Vascular endothelial growth factor (VEGF) expression in plasmacytoma

Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis. Although the role and importance of angiogenic factors such as VEGF have been established in various solid tumors, this has not been widely evaluated in hemopoietic neoplasias. In this trial, VEGF was studied in plasmacytoma and VEGF expression was compared with histopathologic grade. Forty-seven samples have taken from cases with plasmacytoma (Pm) (33 bones and 14 soft tissue plasmacytomas) were used as study material. Pm was the initial presentation in all cases, and bone marrow (BM) involvement was detected in 19 cases with systemic evaluation. Twenty-seven of the cases were male (age range was between 19 and 81 years). Histopathologically 27 cases had mature and 20 cases had immature morphology. Immunohistochemical analysis was used to detect VEGF expression and this was scored according to the percentage of the VEGF stained cells. VEGF expression was detected in 32 cases and in eight cases this expression was strong. In 11 cases expression was moderate and 13 cases showed mild expression. When we compared VEGF expression with pathologic grade, 17 of 20 immature samples showed VEGF expression while 15 of 27 mature samples showed VEGF expression. There was a statistically significant association between immature morphology and VEGF expression (p < 0.0264). Additionally all the samples, except one, with strong VEGF expression showed immature morphology. In conclusion two thirds of the cases with Pm showed VEGF expression and this was associated with immature morphology. Increased expression of VEGF was seen in plasmacytomas, and additional studies are needed to determine whether this translates to increased microvasculature or increased risk of progression to myeloma.     

Vascular endothelial growth factor (VEGF) expression in operable gallbladder carcinomas

AIM: To investigate the angiogenic and prognostic role of vascular endothelial growth factor (VEGF) in operable gallbladder carcinomas. METHODS: Sixty patients with early gallbladder carcinomas, treated with surgery alone, were investigated immunohistochemically for the expression of VEGF, thymidine phosphorylase (TP) and new blood vessel formation. The results were correlated with clinico-pathological features and prognosis. RESULTS: An increased VEGF secretion in gallbladder carcinomas was significantly associated with increased angiogenesis but not with patients survival, although high angiogenesis did relate with poor prognosis. TP was also associated with angiogenesis, but only the combined VEGF/TP expression was associated with unfavourable survival. Histological grade was another independent factor of prognosis. CONCLUSION: Both VEGF and TP expression are associated with high rate of angiogenesis, a factor directly associated with prognosis. The combined expression of these angiogenic factors confer a particularly poor post-operative outcome, speculature.     

Vascular endothelial growth factor-C expression in human prostatic carcinoma and its relationship to lymph node metastasis.

Lymph node dissemination is a major prognostic factor in human cancer. However, the molecular mechanisms underlying lymph node metastasis are poorly understood. Recently, vascular endothelial growth factor-C (VEGF-C) was identified as a ligand for VEGF receptor-3 (VEGFR-3/Flt-4) and the expression of VEGFR-3 was found to be highly restricted to the lymphatic endothelial cells. In this report, we investigated the expression of VEGF-C and VEGFR-3 in human prostatic carcinoma tissue by using in situ hybridization and immunohistochemical staining respectively. Expression of VEGF-C mRNA in prostatic carcinoma was significantly higher in lymph node-positive group than in lymph node-negative group. In addition, the number of VEGFR-3-positive vessels was increased in stroma surrounding VEGF-C-positive prostatic carcinoma cells. These results suggest that the expression of VEGF-C in prostatic carcinoma cells is implicated in the lymph node metastasis.     

Vascular endothelial growth factor and its relationship to inflammatory mediators.

Inflammation occurs in response to host injury or infection, as the result of an autoimmune disease, or in response to the development of a tumor. Although the immune system may be helpful in fighting the tumor, it may also fuel the tumorigenic process. In fact, recent data suggest a strong link between chronic inflammation, angiogenesis, and the development of cancer. For example, inflammation and scarring caused by recurring infections with Mycobacterium tuberculosis may be a cause for cancers of the lung. Inflammatory breast cancer exhibits increased angiogenesis and lymphangiogenesis and has a higher metastatic potential than noninflammatory breast cancer. Nonsteroidal anti-inflammatory drugs have been proposed as preventives for the development of colon carcinoma and ovarian cancer. Inhibition of nuclear factor-kappaB contributes to the proposed mechanism of action. Inflammatory cytokines, including interleukin-6, serve as autocrine and paracrine growth factors for several cancers, and high levels of these cytokines may correlate with a poor prognosis and increased production of angiogenic factors. The state of the art of our understanding of this critical interaction is reviewed.     

VEGF和 bFGF在浅表膀胱移行细胞癌中的表达及意义

背景与目的：血管内皮生长因子（vascular endothelial growth factor,VEGF)和碱性成纤维细胞生长因子（basic fibroblast growth factior,bFGF)都能促进血管内皮细胞分裂和诱导血管形成,是肿瘤的生长,浸润,和转移过程中非常重要的物质,但它们在单发性和多发性浅表膀胱移行细胞癌中表达的差异则未见报道,本研究主要是探讨VEGF和bFGF在浅表膀胱移行细胞癌中的表达及意义。方法：采用免疫组化法对60例浅表膀胱移行细胞癌组织及10例正常膀胱组织进行VEGF和bFGF的检测,观察单发性和多发性浅表膀胱移行细胞癌组织中VEGF和bFGF表达的关系。结果：多发性浅表膀胱移行细胞癌的VEGF阳性率为55.6%,bFGF阳性率为50.0%,以及VEGF和bFGF共同表达阳性率为50.0%。均明显高于单发者的水平,而高水平表达的多发性肿瘤患者的术后复发率61.1%也明显高于单发组的复发率（单发组的复发率16.7%)。结论：VEGF和bFGF表达水平的高低与浅表膀胱移行细胞癌的生物学行为有关。     

Vascular endothelial growth factor (VEGF) inhibition by small molecules

Angiogenesis is essential for primary tumours to grow and metastasise, and is driven by the production of positive angiogenic factors. The Vascular Endothelial Growth Factor (VEGF) family is central to the process of angiogenesis and comprises 5 molecules designated A, B, C, D and E. VEGF is overexpressed in several solid malignancies. The actions of VEGF are mediated through receptors possessing tyrosine kinase activity: VEGFR-1 (Flt-1), VEGFR-2 (Kdr/Flk-1) and VEGFR-3 (Flt-4). Anti-VEGF strategies include the use of antibodies to VEGF or its receptors, the use of ribozymes to decrease receptor expression, and the use of inhibitors of tyrosine kinase to reduce receptor activation and downstream signalling. The focus of this review is small molecule inhibitors of VEGF receptors which target their intrinsic tyrosine kinase activity. The clinical development of the following agents is discussed: SU5416, SU11248, SU6668, PTK/ZK, ZD6474.     

Vascular endothelial growth factor (VEGF) mRNA expression in human tumor models of different histologies

Background: Vascular endothelial growth factor (VEGF) is a polypeptidewith specific effects on endothelial cell growth and blood vesselpermeability. Recent studies demonstrated a key role for VEGFin tumor neovascularization, which is a prerequisite for tumorproliferation and metastasis Patients and methods: We studied the expression of VEGF mRNAin a panel of 65 different human tumor xeno-grafts of varioushistologies using Northern and slot blot analyses. Analysisof vessel density was performed morphologically and after immunohistochemicalstaining of endothelial cells Results: High expression levels were observed in 22/65 tumors.In melanoma, colorectal, gastric, breast and lung cancers onlysingle tumors showed strong expression signals, whereas 7/10renal cell carcinoma (RCC) xenografts demonstrated high levelsof VEGF mRNA. Vessel density analysis revealed a clear correlationof VEGF mRNA expression with vascularization in RCC (p - 0.0048).Patient survival time was compared for tumors showing high versuslow expression values. The overall 5-year survival rate wassignificantly lower for patients with high expression of VEGFmRNA (p - 0.0306) Conclusions: These data support the hypothesis that tumor cellsof various histologies secrete VEGF, which acts as a paracrinefactor to induce endothelial cell proliferation and vessel formationand mediates tumor progression VEGF, VPF, angiogenesis, vascularization, renal cell carcinoma, human tumor xenografts     

胰腺癌组织中VEGF的表达与血管计数的关系

目的　研究血管内皮生长因子（ＶＥＧＦ）在胰腺癌组织血管形成中的作用。方法采用免疫组织化学 ＡＢＣ法研究了３３的胰腺癌标本中 ＶＥＧＦ的表达及分布,并研究了ＶＥＧＦ的表达强度与肿瘤血管计数的关系。结果（１）２２例（６６．７％）强表达ＶＥＧＦ, ８例（２４．２％）表达呈中等强度,３例（９．１％）呈弱阳性。ＶＥＧＦ在癌细胞呈胞浆内染色,肿瘤间质血管内皮细胞及瘤周正常组织中也可见 ＶＥＧＦ着色。（２）ＶＥＧＦ中等强度以上染色的病例中７例（２３．３％）血管计数不足 ２０个,弱阳性的标本中 １例计数达 １５个。（３）ＶＥＧＦ表达强度与肿瘤血管计数存在显著相关性（Ｐ＜０．０５）。结论ＶＥＧＦ在胰腺病组织血管形成过程中起重要作用,可以作为肿瘤血管抑制治疗的靶因子。     

VEGF上调survivin和bcl-2表达及抑制乳腺癌细胞凋亡的机制探讨

目的研究血管内皮细胞生长因子(VEGF)对乳腺癌细胞株MCF-7的凋亡及凋亡相关基因survivin和bcl-2表达的影响,探讨VEGF自分泌作用抑制肿瘤细胞凋亡的机制.方法构建VEGF165真核表达质粒,采用脂质体转染VEGF165 cDNA MCF-7细胞, 通过RT-PCR及ELISA方法鉴定转染克隆MCF-7/hVEGF165细胞中VEGF mRNA及蛋白的表达,Western blot 方法比较MCF-7/hVEGF165及MCF-7、MCF-7/pcDNA3细胞中survivin、bcl-2蛋白表达,流式细胞仪分析细胞凋亡和细胞周期.结果 MCF-7/hVEGF165细胞VEGF mRNA表达量增加,细胞培养上清中VEGF蛋白浓度为(354.50±31.93)ng/L,高于MCF-7细胞的(178.54±16.52)ng/L和MCF-7/pcDNA细胞的(190.75±13.32)ng/L(P<0.01).与MCF-7、MCF-7/pcDNA3组相比较,MCF-7/hVEGF165细胞凋亡百分数显著下降(P<0.05),分别为(2.47±0.51)% (MCF-7/hVEGF165),(7.74±1.56)%(MCF-7/pcDNA3)和(7.35±0.33)%(MCF-7);survivin和bcl-2蛋白表达增高了近3倍,但各组细胞周期变化不明显(P>0.05).结论 VEGF诱导凋亡抑制基因suvivin和bcl-2高表达,可能在自分泌VEGF抑制MCF-7凋亡中发挥重要作用.     

Vascular endothelial growth factor (VEGF) in leptomeningeal metastasis: diagnostic and prognostic value

This study examined the diagnostic and prognostic value of vascular endothelial growth factor (VEGF) levels in the cerebrospinal fluid (CSF) of 39 patients with leptomeningeal metastasis (LM). Vascular endothelial growth factor levels at diagnosis were significantly higher in patients with LM (median 359 pg ml(-1)) than in patients with other neurological diseases (median <25 pg ml(-1)). The specificity of VEGF levels above 250 pg ml(-1) for LM was high (98.3%), while the sensitivity was low (51.4%; 73% for VEGF values above 100 pg ml(-1)). In 49% of the LM patients, particularly with lymphoma or medulloblastoma, VEGF levels were below 250 pg ml(-1) and thus in the range of VEGF levels in other neurological diseases. Vascular endothelial growth factor levels correlated significantly with CSF lactate and albumin. Vascular endothelial growth factor levels mirrored the clinical course with a marked reduction in response to therapy and an increase at relapse in some patients who had serial CSF samples available. Multivariate Cox regression analysis showed VEGF below 100 pg ml(-1) (relative risk (RR)=4.24, P=0.0002) and age below 60 years (RR=2.5, P=0.004) to be associated with longer survival in LM. In conclusion, CSF VEGF levels in LM vary considerably. High VEGF levels have a very high specificity for LM and may help to establish the diagnosis. The role of VEGF as a predictor of outcome should be substantiated in prospective studies.     

Vascular endothelial growth factor (VEGF) upregulates BCL-2 and inhibits apoptosis in human and murine mammary adenocarcinoma cells.

Tumour progression is regulated by the balance of proliferation and apoptosis in the tumour cell population. To date, the role of vascular endothelial growth factor (VEGF) in tumour growth has been attributed to the induction of angiogenesis. VEGF has been shown to be a survival factor for endothelial cells, preventing apoptosis by inducing Bcl-2 expression. In both murine (4T1) and human (MDA-MB-231) metastatic mammary carcinoma cell lines, we found that VEGF upregulated Bcl-2 expression and anti-VEGF antibodies reduced Bcl-2 expression. These alterations in Bcl-2 expression were reflected by the levels of tumour cell apoptosis. VEGF resulted in reduced tumour cell apoptosis, whereas its inhibition with anti-VEGF neutralizing antibodies induced apoptosis directly in tumour cells. Therefore, in addition to its role in angiogenesis and vessel permeability, VEGF acts as a survival factor for tumour cells, inducing Bcl-2 expression and inhibiting tumour cell apoptosis.     

血管内皮生长因子在脑星形细胞瘤中的表达及其意义

目的　探讨血管内皮生长因子 (VEGF)在脑星形细胞瘤中的表达及其与肿瘤生长、预后和血管生成的关系。方法　应用免疫组化方法检测 82例脑星形细胞瘤瘤组织中VEGF表达、MVD ,并分析VEGF表达与血管生成、病理分级、临床预后等临床病理的关系。结果　VEGF表达与MVD呈正相关 (r=0 .6 3,P <0 .0 1)。星形细胞瘤病理级别越高 ,VEGF表达越强 (P <0 .0 5 ,0 .0 1)。瘤周水肿越重 ,VEGF表达也越强 (P <0 .0 5 ,0 .0 1)。VEGF表达与星形细胞瘤的大小、发生部位及男女性别无明显的相关关系 (P >0 .0 5 )。结论　星形细胞瘤的VEGF表达与其血管生成、预后及病理分级密切相关 ,可作为判断预后的独立指标。     

VEGF硫代反义寡核苷酸抑制U937细胞VEGF的表达

Objective： To study the effect of VEGF antisense oligodeoxynucleotide （VEGF ASODN） on VEGF expression in acute monocyte leukemic cell line U937 in vitro. Methods： U937 cells were incubated with VEGF ASODN （final concentration as follows： 10, 20 and 30 μmol/L respectively） or scrambled sequence, compared with negative control. The expression of VEGF mRNA was measured by semi-quantitative RT-PCR, VEGF protein was measured by Western blot. Results： VEGF ASODN obviously inhibited expression of VEGF mRNA in U937 cell, compared with scrambled sequence and negative control （P〈0.05）. And the inhibition effect was most remarkable after 24 h, which is related with the dose of VEGF ASODN （P〈0.05）. Scrambled sequence groups had no significant difference compared with negative control groups （P〉0.05）. VEGF ASODN obviously inhibited expression of VEGF protein, compared with scrambled sequence and negative control （P〈0.05）. Conclusion： The expressions of VEGF at mRNA and protein levels in leukemic cell line U937 are down-regulated after being treated with VEGF ASODN.     

Vascular endothelial growth factor (VEGF) expression is a prognostic factor for radiotherapy outcome in advanced carcinoma of the cervix

The aim of the study was to evaluate VEGF expression in tumour biopsies as a prognostic factor for radiotherapy outcome in advanced carcinoma of the cervix. A retrospective study was carried out on 100 patients. Pre-treatment tumour VEGF expression was examined immunohistochemically in formalin-fixed, paraffin-embedded biopsies using a widely available commercial antibody. A semi-quantitative analysis was made using a scoring system of 0, 1, 2, and 3, for increasing intensity of staining. High VEGF expression was associated with a poor prognosis. A univariate log rank analysis found a significant relationship with overall survival (P = 0.0008) and metastasis-free survival (P = 0.0062), but not local control (P = 0.23). There was no correlation between VEGF expression and disease stage, tumour differentiation, patient age, or tumour radiosensitivity (SF2). In a Cox multivariate analysis of survival VEGF expression was the most significant independent prognostic factor (P = 0.001). After allowing for VEGF only SF2 was a significant prognostic factor (P = 0.003). In conclusion, immunohistochemical analysis of VEGF expression is a highly significant and independent prognostic indicator of overall and metastasis-free survival for patients treated with radiotherapy for advanced carcinoma of the cervix. It is also a rapid and easy method that could be used in the clinical setting, to identify patients at high risk of failure with conventional radiotherapy who may benefit from novel approaches or chemoradiotherapy.     

Vascular endothelial growth factor (VEGF) expression is not associated with prognosis in patients with radically resected ampullary carcinoma.

Vascular endothelial growth factor (VEGF) is known to be a potentangiogenic mitogen that plays an important role in tumor angiogenesis[1]. The correlation between the expression of VEGF and eithermetastasis or a poor prognosis has been reported for severalcancers [2]. Kurahara and colleagues demonstrated that VEGFexpression in patients with pancreatic head cancer is significantlyassociated with lymphatic metastasis and prognosis [3].     

Progestins suppress estrogen-induced expression of vascular endothelial growth factor (VEGF) subtypes in uterine endometrial cancer cells.

Vascular endothelial growth factor (VEGF) contributes to the early advancement of uterine endometrial cancers that conserve hormone dependency via angiogenic activity. This process prompted us to study sex steroidal suppression of VEGF expression in Ishikawa cells (a line of well-differentiated uterine endometrial cancer cells). Estrogen transiently induced VEGF subtype (VEGF165 and VEGF121) secretion from Ishikawa cells. Progestins (progesterone, medroxyprogesterone acetate (MPA) and 17 alpha-hydroxyprogesterone) suppressed the estrogen-induced events. In conclusion, progestins could suppress VEGF-related angiogenic potential, which contributes to tumor growth in the early stage of uterine endometrial cancers that conserve estrogen dependency.     

Expression of vascular endothelial growth factor (VEGF) and its two receptors in diffusely infiltrating astrocytomas and relationship to proliferative activity of tumor cells

We studied the relationships among vascular endothelial growth factor (VEGF), its receptors (Flt1 and Flk1), and MIB-1. Their expression in 47 diffusely infiltrating astrocytomas obtained at surgery or autopsy was investigated by the ABC method and analyzed quantitatively. The positive rate of VEGF in tumor cells was higher than that in endothelial cells, and Flk1 was lower in tumor cells (P<0.01, 0.01), whereas Flt1 in both tumor cells and endothelial cells was found at similar levels (P>0.05). In tumor cells, VEGF became high with increased histological grades (P<0.01), whereas both Flt1 and Flk1 were higher in grade 4 than in grades 2 and 3 (P<0.01, 0.05). VEGF, Flt1, and Flk1 in endothelial cells were also highly expressed in grade 4 (P<0.01). The distribution of MIB-1-positive nuclei in grade 4 was similar to VEGF, and the percent of positivity from grade 2 to grade 4 also increased (P<0.01). There was a linear positive correlation between VEGF and both Flt1 and Flk1 in both tumor cells and endothelial cells (P<0.01). So was the percent of positivity with VEGF, Flt1, and Flk1 in tumor cells and endothelial cells (P<0.01). The experiment suggests that VEGF may act as a growth factor for both endothelial cells and tumor cells. VEGF, Flt1, and Flk1 can be considered as indicators of the malignancy potential of diffusely infiltrating astrocytomas. The expression of VEGF and the two receptors may be affected by the proliferative activity of tumor cells.