缺血性视网膜静脉阻塞继发黄斑水肿患者基线血清己糖激酶1抗体滴度与抗VEGF治疗后视力改善的相关性分析

目的分析缺血性视网膜静脉阻塞继发黄斑水肿(RVO-ME)患者基线血清己糖激酶1抗体滴度与抗血管内皮生长因子(VEGF)治疗后视力改善的相关性。方法招募2017年6月至2020年2月在首都医科大学宣武医院确诊为缺血性RVO-ME并接受初始抗VEGF治疗的53例患者,其中缺血性视网膜中央静脉阻塞(CRVO)23例(CRVO组),缺血性视网膜分支静脉阻塞(BRVO)30例(BRVO组)。另选取该院同期30例行超声乳化的白内障患者作为对照组。研究对象行基线血清己糖激酶1抗体滴度检测、眼科常规检查和光学相干断层成像(OCT)检查。所有RVO-ME患者按照“3+按需治疗方案(pro re nata,PRN)”向玻璃体内注射抗VEGF药物治疗。随访12个月,采用多元线性回归分析缺血性RVO-ME患者抗VEGF治疗后视力改善的影响因素。结果CRVO组基线logMAR BCVA高于对照组和BRVO组,CRVO组和BRVO组基线CRT、基线血清己糖激酶1抗体滴度高于对照组,且CRVO组基线CRT、基线血清己糖激酶1抗体滴度高于BRVO组,差异有统计学意义(P<0.05)。RVO-ME患者基线血清己糖激酶1抗体滴度与随访6个月(r=0.377,P=0.005)、9个月(r=0.362,P=0.008)和12个月(r=0.465,P<0.001)时BCVA改善呈正相关,与随访12个月时中断EZ横向长度减少值(r=0.401,P=0.001)呈正相关。多元线性回归分析结果显示,基线logMAR BCVA、基线血清己糖激酶1抗体滴度是缺血性RVO-ME患者抗VEGF治疗随访12个月时BCVA改善的影响因素(P<0.05)。结论己糖激酶1抗体作为一种新的血清生物标志物,与缺血性RVO-ME患者抗VEGF治疗后的视力改善相关。

The Effect of Simvastatin on mRNA Expression of Transforming Growth Factor-β1,Bone Morphogenetic Protein-2 and Vascular Endothelial Growth Factor in Tooth Extraction Socket

Aim To determine the effect of local simvastatin application on the mRNA expression level of transforming growth factor-β1 （TGF-β1）, bone morphogenetic protein-2 （BMP-2） and vascular endothelial growth factor （VEGF） in the tooth sockets of rat. Methodology Forty-eight male Wistar rats were randomly divided into experimental and control groups （n=24）. Polylactic acid/polyglycolic acid copolymer carriers, with or without simvastatin, were implanted into extraction sockets of right mandibular incisors. The expression of TGF-β1, BMP-2 and VEGF mRNA was determined by in situ hybridization in the tooth extraction socket at five days, one week, two weeks and four weeks after implantation. Results The fusiform stroma cells in the tooth extraction socket began to express TGF-β1, BMP-2 and VEGF mRNA in both experimental and control groups from one week after tooth extraction until the end of experiment. The expression of TGF-131 and BMP-2 mRNA in the experimental group was significantly up-regulated after one, two and four weeks, and expression of VEGF mRNA was significantly increased after one and two weeks compared with that in the control group. Conclusion The findings indicate that local administration of simvastatin can influence alveolar bone remodeling by regulating the expression of a school of growth factors which are crucial to osteogenesis in the tooth extraction socket.

Apelin and vascular endothelial growth factor are associated with mobilization of endothelial progenitor cells after acute myocardial infarction

This study was designed to determine the levels of early endothelial progenitor cells （EPCs）, apelin, vascu- lar endothelial growth factor （VEGF） and stromal cell-derived growth factor-1 （SDF-1） after acute myocardial infarction （AMI）, and to investigate the relationships between these cytokines and early EPCs. Early EPCs, de- fined as CD133＋, KDR＋, and CD34~ cells, were quantified by flow cytometry. The levels of early EPCs and those cytokines in AMI patients were significantly different from those with coronary artery disease or controls （P 〈 0.05）. Plasma apelin levels were inversely correlated with Gensini score and early EPCs （both P 〈 0.01）. Early EPCs, VEGF and SDF-1 showed different patterns of changes in AMI patients during the first 24 h. The trend in the change of early EPCs was proportionally correlated with that of VEGF （P 〈 0.05）. AMI patients exhibited in- creased early EPCs with remarkably decreased apelin levels and enhanced VEGF levels.

Serum Vascular Endothelial Growth Factor Levels in Patients with Non-small Cell Lung Cancer and Its Relations to the Micrometastasis in Peripheral Blood

To examine the relationship between the levels of the serum vascular endothelial growth factor （VEGF） and the micrometastasis of peripheral blood in patients with non-small cell lung cancer （NSCLC）, 108 NSCLC patients, including 40 patients with benign lung diseases and 30 healthy controls, were investigated. The serum VEGF levels were detected by ELISA and CK19 mRNA in peripheral blood by reverse transcriptase-polymerase chain reaction （RT-PCR）. In NSCLC group, the serum VEGF levels and the positive rate of CK19 mRNA in peripheral blood were 479.8±268.5 pg/mL and 66.7%, which were significantly higher than those of the other two groups respectively （P〈0.01）, and both of them were increased significantly with the progression of clinical stage of the tumors （P〈0.01）. Serum VEGF levels as well as the positive rate of CK19 mRNA in different pathological types of lung cancer had no significant differences （P〉0.05）. Serum VEGF levels in the patients positive for CK19 mRNA was 561.7±325.6 pg/mL. It is significantly higher than that in the negative patients （P〈0.01）. There existed a significant correlation between serum VEGF levels and expression of CK19 mRNA in peripheral blood in NSCLC patients （P〈0.001）. The detection of serum VEGF levels and CK19 mRNA in peripheral blood is helpful in judging the condition and the prognosis of NSCLC patients, and serum VEGF levels and CK19 mRNA are independent of the pathological types of lung cancer. The micrometastasis in peripheral blood of NSCLC patients is significantly associated with serum VEGF levels.

“手十二井穴”放血预处理对大鼠急性低氧肺组织损伤模型血气、HIF-1α及VEGF水平的影响

目的 观察“手十二井穴”放血预处理对大鼠急性低氧肺组织损伤模型血气相关指标、低氧诱导因子(HIF)-1α及血管内皮细胞生长因子(VEGF)表达的影响,探讨“手十二井穴”放血预处理对急性低氧肺组织损伤的影响。方法 将72只雄性SD大鼠随机分为对照组8只、低氧(模型)组32只、井穴放血预处理(放血)组32只,模型组和放血组又分为6、24、48、72 h 4个时间段亚组,每组各8只。采用实验动物低氧模拟舱模拟15%O_(2)浓度,制备大鼠急性低氧肺组织损伤模型。放血组按“少商”“商阳”“中冲”“关冲”“少冲”“少泽”的顺序,每天1次,共5 d。用手持式血气分析仪检测肺动脉血气氧分压(PaO_(2))、血氧饱和度(SaO_(2))、酸碱度(pH)、二氧化碳分压(PaCO_(2))等相关指标,采用Western印迹法检测HIF-1α表达,酶联免疫吸附试验(ELISA)法检测VEGF含量。结果 与对照组比较,模型组各时间段PaO_(2)、SaO_(2)明显降低,HIF-1α和VEGF表达水平显著升高(P<0.01)。与同时间段模型组比较,放血组PaO_(2)和SaO_(2)均出现升高,PaO_(2)在6、48 h时有统计学意义,SaO_(2)值在6、24、48 h时有统计学意义(P<0.05,P<0.01),HIF-1α表达在各时段明显下调,VEGF含量在24、48、72 h时明显下降(P<0.05,P<0.01)。但放血组PaO_(2)各时间段和SaO_(2)(6、24 h)仍低于对照组,HIF-1α(6、48、72 h)和VEGF各时间段表达水平仍高于对照组,差异有统计学意义(P<0.05,P<0.01)。结论 “手十二井穴”放血预处理在一定时间和程度上可改善大鼠急性低氧(15%O_(2),85%N_(2))肺组织损伤模型的缺氧情况,其可能的作用与升高动脉血PaO_(2)、SaO_(2)及下调HIF-1α表达、降低VEGF含量有关,从而有利于模型大鼠适应急性低氧环境。

Integrin binding peptides facilitate growth and interconnected vascular-like network formation of rat primary cortical vascular endothelial cells in vitro

Neovascularization and angiogenesis in the brain are important physiological processes for normal brain development and repair/regeneration following insults. Integrins are cell surface adhesion receptors mediating important function of cells such as survival, growth and development during tissue organization, differentiation and organogenesis. In this study, we used an integrin-binding array platform to identify the important types of integrins and their binding peptides that facilitate adhesion, growth, development, and vascular-like network formation of rat primary brain microvascular endothelial cells. Brain microvascular endothelial cells were isolated from rat brain on post-natal day 7. Cells were cultured in a custom-designed integrin array system containing short synthetic peptides binding to 16 types of integrins commonly expressed on cells in vertebrates. After 7 days of culture, the brain microvascular endothelial cells were processed for immunostaining with markers for endothelial cells including von Willibrand factor and platelet endothelial cell adhesion molecule. 5-Bromo-2′-dexoyuridine was added to the culture at 48 hours prior to fixation to assess cell proliferation. Among 16 integrins tested, we found that α5β1, αvβ5 and αvβ8 greatly promoted proliferation of endothelial cells in culture. To investigate the effect of integrin-binding peptides in promoting neovascularization and angiogenesis, the binding peptides to the above three types of integrins were immobilized to our custom-designed hydrogel in three-dimensional(3 D) culture of brain microvascular endothelial cells with the addition of vascular endothelial growth factor. Following a 7-day 3 D culture, the culture was fixed and processed for double labeling of phalloidin with von Willibrand factor or platelet endothelial cell adhesion molecule and assessed under confocal microscopy. In the 3 D culture in hydrogels conjugated with the integrin-binding peptide, brain microvascular endothelial cells formed interconnected vascular-like network with clearly discernable lumens, which is reminiscent of brain microvascular network in vivo. With the novel integrin-binding array system, we identified the specific types of integrins on brain microvascular endothelial cells that mediate cell adhesion and growth followed by functionalizing a 3 D hydrogel culture system using the binding peptides that specifically bind to the identified integrins, leading to robust growth and lumenized microvascular-like network formation of brain microvascular endothelial cells in 3 D culture. This technology can be used for in vitro and in vivo vascularization of transplants or brain lesions to promote brain tissue regeneration following neurological insults.

STI571 (Glivec) suppresses the expression of vascular endothelial growth factor in the gastrointestinal stromal tumor cell line,GIST-T1

AIM:To estimate whether STI571 inhibits the expressionof vascular endothelial growth factor(VEGF)in thegastrointestinal stromal tumor(GIST)cells.METHODS:We used GIST cell line,GIST-T1.It hasa heterogenic 57-bp deletion in exon 11 to produce amutated c-KIT,which results in constitutive activationof c-KIT.Cells were treated with/without STI571 orstem cell factor(SCF).Transcription and expression ofVEGF were determined by RT-PCR and flow cytometryor Western blotting,respectively.Activated c-KIT wasestimated by immunoprecipitation analysis.Cell viabilitywas determined by MTT assay.RESULTS:Activation of c-KIT was inhibited bySTI571 treatment.VEGF was suppressed at both thetranscriptional and translational levels in a temporal anddose-dependent manner by STI571.SCF upregulatedthe expression of VEGF and it was inhibited by STI571.STI571 also reduced the cell viability of the GIST-T1cells,as determined by MTT assay.CONCLUSION:Activation of c-KIT in the GIST-T1regulated the expression of VEGF and it was inhibited bySTI571.STI571 has antitumor effects on the GIST cellswith respect to not only the inhibition of cell growth,butalso the suppression of VEGF expression.

A fusion protein containing murine vascular endothelial growth factor and tissue factor induces thrombogenesis and suppression of tumor growth in a colon carcinoma model

Induction of tumor vasculature occlusion by targeting a thrombogen to newly formed blood vessels in tumor tissues represents an intriguing approach to the eradication of primary solid tumors. In the current study, we construct and express a fusion protein containing vascular endothelial growth factor (VEGF) and tissue factor (TF) to explore whether this fusion protein has the capability of inhibiting tumor growth in a colon carcinoma model. The murine cDNA of VEGF A and TF were amplified by reverse transcriptase polymerase chain reaction (RT-PCR), and then cloned into prokaryotic expression plasmid pQE30 with a linker. The expression product recombinant VEGF-TF (rVEGF-TF) was purified and proved to have comparable enzyme activity to a commercial TF and the capability of specific binding to tumor vessels. Significant decrease of tumor growth was found in the mice administered with rVEGF-TF on Day 6 after initiated rVEGF-TF treatment (P<0.05), and the tumor masses in 2 of 10 mice were almost disappeared on Day 14 after the first treatment. In addition, valid thrombogenesis and tumor necrosis were observed in the tumor tissues injected with rVEGF-TF. Our results demonstrate that occlusion of tumor vasculature with rVEGF-TF is potentially an effective approach for cancer therapy.

Evaluation of Serum and Aqueous Humor Vascular Endothelial Growth Factor in Neovascular Glaucoma

Purpose: The study aimed to evaluate and correlate between the levels of vascular endothelial growth factor (VEGF) in serum and aqueous humor in cases of neovascular glaucoma (NVG) to stand up on if it can be used as a marker for early detection of such cases. Methods: This observational case control study included 60 eyes, divided into 3 groups, group A of 30 eyes presented by cataract of different causes (not diabetic patients and no signs of NVG) as a control group and group B of 30 eyes with NVG due to different causes, group C of the same eyes in group B but after one month of treatment by intravitreal bevacizumab and laser treatment by pan retinal photocoagulation (PRP). Serum VEGF was estimated in all groups, also aqueous humor VEGF was estimated in group A and B only. In addition glycosylated hemoglobin (HbA1c) was estimated in group B;statistical analysis of the results was performed. Results: The study revealed that the commonest cause of NVG was proliferative diabetic retinopathy (PDR) in 26 cases (86.7%), HbA1c in group B revealed mean value 7.68% ± 2.75%. Serum VEFG level in the group B of cases of NVG was significantly higher than the control group A (P 0.05). Conclusions: VEGF is considered a good marker for the NVG either in serum or aqueous humor, laser treatment and the use of anti-VEGF are crucial treatment for such cases, and also glycemic control is a must for regulation of the vascular process in diabetic patients for prevention of such ocular neovascularization.

Interleukin-1α, 6 regulate the secretion of vascular endothelial growth factor A, C in pancreatic cancer

Vascular endothelial growth factor (VEGF, namely VEGF-A) is an angiogenic polypeptide and VEGF-C is a lymphangiogenic polypeptide that has been implicated in cancer growth, invasion and metastasis. Several cytokines and growth factors play an important part in cancer progression. These cytokines and growth factors are the principal mediators of cancer cells-stromal cell interaction , which is critical for invasion of cancer cells to the surrounding tissues and metastatic dissemination to distant organs. In this study, we studied VEGF-A, C expression in cultured human pancreatic cancer cell lines and whether the presence of VEGF-A, C in the cell lines is regulated by cytokines interleukin-lct (EL-1α), and interleukin-6 (IL-6). METHODS: We used Northern blot and Western blot methods to analyze expression of the gene and protein of VEGF-A, C in all 6 tested cell lines (ASPC-1, CAPAN-1, MIA-PaCa-2, PANC-1, COLO-357 and T3M4) respectively. To analyze what is the regulator for this VEGF-A, C expression in pancreatic cancer,we used the reverse transcription -polymerase chain reaction (RT-PCR) method to analyze VEGF-A, C expression in cultured human pancreatic cancer cell lines (CAPAN-1 and COLO-357) under the stimulation with IL-1α (10μg/L) or IL-6 (100 μg/L). RESULTS:Northern blot analysis revealed the presence of the 4.1-kb VEGF-A mRNA transcript and 2.4-kb VEGF-C mRNA transcript in all 6 tested cell lines. Immunoblotting with highly specific anti-VEGF-A, anti-VEGF-C antibody revealed the presence of a molecular weight of 43-kDa VEGF-A protein and 55-kDa VEGF-C protein in all the cell lines. RT-PCR analysis revealed the levels of the VEGF-A and VEGF-C gene were 1-2 fold and a 1-fold increase in the COLO-357 cell line by stimulation with IL-la, however, no effect was found in the CAPAN-1 cell line. The levels of the VEGF-A and VEGF-C gene were 2-5 fold and a 1-fold increase in the CAPAN-1 cell line by stimulation with IL-6, but, no effect was found in the COLO-357 cell line. CONCLUSION:These findings suggested that the expression of VEGF-A, C and their regulation by IL-1α, IL-6 in pancreatic cancer contributes to the lymphatic and distant metastasis and the disease progression.

Vascular endothelial growth factor induced angiogenesis following focal cerebral ischemia/reperfusion injury in rabbits

BACKGROUND： Therapeutic angiogenesis has opened up new pathway for the treatment of ischemic cerebrovascular disease in recent years. The exploration of the effect of vascular endothelial growth factor （VEGF） on inducing angiogenesis following ischemia/reperfusion injury can provide better help for the long-term treatment of cerebrovascular disease in clinic. OBJECTIVE： To observe the effect of VEGF on inducing angiogenesis following focal cerebral ischemia /reperfusion injury in rabbits through the angiogenesis of microvessels reflected by the expression of the factors of vascular pseudohemophilia. DESIGN： A randomized controlled animal tria SETTNG： Department of Medical Imaging, Second Hospital of Hebei Medical University MATERIALS： Sixty-five healthy male New Zealand rabbits of clean degree, weighing （2.6±0.2） kg, aged 4.5-5 months, were used. The polyclonal antibody against vascular pseudohemophilia （Beijing Zhongshan Company）, recombinant VEGF165 （Peprotech Company, USA）, biotinylated second antibody and ABC compound （Wuhan Boster Company） were applied. METHODS： The experiments were carried out in the Laboratory of Neuromolecular Imaging and Neuropathy, Second Hospital of Hebei Medical University from May to August in 2005. （1） The rabbits were randomly divided into three groups： sham-operated group （n=15）, control group （n=25） and VEGF-treated group （n=-25）. In the control group and VEGF-treated group, models were established by middle cerebral artery occlusion （MCAO） induced focal cerebral ischemia/reperfusion. In the VEGF-treated group, VEGF165 （2.5 mg/L） was stereotactically injected into the surrounding regions of the infarcted sites immediately after the 2-hour ischemia/reperfusion; Saline of the same dosage was injected in the control group. But the rabbits in the sham-operated group were only drilled but not administrated. （2） The experimental indexes were observed on the 3^rd 7^th, 14^th, 28^th and 70^th days of the experiment respectively, 3 rabbits in the sham-operated group and 5 in the control group and VEGF-treated group were observed at each time point. The brain tissues in the surrounding regions of the infarcted sites were collected. The positive expressions of the factors of vascular pseudohemophilia in vascular endothelial cells were analyzed with immunohistochemical method. The microvessels in unit statistical field were counted with the imaging analytical software. MAIN OUTCOME MEASURES： The changes of microvascular density in the brain tissue and the positive expressions of the factors of vascular pseudohemophilia in the surrounding regions of the infarcted sites were observed on the 3^rd 7^th, 14^th, 28^th and 70^th days of the experiment. RESULTS： All the 65 New Zealand rabbits were involved in the analysis of results without deletion. Changes of the number of microvessels at different time points in each group： There were no obvious changes at different time points in the sham-operated group. The numbers of microvessels at 7 and 14 days were obviously more in the control group than in the sham-operated group [（6.0±1.1）, （9.0±0.9） microvessels; （3.0±1.1）, （3.0±1.1） microvessels; P〈 0.05-0.01], and those at 3, 7, 14 and 28 days were obviously more in the VEGF-treated group than in the control group [（8.3±2.0）, （13.4±1.4）, （15.5±2.3）, （6.8± 1.0） microvessels; （3.4±0.6）, （6.0±1.1）, （9.0±0.9）, （3.2±0.8） microvessels; P 〈 0.01]. （2） Positive expressions of the factors of vascular pseudohemophilia in the surrounding regions of infarcted sites： There were no obvious changes at different time points in the sham-operated group. In the control group, the changing law of the expressions was the same as that for the number of microvessels that the expression began to mildly increase at 7 days, reached the peak value at 14 days, and began to reduce at 28 days. In the VEGF-treated group, the expression was obviously increased at 3 days, also reached the peak value at 14 days, and reduced to the normal level at 70 days, but the expressions were obviously stronger than those in the control group at the same time points. CONCLUSION： Angiogenesis can be obviously induced in rabbits after the focal cerebral ischemia/reperfusion injury is treated with VEGF for 18 days.

Vascular endothelial growth factor expression and significance in different grades of the Breast Imaging Reporting and Data System

Objective Mammography is the only modality proven to reduce mortality in breast cancer,and ultrasonography is a well-known adjunct to mammography screening.The Breast Imaging Reporting and Data System(BI-RADS) classification is a practical tool and is correlated with histopathology and combined use with triple assessment(examination,imaging,and biopsy) of palpable diagnostic cases.This study aimed to investigate the relationship between vascular endothelial growth factor(VEGF) expression and different grades of BI-RADS in breast cancer.Methods Ninety-six patients with breast carcinoma were evaluated using BI-RADS by ultrasonography,mammography,and a combination of both modalities.In the combined imaging assessment,BI-RADS 1-4a grade was considered when the score of ultrasonography and mammography was lower than 4a,and BI-RADS 4b-5a grade was considered when the score of ultrasonography and mammography was higher than 4a.Immunohistochemical Ultra SensitiveTM S-P method was employed to evaluate the expression of VEGF in 96 patients.Fifty patients with benign breast disease were selected as the control group.The relationship between VEGF expression and different grades of BI-RADS and that between VEGF expression and other standard prognostic parameters associated with invasive breast cancer,such as size,grade,cancer stage,and metastasis were analyzed.Results The sensitivities of ultrasonography and mammography alone was 74.0% and 84.4%,respectively;However,the sensitivity of their combination increased to 90.6%.The positive rates of VEGF in invasive breast cancer BI-RADS 4b-5(59/87,67.8%) were higher than those in BI-RADS 4a(3/9,33.3%,P<0.05) and benign breast disease tissues(BI-RADS 1-4a,11/50,22.0%)(P<0.05).There was a positive correlation between VEGF overexpression and BI-RADS 4b-5,histological grade(Ⅲ),lymph node metastasis,and distant metastasis of invasive breast cancer.VEGF expression was not related to the age and size of the tumor in each group(P>0.05).Conclusion There was a positive correlation between VEGF overexpression and BI-RADS 4b-5 grade.The overexpression of VEGF might be an important biological marker for the invasion and metastasis of breast cancer.

Variations in vascular endothelial growth factor levels during ovarian superovulation and reduction of ovarian hyperstimulation incidence in young women: A prospective study

Variations in Vascular Endothelial Growth Factor (VEGF) levels were prospectively evaluated in 18 young women undergoing in vitro fertilization treatments according to the “Long Protocol” and a typical pattern of VEGF levels was recorded. A significant increase in VEGF concentrations was observed only when the follicles reached a mean diameter of 15.3 mm in concurrence with mature oocyte retrieval. Since an increase in VEGF levels is related to follicular vascularity and oocyte developpment, our study supports the approach that oocyte retrieval may be performed when follicles > 15 mm in diameter appear. Anticipating egg retrieval in young patients with an optimal ovarian reserve may decrease the incidence of severe ovarian hyperstimulation, without compromising the treatment results.

Expression of Vascular Endothelial Growth Factor-C and Vascular Endothelial Growth Factor Receptor-3 in Ovarian Epithelial Tumors

Objective： To explore the role of vascular endothelial growth factor-C （VEGF-C） in the process of angiogenesis, lymphangiogenesis and lymphatic metastasis in epithelial ovarian tumors. Methods： In situ hybridization and immunohistochemical staining for VEGF-C were performed in 30 epithelial ovarian carcinomas, 9 borderline tumors and 26 benign tumors. Endothelial cells were immunostained with anti-VEGFR-3 pAb and anti-CD31 mAb, and VEGFR-3 positive vessels and microvessel density （MVD） were assessed by image analysis. Results： VEGF-C mRNA and protein expression were detected in cytoplasm of carcinoma cells. VEGF-C mRNA and protein expression in ovarian epithelial carcinomas were significantly higher than those in borderline tumors and benign tumors （P〈0.05 or P〈0.01）. In ovarian epithelial carcinomas, VEGF-C protein expression, VEGFR-3 positive vessels and MVD were significantly higher in the cases of clinical stage Ⅲ-Ⅳ and with lymph node metastasis than those of clinical stage Ⅰ-Ⅱ and without lymph node metastasis respectively （P〈0.05 or P〈0.01）. VEGFR-3 positive vessels and MVD were significantly higher in VEGF-C protein positive tumors than negative tumors （P〈0.05）. VEGFR-3 positive vessels was significantly correlated with MVD（P〈0.01）. Conclusion： VEGF-C might play a role in lymphatic metastasis via lymphangiogenesis and angiogenesis in epithelial ovarian tumors, and VBEGF-C could be used as a biologic marker of metastasis in ovarian epithelial tumors.

Anti-vascular endothelial growth factor treatment for retinopathy of prematurity

Retinopathy of prematurity(ROP)is a proliferative disorder of the developing retina in premature and low birth weight infants.Recently,the role of vascular endothelial growth factor(VEGF)in the pathophysiology of ROP has been well studied and anti-VEGF drugs have been used in phase 2 to treat ROP patients in many ways.At first,ophthalmologists began to give intravitreal bevacizumab(IVB)or ranibizumab off-label to treat ROP as a salvage treatment after failure in laser photocoagulation or in combination with laser as an adjuvant treatment for patients had media opacity or rigid pupil.Now anti-VEGF drugs are also used as monotherapy in type I ROP or perioperative use in stage 4/5 ROP.Questions remain regarding long-term safety,dose,timing,visual outcomes and long-term effects,including systemically.

The predictive value of vascular endothelial growth factor and Ki-67 expression on neoadjuvant therapy in rectal cancer

调查脉管的内皮生长因素(VEGF ) 和增殖的房间的表情的目的在有直肠的腺癌的病人和他们有 neoadjuvant 的协会的原子抗原(Ki-67 ) 治疗。方法包括两预告的处理肿瘤活体检视和手术后的标本，在直肠的腺癌的 32 种情况中的 Ki-67 和 VEGF 的表情被免疫组织化学用特定的抗体检测，并且与 clinicopathological 因素被相关。结果染色的 VEGF 的紧张显著地与淋巴被相关节的转移( P = 0.033 )，肿瘤侵略的深度( P = 0.007 )并且肿瘤舞台( P = 0.016 )，然而并非与组织学的类型，肿瘤尺寸，病人的年龄和性( P 】 0.05 )。VEGF 表示的底层与对 neoadjuvant 治疗的反应的高敏感有重要关联(P = 0.016 ) 。VEGF 表示的短暂增加能在 neoadjuvant 治疗以后被看见(P = 0.035 ) 。把索引(Ki-67-LI ) 标记的 Ki-67 显著地与淋巴节点转移被相关(P = 0.028 ) ，然而并非相关到肿瘤尺寸，病人的年龄和性(P 】 0.05 ) 。有更低的 Ki-67-LI 的肿瘤对 neoadjuvant 治疗更敏感(P = 0.032 ) 。Ki-67 水平在 neoadjuvant 治疗以后减少了，但是没有统计意义被发现 P 】 0.05 ) 。我们的结果表明的结论在预告的处理的 VEGF 和 Ki-67 的表示直肠的腺癌活体检视可能对 neoadjuvant 的肿瘤反应是预兆的治疗。

Regulation Effect of Vascular Endothelial Growth Factor on Human Fetal Choroid Vascularization

Purpose:To investigate the spatial and temporal regulation effect of vascular endothelial growth factor(VEGF)on human fetal choroid vascularization.Methods:The eyeballs of 54human fetuses from the 9th week to the40th week due to accidental abortion were studied by immunohistochemically staining for the expression of VEGF and proliferation cell nuclear antigen(PCNA).Results:(1)The distribution of VEGF expression in the retinal pigment epithelium(RPE)decreased with the increase of age,the peak of which was between the 9th and 14th week,(2)PCNAimmunoreactivity was localized within choriocapillaris endothe-lium,THe expression level decreased alone with fetus age,In this period the chori-ocapillaris endothelium kept proliferation,differentiation.canalization and remodelled to form the choroid vessels.(3)Statistically significant correlations were shown between the expression of VEGF in the PRE and that of PCNAin choriocapillaris endothelium(r=0.933,P<0.01).Conclusion:VEGF expression in PRE was positively involved in modulating human fetal choroid vascularization.Eye Science2000;16:11-14.

Glutamate enhances the expression of vascular endothelial growth factor in cultured SD rat astrocytes

Objective To study the effect of glutamate on the expression of vascular endothelial growth factor (VEGF) mRNA and protein in cultured rat astrocytes. Methods Cultured rat astrocytes were randomly divided into 6 groups:control group (C),glutamate group (G),QA group (Q),DCG-IV group (D),L-AP4 group (L) and glutamate+MCPG group (G+M). Cells were cultured under nomoxic condition (95% air,5% CO2). RT-PCR and ELISA methods were used to detect the expression of VEGF mRNA and protein in cultured astrocytes,respectively. G+M group was preincubated with 1mM MCPG for 30 min prior to the stimulation with glutamate. There were 7 time points at 0,4,8,12,16,24 and 48 h in each group except G+M group. Results The expression of VEGF mRNA and protein did not differ significantly among D group,L group and C group. Different from that in C group,the expression of VEGF mRNA and protein could be enhanced both in a dose-dependent and time-dependent manner in G group and Q group. Meanwhile,the enhanced expression of VEGF mRNA and protein in G group was completely suppressed by MCPG after 24 h. Conclusion Glutamate can increase the expression of VEGF mRNA and protein in cultured astrocytes,which may be due to the activation of group I metabotropic glutamate receptors in astrocytes.

STUDY ON THE CLINICAL-PATHOLOGICAL SIGNIFICANCE OF MICROVESSEL DENSITY AND VASCULAR ENDOTHILIAL GROWTHFACTOR EXPRESSION IN PRIMARY LIVER CANCER

Objective: To evaluate the clinical-pathological significance of intratumoral microvessel density (MVD) and Vascular Endothelial Growth Factor (VEGF) expression in primary liver cancer (PLC). Methods: A retrospective study from 63 postoperative patients all with small PLC (diameter ≤5 cm) was done. One group of 29 patients developed recurrence or metastasis within 2 years. The other group of 34 patients had no evidence of recurrence or metastasis within 2 years. Three sections were taken from each patient. One for H.E. staining, the other two for VEGF and Bio-UEA-I immunohistochemical staining respectively. MVD was counted by endothelial cells, which were highlighted by Bio-UEA-I. Results: The MVD of the recurrence (or metastasis) group (49.6±29.7) were significantly greater than the other, group (22.7±28.2) (P<0.01); The VEGF positive rate of the recurrence group was 86.2% (25/29), the rate of the other group was 47.1% (16/34). the difference between the 2 groups was stafistically significant (P<0.01). The stage of the tumor, the positive rate of satellite nodules and the positive rate of the portal vein embolus were all significantly different between the 2 groups. Conclusion: Besides tumor stage, satellite nodule and portal vein embolus, the MVD and VEGF are also of prognostic significance.

EXPRESSION OF VASCULAR ENDOTHELIAL GROWTH FACTOR AND BASIC FIBROBLAST GROWTH FACTOR IN HUMAN NON-SMALL CELL LUNG CANCER AND THEIR CLINICAL SIGNIFICANCE

Objective: To explore the expression of vascular endothelial growth factor(VEGF) and basic fibroblast growth factor(bFGF) in non-small cell lung cancer(NSCLC) and theIR clinical significance. Methods: The expression of VEGF and bFGF was examined at the protein levels by immunohistochemical staining in 96 NSCLC patients, and in 36 of which at the mRNA levels by reverse transcription-PCR analysis. Results: VEGF mRNAs were expressed predominately as its secretory forms (VEGF121 and VEGF165) in NSCLC tissues. The positive ratios of VEGF121 and VEGF165 were 69.5%(25 of 36) and 41.7%(15 of 36) respectively. The positive ratio of bFGF was 52.8(19 of 36) in the same tumor specimens. The positive ratios of VEGF and bFGF at protein levels were 55.55%(20 of 36) and 58.33%(21 of 36) respectively. A significant positive correlation was observed between VEGF and bFGF expression in NSCLC tissues(P=0.002). No significant interrelationship between VEGF, bFGF expression and clinical data(age, sex, histological subtype differentiation, P-stage, metastasis and survival) was found. Conclusions: VEGF and bFGF may play an important role in angiogenesis and act in a synergistic manner in NSCLC.