CD34和VEGF在肝癌组织中的表达及与肿瘤血管生成的相关性

目的探讨CD34和血管内皮生长因子（VEGF）在肝细胞肝癌（HCC）组织中的表达及微血管密度（MVD）的临床病理意义。方法应用链霉素扰生物素蛋白-过氧化物酶法（S—P法）对50例HCC患者进行肿瘤血管生成免疫组织化学检测。对CD34阳性血管进行MVD计数．对VEGF进行半定量计数，并分析与HCC的临床病理特征的关系及意义。结果CD34在HCC组织中呈广泛、窦隙状表达，MVD值在有汇管区癌栓和肝内转移者高于无汇管区癌栓和无肝内转移者（P〈0．05），VEGF表达的阳性率在有汇管区癌栓和肝内转移者明显高于元汇管区癌栓及无肝内转移者（P〈0．05）。MVD值在VEGF阳性组和阴性组之间差异有显著性（P〈0．05）。结论HCC中MVD值和VEGF阳性表达率明显增高，由自分泌和旁分泌产生的VEGF通过促进HCC肿瘤血管生成而促进HCC的生长和转移。     

VEGF表达与鼻咽癌血管生成、瘤细胞增殖及预后的关系

目的探讨血管内皮生长因子（VEGF）表达与鼻咽癌（NPC）血管生成、肿瘤细胞增殖及预后的关系。方法选取有明确病理诊断、临床资料完整并随访5a以上的86例NPC患者活检标本,采用免疫组织化学技术检测活检标本中VEGF、微血管密度（iMVD）和增殖细胞核抗原（PCNA）的表达,并分析其与临床病理及预后的关系。结果全组VEGF阳性表达率69．9％（60／86）,与iMVD、PCNA呈显著正相关,与组织学分级、原发灶范围、淋巴结转移、临床分期及生存期亦具相关性。结论NPC组织中VEGF过表达可能参与NPC发生发展,可作为判断NPC恶性程度、侵袭能力和预后的指标。     

Galectin-1在胃癌组织中的表达及在胃癌血管生成中的作用

目的研究半乳糖凝集素1（Gal-1）在胃癌组织中的表达,并分析其与肿瘤血管生成的关系。方法采用实时荧光定量RT-PCR技术从mRNA水平检测胃癌组织及远癌切端胃组织中Gal-1的表达情况,并用免疫组织化学SABC法检测各标本中Gal-1蛋白、血管内皮生长因子（VEGF）表达及其微血管密度（MVD）。分析Gal-1、VEGF与临床病理参数及MVD之间的关系。结果胃癌组织Gal-1 mRNA及蛋白表达、VEGF表达、MVD均分别高于远癌切端胃组织（P均〈0.05）。胃癌组织Gal-1 mRNA及蛋白表达、VEGF表达和MVD与浸润深度、TNM分期及淋巴结转移相关,胃癌组织Gal-1表达与VEGF、MVD呈正相关（P〈0.05）。结论 Gal-1通过促进肿瘤微血管生成参与胃癌的生长和侵袭,可作为诊断及判断胃癌进展程度及预后的指标。     

Selective aldosterone blocker,eplerenone, attenuates hepatocellular carcinoma growth and angiogenesis in mice

Aim: The renin–angiotensin–aldosterone system (RAAS) has become known as a prerequisite for tumor angiogenesis, including hepatocellular carcinoma (HCC). Although angiotensin II is known to play an important role in tumor growth and angiogenesis, the role of aldosterone (Ald) is still obscure. The aim of our current study was to elucidate the effect of eplerenone, a clinically used selective Ald blocker (SAB), on murine HCC development especially in conjunction with angiogenesis. Methods: To create an allograft model, we injected 1 × 10⁶ of BNL‐HCC cells into the flanks of BALB/c mice. After the tumor was established, SAB was administrated at dose of 100 mg/kg per day. Results: Administration of SAB significantly suppressed HCC development along with inhibition of angiogenesis and expression of the vascular endothelial growth factor (VEGF), a potent angiogenic factor. SAB treatment resulted in a marked increase of apoptosis in the tumor, whereas tumor cell proliferation was not altered. Our in vitro study showed that SAB significantly suppressed the Ald‐induced endothelial proliferation and tubular formation through inhibition of phosphorylation of the extracellular signal‐regulated kinase 1/2. On the contrary, neither Ald nor SAB affected the proliferation of HCC cells in vitro. Conclusion: Ald plays a pivotal role in HCC development through VEGF‐mediated tumor angiogenesis, and SAB may be a potential new strategy in HCC therapy in the future.     

肝细胞癌组织微血管密度和VEGF表达及意义

目的 探讨肝细胞癌组织中微血管密度(MVD)、血管内皮生长因子(VEGF)表达特征及其与组织形态和自然病程的关系.方法 采用免疫组化法检测63例肝癌患者癌组织、癌旁组织和20例非癌肝组织中MVD及VECF表达.结果 肝细胞癌组织MVD明显高于癌旁和非癌组织(P<0.0500);低MVD者生存期明显长于高MVD者(P<0.05);癌组织VEGF表达与组织分化程度无明显相关性(P=0.1393),与MVD及预后有相关性(P分别=0.0002、0.0039).结论 VEGF参与了肝细胞癌组织血管新生;MVD及VEGF与肝细胞癌的发生发展及自然病程有关.     

Correlation between serum levels of interleukin-6 and vascular endothelial growth factor in gastric carcinoma

BACKGROUND AND AIM: Vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) are associated with the disease status of gastric carcinoma. However, their relationship remains unclear. This study aims to determine and correlate serum levels of VEGF and IL-6 in gastric carcinoma. METHODS: A total of 107 patients receiving gastrectomy entered this study. Serum levels of VEGF and IL-6 were measured by using ELISA, and were analyzed by using the Student's t-test to compare means and by Pearson correlation analysis to calculate correlation coefficients with respect to pathological characteristics including depth of tumor invasion, Laurén's classification, tumor location, Borrmann classification, and the status of lymph node metastasis. RESULTS: Serum VEGF levels were significantly higher in patients with mixed type carcinoma (387.5 +/- 176.9 vs 255.3 +/- 154.1 pg/mL, P = 0.047) or lymph node metastasis (339.1 +/- 205.1 vs 223.2 +/- 197.4 pg/mL, P = 0.007). Serum IL-6 levels were significantly higher in patients with Borrmann type IV carcinoma, compared with Borrmann type II and III carcinoma. In general, no correlation was noted between serum VEGF levels and IL-6 levels (r = 0.142, P = 0.145), but significant correlation was found in patients with early gastric carcinoma (r = 0.627, P = 0.004) or mixed type carcinoma (r = 0.804, P = 0.016). CONCLUSIONS: This study supports the correlation between serum VEGF and IL-6 levels in distinct subsets of gastric carcinoma patients, and indicates that IL-6 may play a role for the angiogenesis of gastric carcinoma via modulation of VEGF.     

Angiogenesis and the ET-1/ETA Receptor System: Immunohistochemical Expression Analysis in Bone Metastases from Patients with Different Primary Tumors

Angiogenesis is necessary for the growth of primary tumors and the formation of metastases. It is well known that vascular endothelial growth factor (VEGF) and its receptors play a major role in this process. To date, the formation of bone metastases has been poorly understood. Tumor cells must interact with the microenvironment of the bone and new blood vessels must spread. The ET/ET(A) (endothelin) receptor system seems to play an important role in this process. Specimens from metastatic bone lesions and non-malignant bone tissue were analyzed by histological and immunohistochemical staining. Sections were stained with antibodies against CD31, Flt-1, KDR, endothelin-1 (ET-1) and endothelin receptor A (ET(A)). Our studies show that there is an increased microvessel density (MVD) in metastatic bone lesions from different primary tumors in contrast to normal bone tissue. In nearly all tumor formations of the bone, ET-1 and its receptor ET(A) was found by immunohistochemistry. We also performed immunohistochemical staining for the VEGF-receptors Flt-1 and KDR. In conclusion, there is an increased vessel density in metastatic bone lesions in contrast to normal bone tissue. The ET/ET(A) system can be detected in nearly all bone specimens and is upregulated in metastatic bone lesions in contrast to healthy bone tissue.     

癌胚抗原相关细胞黏附分子1和血管内皮生长因子在HBV相关性肝癌血管生成中的作用

目的 研究癌胚抗原相关细胞黏附分子1 (CEACAMl)和血管内皮生长因子(VEGF)在HBV相关性肝癌组织中的表达与HBV相关性肝癌血管生成的关系.方法 采用免疫组织化学SP法检测81例HBV相关性肝癌组织中CEACAM1、VEGF的表达,光镜下计数CD105标记的微血管密度(MVD).结果 81例HBV相关性肝癌组...     

TFF2在胃癌、癌旁及正常胃黏膜组织中的表达及其与血管生成的关系

目的:探讨三叶因子2(TFF2)、血管内皮生长因子(VEGF)和微血管密度(MVD)在胃癌发生、发展、浸润和转移中的作用.方法:选取广西医科大学第一附属医院2008-01/2009-06接受胃大部切除术的胃癌标本50例,采用SP免疫组织化学方法检测30例正常胃黏膜组织、50例癌旁组织和50例胃癌组织中TFF2、VEGF...     

EB病毒感染与血管生成在胃癌组织芯片中的关系

目的:探讨EB病毒(Epstein-Barr virus,EBV)感染相关胃癌的构成比,其淋巴结转移癌的感染状况、临床病理特征及与血管生成的关系.方法:用原位杂交法检测胃癌组织中EBV编码的小RNA(EBERs),分析EB病毒相关胃癌的病理形态、患者年龄、性别、淋巴结转移状况等临床特征;用免疫组织化学EnVision法检测血管生成(即血管内皮生长因子(vascular endothelial growth factor,VEGF)蛋白的表达水平,分析EBV和血管生成在胃癌的表达与患者淋巴结转移状态、Lauren's分型等的关系及其相互关系.结果:486例胃癌患者中检测出感染EB病毒者(n=18,3.7%).该病毒位于肿瘤细胞核内;14例EB病毒相关胃癌患者中(77.8%)伴淋巴结转移癌,其中所有癌细胞均表达EBERs;与非EB病毒感染胃癌相比,EB病毒相关胃癌分化程度低(P<0.05),而临床TNM分期无明显差别(P>0.05);血管生成在胃癌组织中的表达率(28.2%,137/486);血管生成与患者淋巴结转移状态,TNM分期相关(P<0.05);同时,血管生成与EBV感染胃癌二者之间呈正相关(r=0.08...     

Increased expression of angiogenin in gastric carcinoma in correlation with tumor angiogenesis and proliferation

AIM: To investigate the implication of angiogenin (ANG) in the neovascularizaton and growth of human gastric carcinoma (HGC). METHODS: ANG mRNA expression in HGC specimens obtained by surgical resection from patients with HGC were examined by RT-PCR. ANG, Ki-67, VEGF protein expression and microvessel density (MVD) in HGC specimens were detected by immunohistochemistry. RESULTS: RT-PCR showed significantly higher ANG mRNA expression (0.482±0.094) in HGC tissues than in the surrounding nontumorous tissues (0.276±0.019, P=0.03). MVD within tumorous tissues increased significantly with ANG mRNA expression (r=0.380,P=0.001) and ANG protein expression (P<0.01). The ANG expression levels of cancer tissues were positively correlated with VEGF (P<0.01) and the proliferation index of cancer cells (P<0.01). CONCLUSION: ANG is one of the neovascularization factors of HGC. ANG may work in coordination with VEGF, and promote the proliferation of HGC cells.     

Multiple angiogenesis stimulators in a single malignancy: implications for anti-angiogenic tumour therapy

Anti-angiogenesis is likely to develop into a novel therapeutic approach for patients with solid malignancies. Most current clinical trials evaluate anti-angiogenic drugs aimed primarily against single angiogenesis stimulators. Here, we show that a single solid malignancy, i.e., a human embryonal rhabdomyosarcoma, produces in vivo at least three biologically active angiogenesis stimulators (vascular endothelial growth factor, basic fibroblast growth factor and interleukin-8). This suggests that tumour angiogenesis results from the activity of multiple, rather than a single angiogenesis stimulator(s). We, furthermore, show that a combination of anti-angiogenic drugs is more effective in inhibiting tumour-induced endothelial cell growth than a single agent. Our results imply that clinical anti-angiogenic strategies for the treatment of solid malignancies may be most effective when multiple rather than single anti-angiogenic drugs are used. This revised version was published online in June 2006 with corrections to the Cover Date.     

血管内皮生长因子受体与肝细胞癌血管生成关系的研究进展

新生血管是肿瘤生长和转移的基础.肝细胞肝癌是典型的多血管肿瘤,其发生、发展、转移、侵袭都和血管生成密切相关.血管的生成主要依靠血管生长因子和血管生长抑制因子的调控,其中研究最多也是最重要的是血管内皮生长因子(VEGF)及其受体(VEGFR).VEGFR在机体内作用不同,参与肝癌血管生长的主要是VEGFR-1(flt-1)和VEGFR-2(flk-1).针对VEGFR的抗肿瘤血管治疗在实验室取得了不错的疗效,部分已经进入了临床试验.     

畸胎瘤细胞源性生长因子和血管内皮生长因子在食管鳞癌中的表达及临床意义

目的 探讨食管鳞癌(ESCC)中畸胎瘤细胞源性生长因子(PCDGF)、血管内皮生长因子(VEGF)的表达与肿瘤临床病理参数之间的关系,明确PCDGF和VEGF在血管生成中的作用.方法 以免疫组化方法检测郑州大学第一附属医院2005年7月至2006年5 月收治的50例食管鳞癌患者手术切除标本PCDGF与VEGF的表达,并以CD105抗体标记肿瘤组织血管内皮细胞,计算肿瘤间质微血管密度(MVD).结果 食管鳞癌中PCDGF、VEGF的表达较正常食管上皮明显增加(P＜0.01);PCDGF和VEGF与肿瘤的浸润深度、TNM分期和淋巴结转移呈正相关(P均＜0.05);PCDGF、VEGF的表达与MVD值呈显著正相关(P＜0.01);PCDGF的表达与VEGF的表达呈正相关(P＜0.05).结论 PCDGF标记癌组织的敏感性较高,有望成为一种新的食管鳞癌肿瘤标志物.食管鳞癌中PCDGF、VEGF的表达与血管生成关系密切,可能通过促进肿瘤新生血管生成参与肿瘤的生长、浸润和转移.     

慢性肝炎及肝炎相关肿瘤与血浆血管内皮生长因子表达的研究

前瞻性评估慢性乙型肝炎及乙肝相关肿瘤与血浆血管内皮细胞生长因子(VEGF)表达的关系。采用酶 联免疫夹心法(ELISA)测定血浆VEGF,分别对20例健康成人、20例慢性乙型肝炎及40例HCC患者测量血浆VEGF 水平。结果显示:乙肝患者VEGF水平显著高于健康成人;乙肝患者VEGF水平低于HBsAg阴性肿瘤;HBsAg阳性 肿瘤患者VEGF水平显著高于HBsAg阴性患者。VEGF表达水平与肝病严重程度成正相关,HBsAg阳性肝细胞癌血 浆VEGF表达显著增加。     

Expression pattern of angiogenic factors and prognosis after hepatic resection in hepatocellular carcinoma: importance of angiopoietin-2 and hypoxia-induced factor-1 alpha.

BACKGROUND: Hepatocellular carcinoma (HCC) is a hypervascular tumor and angiogenesis plays an important role in its progression. Angiogenesis is regulated by a balance between pro and antiangiogenic molecules. The aim of this study was to investigate the expressions of angiogenic factors and elucidate their roles in angiogenesis in HCC. METHODS: We investigated immunohistochemical expression of vascular endothelial growth factor (VEGF), angiopoietins (Ang-1 and Ang-2), hypoxia-induced factor-1alpha (HIF-1alpha) and thrombospondin-1 (TSP-1) in 60 specimens of surgically resected HCC. We investigated the relationship between their expressions and clinicopathological factors or prognosis. RESULTS: Ang-2 staining had a significant correlation with the grade of differentiation of HCC cells (P=0.0082). VEGF and Ang-2 expression correlated positively with microvessel density (MVD) (P=0.0061 and 0.0374, respectively). MVD of well-differentiated HCC were significantly lower than those of moderately and poorly differentiated HCC. The disease-free survival time of patients with high Ang-2 and/or HIF-1alpha expression was significantly shorter than that of the low expression group (P=0.0278 and 0.0374, respectively). CONCLUSION: Our study showed that the expression of VEGF and Ang-2 correlated with MVD. Strong Ang-2 expression and/or high nuclear expression of HIF-1alpha is a significant predictive factor for recurrence after curative resection in HCC patients.     

Involvement of cyclooxygenase-2 and vascular endothelial growth factor in vascularization and lymph node metastasis of colorectal cancers with submucosal invasion

BACKGROUND AND AIMS: Although patients with early colorectal cancer invading the submucosa (CRC-sm) may be treated with endoscopic mucosal resection alone, they generally undergo additional surgery because of the risk of lymph node metastasis. The aims of the present study were to examine the roles of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) in tumor vascularization and to investigate whether COX-2 and VEGF expression and tumor vascularity are useful markers for predicting lymph node metastasis in CRC-sm. METHODS: Twenty-seven resected specimens of CRC-sm with lymph node dissection were examined, and expression of COX-2 and VEGF was evaluated immunohistochemically and scored. Microvessel density (MVD) in CRC-sm tissues was estimated using a Macscope system after CD34 immunostaining. The relationships among clinicopathological parameters, COX-2 and VEGF expression, and MVD in CRC-sm tissues were then analyzed. RESULTS: Scores for COX-2, VEGF and MVD were all significantly higher in patients with CRC-sm with lymphatic invasion or lymph node metastasis. COX-2 score (P < 0.0001) and VEGF score (P = 0.035) were significantly correlated with MVD in CRC-sm tissues. In addition, COX-2 score was significantly correlated with VEGF score in the CRC-sm specimens examined. CONCLUSIONS: Both COX-2 and VEGF are involved in tumor vascularization in CRC-sm. COX-2 expression, VEGF expression, and MVD are possible markers for predicting lymph node metastasis in patients with CRC-sm, and use of COX-2 expression may be clinically practical.