肾癌组织中血管内皮生长因子表达的意义

目的 探讨肾癌组织中血管内皮生长因子（VEGF）的表达及与临床病理的关系。方法 应用免疫组织化学方法,对6例肾癌组织中的VEGF进行检测。结果 肾癌组织中VEGF阳性表达率为73．9％,阳性着色于细胞质和细胞膜,VEGF表达与肿瘤大小、细胞类型和病理分级均无关（P＞0．05）,Ⅲ＋Ⅳ期强阳性表达率明显高于Ⅰ Ⅱ期（P＜0．05）,VEGF阳性表达者5年生存率明显低于阴性表达者。结论 VEGF表达与肾癌生物行为有重要影响,其可能成为预测肾癌转移和预后的指标。     

人脑膜瘤血管内皮生长因子表达及生物学意义

[目的]研究血管内皮生长因子(VEGF)在人脑膜瘤中的表达及其生物学意义.[方法]采用免疫组织化学方法检测51例脑膜瘤(WHO分级良性38例,非典型11例,恶性2例)VEGF蛋白的表达水平和微血管密度(MVD).[结果]良性脑膜瘤VEGF阳性表达率86.8%(33/38),不典型、恶性脑膜瘤VEGF阳性表达率为84.6%(11/13)(P＞0.05).而3例正常脑膜组织未见VEGF表达(P＜0.05).良性、非典型及恶性脑膜瘤的MVD分别为131.08±115.93和145.12±99.21(P＞O.05),VEGF表达阴性的脑膜瘤其MVD为88.25±59.86,VEGF表达呈 、 、 的MVD为102.25±149.55,108.12±54.43,172.36±118.58,两者表达成正相关(r=O.45,P＜0.05).VEGF表达与脑膜瘤的侵袭性、脑浸润性无关.[结论]VEGF在脑膜瘤的血管形成中起重要作用,可能参与脑膜瘤的形成,但与脑膜瘤的良性向非典型转变、脑浸润性、侵袭性等生物学特性无关.     

SNP and Haplotype Analysis of Vascular Endothelial Growth Factor (VEGF) Gene in Lung Cancer Patients of Kashmir

Vascular endothelial growth factor (VEGF) is a major mediator of angiogenesis involving tumor growth and metastasis. In this large case-control study, we investigated whether functional polymorphisms (+405C>G, +936C>T) in the VEGF gene are associated with the risk of lung cancer. The study investigates the association between variants of VEGF gene and lung cancer. We performed single nucleotide polymorphism (SNP), haplotype and linkage disequilibrium studies on 100 patients and 128 healthy controls with 2 SNPs in the VEGF gene. The results were analyzed using logistic regression models, adjusted for age and sex. No Significant association was detected between individual SNPs and lung cancer using all the models of inheritance (codominant, dominant, recessive, over dominant and additive) for finding an association between genotypes and the cancer risk. The P values obtained for two markers were non-significant (P>0.05). Haplotype analysis produced additional support for the non-association of individual haplotypes/ all haplotypes with the cancer risk (Global association P=0.56). Our findings suggest the non-involvement of genetic variants (+405C>G, +936C>T) of the VEGF gene in the etiology of lung cancer.     

Vascular Endothelial Growth Factor (VEGF) Gene Polymorphisms and Breast Cancer Risk in a Chinese Population

Vascular endothelial growth factor (VEGF) is a potent regulator of angiogenesis and thereby involved in thedevelopment and progression of solid tumours. Associations between three VEGF gene polymorphisms (-634G/C, +936 C/T, and +1612 G/A) and breast cancer risk have been extensively studied, but the currently availableresults are inconclusive. Our aim was to investigate associations between three VEGF gene polymorphisms andbreast cancer risk in Chinese Han patients. We performed a hospital-based case-control study including 680female incident breast cancer patients and 680 female age-matched healthy control subjects. Polymerase chainreaction restriction fragment length polymorphism (PCR-RFLP) analysis was performed to detect the threeVEGF gene polymorphisms. We observed that women carriers of +936 TT genotypes [odds ratio (OR) =0.46,95% confidence interval (CI) = 0.28, 0.76; P=0.002] or 936 T-allele (OR=0.81, 95% CI= 0.68, 0.98; P=0.03) hada protective effect concerning the disease. Our study suggested that the +1612G/A polymorphism was unlikelyto be associated with breast cancer risk. The -634CC genotype was significantly associated with high tumoraggressiveness [large tumor size (OR=2.63, 95% CI=1.15, 6.02; P=0.02) and high histologic grade (OR=1.47,95% CI= 1.06, 2.03; P=0.02)]. The genotypes were not related with other tumor characteristics such as regionalor distant metastasis, stage at diagnosis, or estrogen or progesterone receptor status. Our study revealed thatthe VEGF -634 G/C and +936 C/T gene polymorphisms may be associated with breast cancer in Chinese Hanpatients.     

鼻咽癌患者血清血管内皮生长因子水平的临床意义

目的　分析血管内皮生长因子 (VEGF)在鼻咽癌 (NPC )患者血循环的含量及其临床意义。方法　采用酶联免疫吸附试验 (ELISA )测定 14 0例NPC患者 (治疗前组 63例 ,完全缓解组 41例 ,复发组 3 6例 )和 40例健康人血清VEGF水平。结果　NPC患者治疗前、完全缓解和复发组血清VEGF水平分别为 ( 2 96.5± 183 .6)ng/L、( 2 78.7± 169.6)ng/L和 ( 3 69.3± 3 15 .6)ng/L ,均显著高于健康对照组的 ( 180 .9± 14 7.7)ng/L(分别为P <0 .0 1、P <0 .0 5、P <0 .0 1) ;血清VEGF水平随着NPC进展有上升趋势 ,尤其是发生远处转移者 ;高水平VEGF的患者更易发生肿瘤复发转移。结论　NPC患者血清VEGF水平上升 ,与肿瘤的侵袭有密切关系     

血管内皮生长因子(VEGF)和血清癌胚抗原(CEA)在直肠癌中的表达及其临床意义

目的 探讨血管内皮生长因子(VEGF)和血清癌胚抗原(CEA)在直肠癌中的表达意义.方法 选择60例直肠癌患者为研究对象,并选取同期体检健康者60例作为对照组.使用免疫化学发光法和免疫组化法分别测定血清CEA水平和VEGF蛋白表达水平,分析其表达水平及临床关系.结果 ①研究组血清中CEA检测值明显高于对照组,P＜0.05;②在不同直肠癌TNM分期中,肿瘤组织中CEA阳性率除T1、T2组之间无统计学差异(P =0.153)外,其余各组比较均有统计学差异(P＜0.05);在N分期不同阶段,肿瘤组织CEA阳性率各组间比较差异有统计学意义;在不同M分期中,CEA阳性率分别为43.8％ (M0)、88.7％ (M1),组间比较差异有统计学意义;在不同病理分期中CEA阳性率:Ⅰ期～Ⅱ期与Ⅲ期～Ⅳ期比较差异有统计学意义(P＜0.05),Ⅰ期与Ⅱ期、Ⅲ期与Ⅳ期组间比较差异没有统计学意义(P＞0.05);③肿瘤组织中VEGF表达与肿瘤浸润程度(T分期)有关(P=0.01),与淋巴转移程度(N分期)相关(P-0.03),与临床病理分期有相关性(P=0.009).结论 血管内皮生长因子(VEGF)和血清癌胚抗原(CEA)均与直肠癌的发病密切相关,并与临床TNM分期表现出明显相关性,对直肠癌的临床诊断、治疗和预后有重要意义.     

血管内皮生长因子在急性白血病患者中表达的研究

目的：探讨血管内皮生长因子在急性白血病患者的表达及其与各临床病理特征的关系。方法：采用免疫组织化学的方法检测40例自愿急性白血病患者治疗前后骨髓细胞VEGF的表达。结果：VEGF在急性白血病患者中表达明显高于对照组，治疗后缓解组VEGF表达水平明显下降。有髓外转移组VEGF表达明显高于无髓外转移组。结论：急性白血病患者中存在VEGF高表达，可能与急性白血病的发病、转移及疾病的预后有关。     

胶质瘤中VEGF表达与微血管密度的关系及其临床意义

背景与目的:VEGF在肿瘤血管生成中起重要作用。本研究旨在探讨VEGF在人脑胶质瘤中的表达与微血管密度的关系及其临床意义。方法:采用免疫组化二步法检测36例人脑胶质瘤组织和8例非肿瘤对照脑组织中VEGF蛋白表达,采用CD34抗体标记测定微血管密度(miarovessel density,MVD)和并测算水肿指数(edema index,EI)。结果:(1)VEGF蛋白主要分布在高分级胶质瘤组织瘤细胞的胞浆内,低分级胶质瘤呈低水平表达,非肿瘤对照脑组织中VEGF蛋白均表达为阴性。VEGF在人脑胶质瘤中的总表达率77.8%(28/36)。(2)高分级(Ⅲ、Ⅳ级)胶质瘤MVD(68.88±19.05个/HP)也相对于低分级(Ⅰ、Ⅱ级)胶质瘤MVD(37.82±12.37个/HP)高(t=5.116,P<0.01)。(3)高分级(Ⅲ、Ⅳ级)胶质瘤水肿程度相对低分级(Ⅰ、Ⅱ级)胶质瘤程度较重。高分级胶质瘤EI与低分级胶质瘤EI之间有显著性差异(t=3.852,P<0.01)。(4)VEGF表达阳性者MVD(53.35±15.71个/HP)显著高于VEGF表达阴性者(15.76±5.38个/HP)(P<0.01),VEGF表达阳性者EI(3.45±1.63)显著高于VEGF表达阴性者(1.35±0.41)(P<0.05)。结论:VEGF的表达水平对判断人脑胶质瘤的临床病理级别有重要的价值。VEGF表达和MVD、EI检测结果可作为人脑胶质瘤生物学行为的判断指标。     

Overexpression of Vascular Endothelial Growth Factor 165 (VEGF165) Protects Cardiomyocytes Against Doxorubicin-Induced Apoptosis

Abstract

Doxorubicin (Dox) has been employed in cancer chemotherapy for a few decades. However its clinical application became restricted because of dose-dependent cardiomyopathy. Recent studies suggest that Dox-induced cardiomyocyte apoptosis is a primary cause of cardiac damage. Vascular endothelial growth factor (VEGF) is a major factor for endothelial cell survival and angiogenesis. We have previously shown that VEGF₁₆₅ significantly attenuates oxidative stress-induced cardiomyocytes apoptosis. We hypothesized that VEGF₁₆₅ will protect the cardiomyocytes from Dox-induced apoptosis. to evaluate our hypothesis, we transfected cardiomyocytes H9c2 with adenovirus expressing VEGF₁₆₅ 24 hours before the cells were challenged with Dox at a concentration of 2 μm. Cardiomyocyte apoptosis was evaluated by Annexin V-FITC staining and by Western blot detection of cleaved caspase-3. The hypothesis was confirmed, and the protective mechanisms involve the inhibition of death receptor-mediated apoptosis and up-regulation of the prosurvival Akt/NFB/Bcl-2 signaling pathway.     

Correlations of oral tongue cancer invasion with matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) expression

BACKGROUND AND OBJECTIVES: In oral tongue cancer, the degree of tumor invasion has a significant effect on the prognosis. We hypothesized that the destruction of extracellular matrix and neovascularization are related to tumor infiltration mechanism. By studying the tissues of early stage oral tongue cancer patients, we are intending to clarify the invasion-related factors. MATERIALS AND METHODS: To demonstrate the invasion process in early T-stage oral tongue cancer, the expressions of extracellular matrix destruction-related molecules (MMP-2, MMP-9) and neovascularization-related molecule (VEGF) were observed by immunohistochemical study. Also, staining of CD31 was done for quantification of neovascularization. We analyzed relationship between expression of each substances and tumor invasion depth, tumor free survival rates, and cervical lymph node metastasis rate. RESULTS: The expression rates of MMP-2, MMP-9, VEGF in 38 early oral cancer patients were 52.6%, 78.9%, and 52.6%, respectively. Significant correlation was found between the VEGF expression and microvessel density showed by CD31 immunohistochemical staining (P < 0.001). VEGF expressions were significantly related with tumor invasion depth (P = 0.002). The tumor-free survival rate of those patients with VEGF-positive tumors was significantly poorer than in those with VEGF-negative tumors (P = 0.019). CONCLUSIONS: These results indicate that VEGF is a useful marker for predicting the tumor invasion in patients with early tongue cancer.     

125I偶联VEGF反义寡核苷酸对人膀胱癌VEGF的抑制作用研究

目的观察125I偶联VEGF反义寡核苷酸(125I-ASODN)对膀胱癌细胞VEGF表达的抑制情况.方法采用免疫组化法观察125I-ASODN对膀胱癌细胞VEGF表达的影响,并观察条件培养液对内皮细胞生长的抑制作用.结果免疫组化结果显示对照组VEGF阳性细胞数为平均89.1/100个细胞,125I-Na处理组为90.3/100个细胞,ASODN组为10.3/100个细胞,125I-ASODN组为4.3/100个细胞,125I-ASODN组和ASODN组与对照组及125I-Na组比较,差异有显著性意义(P<0.05);对照组、125I-Na处理组、ASODN组、125I-ASODN组D值分别为0.398±0.031,0.387±0.010,0.298±0.013和0.148±0.011,125I-ASODN组和ASODN组D值与对照组及125I-Na组比较,差异有非常显著性(P<0.01).结论 125I-ASODN 能够明显抑制膀胱癌细胞的VEGF表达,可作为临床抗血管生成治疗膀胱癌的一种有效方法.     

血管内皮生长因子在肿瘤中的表达及其临床意义

肿瘤的生长、浸润和转移依赖于肿瘤血管生成 ,血管内皮生长因子 (VEGF)是最重要的一种血管生成刺激因子。VEGF特异性作用于血管内皮细胞 ,通过促进内皮细胞增殖、增加血管通透性 ,以诱导肿瘤血管生成 ,在肿瘤的发生发展中起关键作用。因而VEGF在肿瘤的恶性程度和预后判断以及治疗方面有重要的临床应用价值。     

人胃癌VEGF和NOS的表达及其相关性

目的：研究VEGF、iNOS和eNOS在人胃癌的表达及其相关性；研究N0和VEGF的相互作用及在促肿瘤生长中的作用机制。方法：应用免疫组化方法检测34例胃癌标本VEGF、iNOS和eNOS的表达及分布。结果：1)34例胃癌组织中，表达iNOS的为73．5％，表达eNOS的为82．4％，表达VEGF的占91．2％。2)VEGF与iNOS的表达具有明显相关性(入0．005)，VEGF与eNOS的表达无明显相关性(Pb0．05)。结论：VEGF与iNOS的表达具有明显相关性，iNOS在VEGF的生成和发挥过程中起重要作用。     

Targeting Vascular Endothelial Growth Factor (VEGF) for Anti-tumor Therapy, by Anti-VEGF Neutralizing Monoclonal Antibodies or by VEGF Receptor Tyrosine-kinase Inhibitors

Vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) is an important mediator of tumor-induced angiogenesis and represents a potential target for innovative anticancer therapy. In several animal models, neutralizing anti-VEGF/VPF antibodies have shown encouraging inhibitory effects on solid tumor growth, ascites formation and metastatic dissemination. Targeting the VEGF signaling pathway by means of VEGF receptor tyrosine-kinase inhibitors has shown similar efficacy in animal tumor models. Several of these anti-VEGF therapies are currently being tested in clinical trials in cancer patients. The profiles and effects of the neutralizing anti-VEGF/VPF antibodies and the VEGF receptor tyrosine-kinase inhibitors in animal models are reviewed and of the risks and benefits of VEGF blockade by one or the other treatments are discussed.     

Prognostic Value of Vascular Endothelial Growth Factor Expression in Resected Gastric Cancer

Background and Aims: Vascular endothelial growth factor (VEGF) is a potential prognostic biomarker forpatients with resected gastric cancer. However, its role remains controversial. The objective of this study was toconduct a systematic review and meta-analysis of published literature. Methods: Relevant literature was identifiedusing Medline and survival data from published studies were collected following a methodological assessment.Quality assessment of eligible studies and meta-analysis of hazard ratio (HR) were performed to review thecorrelation of VEGF overexpression with survival and recurrence in patients with gastric cancer. Results: Ourmeta-analysis included 44 published studies with 4,794 resected patients. VEGF subtype for the prediction ofoverall survival (OS) included tissue VEGF (HR=2.13, 95% CI 1.71–2.65), circulating VEGF (HR=4.22, 95% CI2.47–7.18), tissue VEGF-C (HR=2.21, 95% CI 1.58–3.09), tissue VEGF-D (HR=1.73, 95% CI 1.25–2.40). Subgroupanalysis showed that HRs of tissue VEGF for OS were, 1.78 (95% CI 0.90-3.51) and 2.31 (95% CI 1.82-2.93) innon-Asians and Asians, respectively. The meta-analysis was also conducted for disease free survival (DFS) anddisease specific survival (DSS). Conclusion: Positive expression of tissue VEGF, circulating VEGF, VEGF-C andVEGF-D were all associated with poor prognosis in resected gastric cancer. However, VEGF demonstrated nosignificant prognostic value for non-Asian populations. Circulating VEGF may be better than tissue VEGF inpredicting prognosis.     

A Phase II Safety and Efficacy Study of the Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitor Pazopanib in Patients With Metastatic Urothelial Cancer

BackgroundVascular endothelial growth factor (VEGF) is produced by bladder cancer cell lines in vitro and expressed in human bladder tumor tissues. Pazopanib is a vascular endothelial receptor tyrosine kinase inhibitor with anti-angiogenesis and anti-tumor activity in several preclinical models. A 2-stage phase II study was conducted to assess the activity and toxicity profile of pazopanib in patients with metastatic, urothelial carcinoma.MethodsPatients with one prior systemic therapy for metastatic urothelial carcinoma were eligible. Patients received pazopanib at a dose of 800 mg orally for a 4-week cycle.ResultsNineteen patients were enrolled. No grade 4 or 5 events were experienced. Nine patients experienced 11 grade 3 adverse events. Most common toxicities were anemia, thrombocytopenia, leucopenia, and fatigue. For stage I, none of the first 16 evaluable patients were deemed a success (complete response or partial response) by the Response Evaluation Criteria In Solid Tumors criteria during the first four 4-week cycles of treatment. Median progression-free survival was 1.9 months. This met the futility stopping rule of interim analysis, and therefore the trial was recommended to be permanently closed.ConclusionsPazopanib did not show significant activity in patients with urothelial carcinoma. The role of anti-VEGF therapies in urothelial carcinoma may need further evaluation in rational combination strategies.     

口腔鳞癌中VEGF表达和肿瘤相关巨噬细胞在血管生成中相互作用的初步研究

目的:探讨口腔鳞癌中血管内皮生长因子(vascular endothelial growth factor VEGF)和肿瘤相关巨噬细胞(tumor-associated macrophages TAMs)在肿瘤血管生成中的关系。方法:采用免疫组化染色,光镜进行高倍视野下巨噬细胞、微血管计数、图像分析,以观察VEGF表达的强度,免疫组化双染观察巨噬细胞内VEGF的表达。结果:在口腔鳞癌中VEGF的表达与微血管计数(P<0.05,γ=0.412)及肿瘤相关巨噬细胞计数(P<0.05,γ=0.376)有关,免疫组化双染显示,TAMs内有VEGF的表达。结论:口腔鳞癌中与TAMs和VEGF表达有关,二者相互作用促进肿瘤的血管生成,参与肿瘤生长和转移。     

食管癌原发灶及转移淋巴结血管内皮生长因子和微血管形成的测定

目的 :探讨食管鳞状细胞癌原发灶和淋巴结转移灶血管内皮生长因子 (VEGF)表达及微血管形成的规律。方法 :用免疫组化方法测定 35例食管癌标本原发灶和转移灶VEGF表达水平及微血管密度(MVD)。结果 :淋巴结转移灶VEGF表达水平高于原发灶 (P <0 .0 1) ;淋巴结转移灶、原发灶及阴性淋巴结MVD分别为 11 33± 4 .4 4、13 85± 5 57、18 6 1± 6 6 7,淋巴结转移灶与后两者相比差异均有显著性 (P <0 .0 1)。结论 :转移灶VEGF表达水平高于原发灶 ,淋巴结内可能存在抗肿瘤血管生成因素。