作用时间的延长而增强。其中以缺氧刺激下升高最为明显 (P <0 0 0 1)。鼻息肉的表达明显高于下鼻甲 (P <0 0 1)。结论　上皮细胞在缺氧时可主动合成VEGF。而这种中鼻道黏膜缺氧诱导的VEGF的产生和分泌是鼻息肉早期形成的重要机制。这也可能是鼻息     

Effect of recombinant vascular endothelial growth factor on experimental otitis media with effusion

Conclusion This study demonstrates that rVEGF in the middle ear cavity contributes significantly to the development of OME by increasing the vascular permeability of the middle ear mucosa. Objective Vascular endothelial growth factor (VEGF) has been detected in otitis media with effusion (OME). It has a very strong effect on increasing vascular permeability, and is much more potent than platelet-activating factor, arachidonic acid metabolites or histamine. The purpose of this study was to investigate whether recombinant VEGF (rVEGF) can increase vascular permeability in the middle ear mucosa of rats. Material and methods rVEGF was injected transtympanically at doses of 0.01, 0.1 and 1.0 μg in the experimental groups; normal saline was injected in the control group. Twenty-four h after the injection of rVEGF, middle ear fluid was aspirated and the vascular permeability of the middle ear mucosa was measured by means of the Evans Blue vital dye technique. Results Extravasation of Evans Blue dye was found in all specimens injected with rVEGF, and was quantified using a spectrophotometer. Middle ear fluid developed in all ears injected with 0.1 or 1.0 μg of rVEGF and histopathology of the middle ear mucosa revealed severe inflammatory cellular infiltration, subepithelial edema and vascular dilatation. Rats injected with 1.0 μg of rVEGF showed a significant increase in middle ear vascular permeability in comparison with the control group (p<0.05).     

喉癌组织血管内皮生长因子的表达与喉癌临床病理关系

目的 :探讨血管内皮生长因子 (VEGF)的表达与喉鳞状细胞癌的临床病理关系。方法 :采用SP免疫组织化学染色技术 ,评价 87例喉鳞癌患者的肿瘤组织中VEGF的表达和微血管计数 (MVC)。资料分析采用SAS软件。结果 :在喉鳞状细胞癌中 ,VEGF的免疫反应主要发生于肿瘤细胞的胞浆内 ,其阳性率为 77.0 %。肿瘤侵犯范围越广 ,VEGF的表达越强 ,肿瘤侵犯范围越小 ,VEGF的表达越弱 (P <0 .0 5 ) ;肿瘤分化越差 ,VEGF的表达越强 ,肿瘤分化越好 ,VEGF的表达越弱 (P <0 .0 5 ) ;VEGF的表达越强 ,MVC越多 ,二者呈明显的正相关(P <0 .0 1) ,且肿瘤组织中的平均MVC明显高于切缘组织中的平均MVC(P <0 .0 1)。结论 :在喉鳞状细胞癌中 ,VEGF的表达与肿瘤的临床分期和分化明显相关 ,与MVC存在着明显的正相关 ,提示VEGF在喉鳞状细胞癌的进展中具有重要的作用     

血管内皮生长因子在鼻内翻性乳头状瘤中的表达

目的：明确血管内皮生长因子（ＶＥＧＦ）及其受体在鼻内翻性乳头状瘤（ＮＩＰ）组织中的探讨其在ＮＩＰ发病中的作用。方法：采用免疫组化ＳＰ法,对１１例ＮＩＰ标本及６例慢性单纯性鼻炎患者的下鼻甲标本,检测ＶＥＧＦ及其胎肝激酶受体,以图像分析仪半定量测定ＶＥＧＦ和ｆｌｋ－１的表达强度。     

Effect of recombinant vascular endothelial growth factor on experimental otitis media with effusion

CONCLUSION: This study demonstrates that rVEGF in the middle ear cavity contributes significantly to the development of OME by increasing the vascular permeability of the middle ear mucosa. OBJECTIVE: Vascular endothelial growth factor (VEGF) has been detected in otitis media with effusion (OME). It has a very strong effect on increasing vascular permeability, and is much more potent than platelet-activating factor, arachidonic acid metabolites or histamine. The purpose of this study was to investigate whether recombinant VEGF (rVEGF) can increase vascular permeability in the middle ear mucosa of rats. MATERIAL AND METHODS: rVEGF was injected transtympanically at doses of 0.01, 0.1 and 1.0 microg in the experimental groups; normal saline was injected in the control group. Twenty-four h after the injection of rVEGF, middle ear fluid was aspirated and the vascular permeability of the middle ear mucosa was measured by means of the Evans Blue vital dye technique. RESULTS: Extravasation of Evans Blue dye was found in all specimens injected with rVEGF, and was quantified using a spectrophotometer. Middle ear fluid developed in all ears injected with 0.1 or 1.0 microg of rVEGF and histopathology of the middle ear mucosa revealed severe inflammatory cellular infiltration, subepithelial edema and vascular dilatation. Rats injected with 1.0 microg of rVEGF showed a significant increase in middle ear vascular permeability in comparison with the control group (p < 0.05).