血管内皮生长因子及微血管密度在肝癌中的表达

目的 :探讨血管内皮生长因子 (VEGF)在肝癌微血管形成中的作用以及与原发性肝癌生物学行为的关系。方法 :选择 32例原发性肝癌手术标本 ,采用免疫组织化学方法测定血管内皮生长因子及Ⅷ因子的蛋白表达。结果 :血管内皮生长因子在原发性肝癌中的阳性表达率为 6 5 .6 3% ;原发性肝癌中肿瘤微血管密度 (MVD)为 30 .96± 12 .32 ,其中血管内皮生长因子表达阴性者MVD为 19.12± 7.34 ,血管内皮生长因子表达阳性者MVD为 42 .36±15 .5 4,二者相比有显著差异 (P <0 .0 1)。结论 :血管内皮生长因子能促进肿瘤中微血管形成 ,血管形成在原发性肝癌的生长和转移中起到重要的作用。     

大肠癌组织血内皮生长因子表达与血管生成和细胞增殖关系的研究

目的：研究血管内皮生长因子（VEGF）在大肠癌组织中的表达及其与血管生成和细胞增殖的关系。方法：应用免疫组织化学方法检测98例大肠癌组织中VEGF表达及微血管密度（MVD）、PCNA标记指数（PCNA LI）,并分析VEGF与MVD、PCNA LI的相关性。结果：98例大肠癌中,VEGF表达阳性36例（３６．７％）;VEGF表达阳性的肿瘤其ＭＶＤ和ＰＣＮＡ ＬＩ显著高于VEGF阴性（Ｐ＜０．０５）。VEGF表达与ＭＶＤ、ＰＤＮＡ LI显示正相关（P＜0．05）。有转移组（有包淋结转移移和远处转移VEGF表达明显高于无转移,VEGF表达随肿瘤分期的升高而增高。结论：VEGF在大肠癌血管生成和细胞增殖中起重要作用。     

乳腺癌血流动力学的超声表现与血管内皮生长因子及微血管密度的诊断标准

目的 研究血流动力学的超声表现与血管内皮生长因子及微血管密度诊断乳腺癌的价值.方法 选择乳腺癌患者98例,采用彩色多普勒超声检查进行血流动力学分级,采用免疫组化SP法检测血管内皮生长因子及微血管密度.观察超声表现与血管内皮生长因子及微血管密度的关系.结果 超声血流动力学与血管内皮生长因子之间差异具有统计学意义(x2=6.535,P--0.043),血流动力学分级越大,血管内皮生长因子阳性患者越多.超声血流动力学与微血管密度之间差异具有统计学意义(x2 =9.632,P=0.021),血流动力学分级为0级、Ⅰ级时微血管密度≤20患者均明显多于＞ 20患者(P＜0.05),Ⅱ级和Ⅲ级时微血管密度≤20患者均明显少于＞20患者(P＜0.05);与单一指标检测相比,联合诊断的特异性、敏感性和准确性均明显升高(P＜0.05),假阴性率和假阳性率明显降低(P＜0.05).结论 联合检测血流动力学、血管内皮生长因子及微血管密度在乳腺癌的诊断中具有重要价值,能为乳腺癌患者的诊断、治疗和预后提供有效的临床信息,值得应用推广.     

Targeting Angiogenesis in Cancer Therapy: Moving Beyond Vascular Endothelial Growth Factor

Angiogenesis, or the formation of new capillary blood vessels, occurs primarily during human development and reproduction; however, aberrant regulation of angiogenesis is also a fundamental process found in several pathologic conditions, including cancer. As a process required for invasion and metastasis, tumor angiogenesis constitutes an important point of control of cancer progression. Although not yet completely understood, the complex process of tumor angiogenesis involves highly regulated orchestration of multiple signaling pathways. The proangiogenic signaling molecule vascular endothelial growth factor (VEGF) and its cognate receptor (VEGF receptor 2 [VEGFR-2]) play a central role in angiogenesis and often are highly expressed in human cancers, and initial clinical efforts to develop antiangiogenic treatments focused largely on inhibiting VEGF/VEGFR signaling. Such approaches, however, often lead to transient responses and further disease progression because angiogenesis is regulated by multiple pathways that are able to compensate for each other when single pathways are inhibited. The platelet-derived growth factor (PDGF) and PDGF receptor (PDGFR) and fibroblast growth factor (FGF) and FGF receptor (FGFR) pathways, for example, provide potential escape mechanisms from anti-VEGF/VEGFR therapy that could facilitate resumption of tumor growth. Accordingly, more recent treatments have focused on inhibiting multiple signaling pathways simultaneously. This comprehensive review discusses the limitations of inhibiting VEGF signaling alone as an antiangiogenic strategy, the importance of other angiogenic pathways including PDGF/PDGFR and FGF/FGFR, and the novel current and emerging agents that target multiple angiogenic pathways for the treatment of advanced solid tumors.

Implications for Practice:

Significant advances in cancer treatment have been achieved with the development of antiangiogenic agents, the majority of which have focused on inhibition of the vascular endothelial growth factor (VEGF) pathway. VEGF targeting alone, however, has not proven to be as efficacious as originally hoped, and it is increasingly clear that there are many interconnected and compensatory pathways that can overcome VEGF-targeted inhibition of angiogenesis. Maximizing the potential of antiangiogenic therapy is likely to require a broader therapeutic approach using a new generation of multitargeted antiangiogenic agents.     

子宫颈癌组织中VEGF与TGF-β1间关系的探讨

目的:探讨血管内皮生长因子(VEGF)及转化生长因子(TGF-β1)在宫颈癌组织中的表达及其与宫颈癌临床病理特征的关系.方法:采用免疫组化链霉菌抗生物素蛋白-过氧化物酶连接染色法检测30例宫颈癌Ⅰ期、Ⅱ期患者癌组织中VEGF、TGF-β1的表达,并进行统计学分析.结果:VEGF、TGF-β1在宫颈鳞癌Ⅰ期、Ⅱ期均为高表达.VEGF在宫颈癌Ⅰ期、Ⅱ期、有淋巴转移者的表达率分别为78.3%、71.4%、100%.TGF-β1表达率分别为91.3%、42.9%、75.0%,其表达与年龄、肿瘤体积、浸润深度有关.结论:VEGF可促进肿瘤细胞的增生和转移;TGF-β1与肿瘤的发生、发展有关,可能使肿瘤细胞逃脱免疫监视.     

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。     

一氧化氮合酶和血管内皮生长因子在大肠癌组织中的表达及其与血管生成的关系

目的 研究诱导型与内皮型一氧化氮合酶(iNOS、eNOS)和血管内皮生长因子(VEGF)在大肠癌组织中的表达及其与血管生成的关系。方法 应用免疫组化方法检测72例大肠癌手术切除标本中iNOS、eNOS、vEGF的表达，并与正常大肠黏膜、腺瘤组织相比较。结果 iNOS和eNOS在大肠癌组织中的平均表达阳性率分别为70．83％、36．11％，与正常黏膜、腺瘤比较有显著性差异（P＜0．05)。大肠癌组织中iNOS表达与VEGF表达有一致性(P＜0．05)。结论 iNOS在由VEGF介导的大肠癌血管形成中发挥一定的作用。     

血管内皮细胞生长因子在非小细胞肺癌中的表达

目的探讨血管内皮细胞生长因子(VEGF)、肿瘤微血管密度(MVD)2项指标与非小细胞肺癌各临床病理因素之间的关系以及两者之间的联系。方法采用免疫组织化学SABC法检测经病理检查确诊的68例非小细胞肺癌、13例癌旁和13例正常肺上皮组织VEGF、FVⅢ因子相关抗原的表达,对FVⅢ因子相关抗原标记的血管计数MVD。结果肺癌组织VEGF阳性表达率和MVD值明显高于正常肺上皮组织和癌旁组织;肿瘤直径≥5.0cm者MVD值明显高于直径<5.0cm者;腺癌MVD值明显高于鳞癌;有远处器官转移的肺癌MVD值明显高于无远处器官转移者;Ⅳ期肺癌MVD值明显高于Ⅰ期和Ⅱ期者,Ⅲ期MVD明显高于Ⅰ期,MVD值随TNM分期增加有逐渐增高的趋势;VEGF表达阳性的肺癌MVD值明显高于表达阴性者,并且随着VEGF表达程度的加强,MVD值增加。结论血管生成与肺癌的生长、浸润、转移及疾病进展密切相关;肺癌组织VEGF阳性表达率明显增加,是肺癌血管形成和维持的重要因子之一;MVD可作为判断非小细胞肺癌生物学行为,预测其发生发展的1项指标。     

VEGF及其受体KDR在垂体腺瘤中的表达与肿瘤血管形成的关系

 目的　探讨血管内皮生长因子(VEGF) 及其受体( KDR) 的表达与垂体腺瘤血管生成的关系。方法　应用免疫组织化学S2P 法检测58 例人垂体腺瘤中的V E GF 及KD R 的表达,并对血管进行染色、计数。结果　其中54 例有VEGF 的表达(占93. 1 %) ,阳性表达主要位于肿瘤细胞胞膜及胞浆; KD R 在47 例中有阳性表达(占81. 0 %) ,阳性表达位于肿瘤血管内皮细胞、肿瘤细胞胞膜及胞浆。VEGF 和KD R 表达与垂体腺瘤的侵袭性密切相关;V E GF 和KD R 高表达组微血管密度明显高于低表达组( P <0. 01) 。结论　VEGF 以旁分泌、自分泌形式协同KDR 促进垂体腺瘤血管的生成,并与垂体腺瘤的侵袭密切相关。     

微血管定量和血管内皮生长因子表达在肠型胃癌中的意义

为研究血管形成和血管形成因子表达在肠型胃癌和弥漫型胃癌中的作用，应用抗因子Ⅷ相关抗原抗体、抗ＶＥＧＦ抗体及抗ｂＦＧＦ抗体的免疫组化ＬＳＡＢ法，分别对６３例肠型胃癌和４５例弥漫型胃癌中的微血管数量（ＭＶＣ）、ＶＥＧＦ和ｂＦＧＦ表达进行研究。ＭＶＣ和ＶＥＧＦ及ｂＦＧＦ表达在肠型胃癌明显高于弥漫型胃癌（Ｐ分别＜０．０５，０．００１和０．０１），同样，ＭＶＣ和ＶＥＧＦ表达在肝转移患者明显高于腹膜转移者（Ｐ分别＝０．００１和＜０．０１）；在肠型胃癌中，ＭＶＣ与ＶＥＧＦ表达明显相关（Ｐ＝０．０２），ＭＶＣ和ＶＥＧＦ表达随ＴＮＭ分期增加而增加，而与弥漫型胃癌无关。两型胃癌中的ｂＦＧＦ表达均与ＭＶＣ无关。本研究结果表明肠型胃癌的转移形式为血管依赖性，ＶＥＧＦ可能是诱导肠型胃癌血管形成的一个重要因子。     

血管内皮生长因子在食管癌中的表达和临床意义

目的探讨食管癌血管内皮生长因子（ＶＥＧＦ）、血管生成与食管癌临床病理特点的关系。方法采用免疫组织化学技术,检测５０例食管癌组织ＶＥＧＦ蛋白表达和微血管密度（ＭＶＤ）。分析ＶＥＧＦ和ＭＶＤ的关系及其与食管癌组织学分型、浸润度、生长方式、淋巴结转移和预后的关系。结果ＶＥＧＦ阳性者ＭＶＤ值显著高于阴性者,ＶＥＧＦ及ＭＶＤ与食管癌浸润深度、淋巴结转移密切相关,与组织学分型、生长方式也有明显相关性。结论ＶＥ     

长效醋酸甲羟孕酮对子宫内膜癌组织中血管内皮生长因子的影响

目的 探讨长效醋酸甲羟孕酮对子宫内膜癌组织中血管内皮生长因子的影响.方法 选择原发性子宫内膜癌患者80例作为观察组,同时选取80例正常增生期子宫内膜组织做对照.比较观察组治疗前后与对照组VEGF的表达情况.结果 治疗前,观察组中VEGF阳性表达较对照组高,差异具有统计学意义(χ2=46.673,P<0.05);治疗后,2组VEGF阳性表达率比较,差异具有统计学意义(χ2=6.972,P<0.05).治疗后,观察组VEGF阳性表达较治疗前降低,差异具有统计学意义(χ2=14.171,P<0.05).治疗前和治疗后,子宫内膜癌患者病变组织中VEGF表达在不同年龄、组织分级、病理分期、病理类型、肌层浸润深度有不同,差异具有统计学意义(P均<0.05).结论 VEGF可通过促进血管形成参与到子宫内膜癌的发生发展过程,采用长效醋酸甲羟孕酮治疗子宫内膜癌可降低患者血管内皮生长因子的表达,从而抑制肿瘤的发生发展.     

VEGF及其受体KDR在宫颈癌的联合表达与局部肿瘤血管生成的关系

目的:探讨血管内皮生长因子及其受体KDR在早期宫颈癌的表达及其对宫颈癌肿瘤血管生成的作用。方法:采用免疫组织化学SP法检测18例宫颈上皮内瘤样病变(cervicalintraepithelialneoplasm,CIN)、75例早期宫颈癌(invasivecarcinomaofcervix,ICC)和15例正常宫颈上皮(normalcervicalepithelium,NCE)中VEGF和KDR的表达情况,并检测其中微血管密度(CD34标记)。结果:在ICC中,VEGF和KDR主要表达于癌细胞膜和(或)细胞浆;而CD34主要表达于癌巢间质血管内皮细胞。从NCE到CIN再到ICC,VEGF与KDR的阳性表达率以及MVD均显著升高(P<0.01)。在ICC中,VEGF、KDR阳性表达者其MVD分别显著高于VEGF、KDR阴性表达者(P<0.05)。VEGF在ICC的表达与KDR显著正相关(r=0.56,P<0.01),并且两者均与MVD显著正相关(前者r=0.60,P<0.01;后者r=0.33,P<0.01)。VEGF与KDR均阳性表达者,其微血管密度显著高于两者均阴性表达者(P<0.01)。结论:VEGF及其受体KDR表达在宫颈癌肿瘤血管生成中起上调作用,两者均过度表达,肿瘤血管生成显著增加。检测VEGF及其受体KDR的联合表达对进一步了解宫颈癌血管生成情况以及寻找抗肿瘤血管生成治疗新靶点有一定价值。     

Genetic Effects of Vascular Endothelial Growth Factor A (VEGF-A) and Its Association with Disease Progression in Breast Cancer Population of Saudi Arabia

Aim: Previous studies have shown that vascular endothelial growth factor (VEGFA) gene variants were associated with breast cancer risk. The goal of the current study was to evaluate the genetic effects of the vascular endothelial growth factor (VEGF) on the risk of breast cancer and its association with disease progression. Methodology: This case control study was conducted on 110 Breast cancer cases and 110 gender matched healthy controls. Vascular endothelial growth factor A (VEGF-A) 1 (-460T>C) genotyping was performed using Amplification refractory mutation system PCR method. The vascular endothelial growth factor A (VEGF-A) (-460T>C) genotypes were collated with different clinicopathological features of breast cancer patients. Results: A significant difference was observed between the genotype distribution of VEGF-A (-460T>C) among breast cancer cases and gender matched healthy controls (p=0.006). The frequencies of all three genotypes CC,CT,TT reported in the breast cancer patients and sex matched healthy controls were  4.54%, 46.36% ,49.20%  and 7.27%, 64.54%, 28.18% respectively. The increased susceptibility to breast cancer disease was found to be associated with VEGF (-460T>C) CC vs TT variant in codominant inheritance model OR 2.78 (0.83-9.26) RR 1.68(1.01 to 2.81) P=0.04. A significant association was reported with VEGF (-460T>C) (CC+CT vs. TT) variant in recessive inheritance model, (OR=2.45 (95% CI= (1.40-4.29), P=0.003. Our findings indicated that VEGF (-460T>C) TT genotype is associated with an increased susceptibility to breast cancer disease. Our result indicates a potential dominant effect of VEGF (-460T>C) TT genotype on susceptibility to the breast cancer disease. Conclusion: VEGF (-460T>C) TT genotype significantly increased the risk of breast cancer. VEGF-A (-460T>C) genetic ariability was significantly associated with distant metastasis of the disease. It may be a useful as predisposing genetic marker for breast cancer .Further studies with larger sample sizes are necessary to confirm our findings.     

Expression of Vascular Endothelial Growth Factor and E-Cadherin in Human Ovarian Cancer: Association with Ascites Fluid Accumulation and Peritoneal Dissemination in Mouse Ascites Model

Ascites formation and peritoneal dissemination are critical problems in patients with advanced ovarian cancer. Vascular endothelial growth factor (VEGF), also known as angiogenic growth factor, is a potent mediator of peritoneal fluid accumulation and angiogenesis of tumors. E-Cadherin is an adhesion molecule that is important for cell-to-cell interaction. To elucidate the molecular mechanism of ascites formation and peritoneal dissemination of ovarian cancer, we examined the expression of VEGF and E-cadherin in different ovarian cancer cell lines and utilized nude mice to compare the biological characteristics of ovarian cancer cells. Three human ovarian cancer cell lines (AMOC-2, HNOA and HTBOA) were used in this study. Expression of genes was analyzed by northern blotting and RT-PCR methods. AMOC-2 expressed E-cadherin, but not VEGF. HNOA expressed VEGF without E-cadherin expression. HTBOA expressed both VEGF and E-cadherin. Each human ovarian cancer model revealed a specific feature. The AMOC-2 mouse had a single large peritoneal tumor without ascites or remarkable peritoneal dissemination. HTBOA and HNOA mice had bloody ascites and marked peritoneal dissemination. Introduction of VEGF antisense into HTBOA cells could inhibit the ascites formation. It is suggested that VEGF is important for the ascites formation via the increased vascular permeability effect. The deregulation of E-cadherin expression might be involved in the peritoneal dissemination. These molecules are important for the formation of specific features of advanced ovarian cancer. Ovarian cancer cell lines that had different gene expression patterns produced nude mouse human ovarian cancer models with different characteristics.     

The Determination of VEGF and MVD,among Patients with Primary Breast Cancer

The purpose of the study was to ascertain the value of assessment of vascular endothelial growth factor (VEGF) levels and microvessel density, and to search for correlations between them, in women with breast cancer. The assessment considered factors such as the stage of clinical disease advancement-according to International Union Against Cancer, the grade of histological malignancy, status of axillary lymph nodes and the size of the primary tumour. The concentration of VEGF was assessed in the plasma of 103 women with breast cancer, using an immunoenzymatic method (Quantikine test of R&D Systems). Assessment of microvessel density was performed using histopathological immunoperoxidase methods, using an anti-von Willebrand factor antibody (DAKO A/S). A statistically significant relationship was found between rising VEGF levels and microvessel density in women with breast cancer, when compared to values from a control group. A correlation was found between VEGF concentration and microvessel density (MVD) values. Statistically significant differences were found between VEGF levels of patients in stages I, II and III of clinical disease advancement. For MVD, differences were found only between stages I and III. A statistical relationship was also found between VEGF and MVD and tumour size. Similar results were found between VEGF concentrations in women with metastases to the axillary lymph nodes and cytokine levels in women with no metastases. The results of the study suggest that the degree of tumour vascularization and the concentration of VEGF may represent valuable indicators for the assessment of the angiogenic process in women with breast cancer.     

儿童恶性胶质瘤VEGF表达与血管生成及细胞增殖的关系

研究血管内皮细胞生长因子在儿童恶性胶质瘤的表达及其与血管生成,细胞增殖的关系。方法免疫组化方法检测３３例儿童恶性胶质瘤组织中ＶＥＧＦ表达与微血管数、ＰＣＮＡ标记指数。结果３３例儿童恶性胶质瘤ＶＥＧＦ表达阳性２３例;