血管内皮生长因子对哺乳动物生殖的调节

睾丸间质细胞和支持细胞产生的血管内皮生长因子 ( VEGF)可能以旁分泌形式调节精子发生的微环境并影响精子发生。VEGF可能影响卵泡内血管通透性和血管发生 ,并参与排卵过程。胚胎着床期着床胚泡处的腔上皮细胞和腔上皮下的基质细胞中 VEGF表达明显增加。子宫增殖期间 VEGF表达的不断增加和 VEGF受体 2的高表达可能与月经后子宫内膜重建时快速的毛细血管增生有关。     

血管内皮细胞生长因子在急性肺损伤中的作用

急性肺损伤(acute lurg injury,ALI)和急性呼吸窘迫综合征(acute respiratory distressyndrome,ARDS)的特征性病理改变为肺毛细血管通透性增高所致的肺水肿,血管内皮细胞生长因子能抗血管内皮细胞凋亡并增加血管通透性,可能在ALI和ARDS的病理过程中起到重要作用.现对血管内皮细胞生长因子在ALI中的作用进行综述,旨在为ALI和ARDS的治疗提供新的思路.     

血管内皮生长因子与治疗性血管生成研究进展

血管内皮生长因子(vascular endothelial growtll factor,VEGF)是内皮细胞特异的有丝分裂原,有促进内皮细胞增生、增强血管通透性、加速新血管形成的作用.血管生成是一个具有重要生理、病理意义的过程.在人体的创伤愈合、炎症反应、器官再生过程以及肿瘤生长转移、血管增生性疾病中,血管生成有重要作用.治疗性血管生成是指利用成血管诱导因子或内皮祖细胞,模拟体内血管生成机制,促进新生血管形成,改善侧支循环.本文就VEGF和治疗性血管生成研究进展做一综述.     

血管内皮生长因子与治疗性血管生成

近年来 ,由于分子生物学等基础学科的迅猛发展 ,缺血性及其相关疾病的治疗取得了长足的进步。其中 ,以增加新生血管、改善缺血为主要目的的治疗性血管形成 (ｔｈｅｒａｐｅｕｔｉ ｃａｌａｎｇｉｏｇｅｎｅｓｉｓ)广泛地应用在各类缺血及其相关性疾病的实验和临床研究中。血管形成 (ａｎｇｉｏｇｅｎｅｓｉｓ)在机体的生长发育、新陈代谢、脏器修复、创伤愈合和生殖过程中均起着重要作用[1] ,有很多因素与之有关 ,其中 ,血管内皮细胞生长因子(ｖａｓｃｕｌａｒｅｎｄｏｔｈｅｌｉａｌｇｒｏｗｔｈｆａｃｔｏｒ,ＶＥＧＦ)的作用最为突出 ,尤…     

Vascular endothelial growth factor transgene expression in cell-transplanted hearts

OBJECTIVE: We evaluated the effect of transplanted cell type, time, and region of the heart on transgene expression to determine the potential of combined gene and cell delivery for myocardial repair. METHODS: Lewis rats underwent myocardial cryoinjury 3 weeks before transplantation with heart cells (a mixed culture of cardiomyocytes, smooth muscle cells, endothelial cells and fibroblasts, n = 13), vascular endothelial growth factor-transfected heart cells (n = 13), skeletal myoblasts (n = 13), vascular endothelial growth factor-transfected skeletal myoblasts (n = 13), or medium (control, n = 12). Vascular endothelial growth factor expression in the scar, border zone, and normal myocardium was evaluated at 3 days and at 1, 2, and 4 weeks by means of quantitative polymerase chain reaction. Transplanted cells and vascular endothelial growth factor protein were identified immunohistologically on myocardial sections. RESULTS: Vascular endothelial growth factor levels were very low in control scars but increased transiently after medium injection. Transplantation with heart cells and skeletal myoblasts significantly increased vascular endothelial growth factor expression in the scar and border zone. Transplantation of vascular endothelial growth factor-transfected heart cells and vascular endothelial growth factor-transfected skeletal myoblasts further augmented vascular endothelial growth factor expression, resulting in 4- to 5-fold greater expression of vascular endothelial growth factor in the scar at 1 week. Peak vascular endothelial growth factor expression was greater and earlier in vascular endothelial growth factor-transfected heart cells than in vascular endothelial growth factor-transfected skeletal myoblasts. Vascular endothelial growth factor was primarily expressed by the transplanted cells. Some of the transplanted heart cells and vascular endothelial growth factor-transfected heart cells were identified in the endothelial layer of blood vessels in the scar. CONCLUSIONS: Transplantation of heart cells and skeletal myoblasts induces vascular endothelial growth factor expression in myocardial scars and is greatly augmented by prior transfection with a vascular endothelial growth factor transgene. Vascular endothelial growth factor expression is limited to the scar and border zone for 4 weeks. Both heart cells and skeletal myoblasts may be excellent delivery vehicles for cell-based myocardial gene therapy.     

Vascular endothelial growth factor in chronic rat allograft nephropathy

BACKGROUND: Chronic allograft nephropathy (CAN) is a complex process of alloimmune responses and chronic inflammation leading to fibrosis and vasculopathy. We examined the biological role of proinflammatory vascular endothelial growth factor (VEGF) in a rat renal transplantation model of CAN. METHODS: Syngraft and allograft recipients were treated with a suboptimal dose of cyclosporine A which allows acute rejection and CAN to develop. Intragraft VEGF, VEGFR-1 and VEGFR-2 expressions were determined at 5, 14, 30 and 60 days. Protein tyrosine kinase inhibitor PTK787 was used to inhibit VEGFR activity. RESULTS: In nontransplanted kidneys and syngrafts, mild VEGF expression was observed in the glomeruli and tubuli. VEGFR-1 was detected in vascular structures and VEGFR-2 in glomeruli as well. In allografts, total intragraft VEGF expression and interstitial inflammatory cell VEGF expression were induced and correlated with the chronic allograft damage index (CADI) score. Total intragraft and interstitial inflammatory cell VEGFR-1 expression was induced and interstitial cell VEGFR-1 expression correlated with the CADI score. Blocking VEGF receptor signaling with PTK787 significantly reduced fibrosis and the CADI score, but did not affect early inflammation or VEGF, VEGFR-1, VEGFR-2 expressions compared to vehicle treated group. CONCLUSIONS: Interstitial inflammatory cell VEGF and VEGFR-1 expressions are induced during the development of CAN. Increased VEGF activity may enhance the alloimmune induced inflammatory responses leading to fibrosis and CAN.     

Vascular endothelial growth factor as prognostic factor in renal cell carcinoma

PURPOSE: Vascular endothelial growth factor (VEGF) has been recognized as an important constituent of vascularization and growth of solid tumors. Serum VEGF levels were evaluated and correlated to clinicopathologic findings and clinical outcome in patients with renal cell carcinoma (RCC). MATERIALS AND METHODS: Serum samples were collected before surgery in 164 patients with RCC. Levels of VEGF165 protein in sera were measured using a quantitative ELISA. Univariate and multivariate analyses were performed. RESULTS: The VEGF165 level in serum was significantly increased (p = 0.0001) in patients with RCC (median 343.4 pg./ml.) compared with the control patients (median 103.8 pg./ml.). The level of VEGF165 in serum correlated to clinical stage and histopathological grade. Patients with VEGF165 levels below median value had significantly longer survival time than patients with higher levels (p = 0.0001). This was also shown when VEGF165 was analyzed in univariate Cox regression (p = 0.0001). The impact of VEGF165 on survival was especially shown in patients having tumors with vein invasion (pT3b-c N0 M0) and in patients with clinical stages I - III (p = 0.0240 and p = 0.0023, respectively). When using multivariate analysis, only tumor stage and grade remained as independent prognostic variables. CONCLUSIONS: In RCC, serum VEGF165 level was significantly correlated to tumor stage and grade. Increased levels were correlated to adverse survival. Although, VEGF did not remain as an independent prognostic factor in multivariate analysis the levels of VEGF165 in serum was found useful for the identification of patients with potentially progressive disease especially for those with vein invasion.     

血管内皮生长因子与结直肠癌关系研究进展

血管内皮细胞生长因子是启动血管形成的一种高度特异的有丝分裂原，是强有力的肿瘤生长促进因子，与结直肠癌的血管发生、肿瘤进展、预后、转移以及治疗均有密切关系。     

Treatment of Ewing's sarcoma in the cooperative Ewing's sarcoma study group

Multidisciplinary treatment approaches have greatly improved the prognosis of patients with Ewing's sarcoma. Four- or five-drug combination chemotherapy regimens are combined with radiation and/or surgery for local control. Currently, in the Cooperative Ewing's Sancoma Study (CESS) trials, approximately 60% of the protocol patients with Ewing's sarcoma show a relapse-free 10-year survival. For improvement of local control, preoperative radiotherapy and/or brachytherapy may be helpful. The early detection of blood and/or bone marrow contamination by molecular diagnosis can lead to a new clinical staging system. A myeloablative regimen consisting of simultaneous total-body irradiation and chemotherapy may improve the prognosis of patients with disseminated disease.     

血管内皮生长因子在甲状腺癌的表达及意义

血管内皮生长因子特异性作用于血管内皮细胞,通过促进内皮细胞的增生,增加血管通透性,以诱导肿瘤血管及淋巴管生成,在肿瘤的发生发展中起到关键作用.研究表明,VEGF及其受体的表达与甲状腺癌的发生,淋巴结转移,预后密切相关,抑制VEGF及其受体的表达在甲状腺未分化癌及髓样癌的治疗中有一定的应用前景.     

Vascular endothelial growth factor in children with congenital heart disease

BACKGROUND: Children with cyanotic congenital heart disease may experience the development of abnormal vessels that become a source of significant morbidity. Abnormal vessel proliferation in these children may take several forms, including systemic-to-pulmonary collateral arteries, systemic-to-pulmonary venous collaterals, systemic venous collateral channels after bidirectional cavopulmonary anastomosis, and pulmonary arteriovenous malformations. However, no entity responsible for these abnormalities has been identified yet. This study determined whether children with cyanotic congenital heart disease have elevated serum levels of vascular endothelial growth factor (VEGF) and whether elevated VEGF correlated with these abnormal vessels. METHODS: Mean systemic room air oxygen saturation (SpO2), blood cell counts (RBC), and serum VEGF levels were measured preoperatively. Samples were obtained from 61 children with acyanotic heart disease (group N) and 102 children with cyanotic heart disease (group C) before cardiac surgery. Postoperative catheterization was performed 1-month after the operation to evaluate the abnormal vessels in group C. RESULTS: The VEGF level was significantly elevated in group C (355.0 +/- 287.1 pg/mL) compared with group N (203.0 +/- 221.6 pg/mL; p < 0.001). VEGF levels in patients with a single ventricle associated with asplenia syndrome (n = 7) in group C were significantly elevated (711.9 +/- 443.5 pg/mL) compared with other patients. There was no significant correlation between VEGF level and SpO2 or RBC. Abnormal vessels were diagnosed in 19.6% (20/102) patients in group C. There was no difference in VEGF levels between the patients with abnormal vessels (336.8 +/- 182.5 pg/mL) and the patients without abnormal vessels (359.1 +/- 306.8 pg/mL). CONCLUSIONS: Children with cyanotic heart disease have elevated systemic levels of VEGF, especially in those patients with a single ventricle associated with asplenia syndrome. There was no significant relationship in VEGF levels between the patients with abnormal vessels and without these vessels.