MiR-126、血管内皮生长因子的表达与微血管密度在上皮性卵巢癌组织中的变化

目的 探讨miR-126、血管内皮生长因子(VEGF)的表达与微血管密度(MVD)在上皮性卵巢癌组织中的变化及意义.方法 采用qRT-PCR检测21例正常卵巢组织、23例良性卵巢肿瘤组织及45例上皮性卵巢癌组织中miR-126表达水平,采用免疫组化法检测VEGF蛋白表达及MVD.结果 MiR-126在上皮性卵巢癌组织中的表达明显低于正常卵巢组织、良性卵巢肿瘤组织(P<0.05);VEGF阳性率和MVD在上皮性卵巢癌组织中明显高于正常卵巢组织、良性卵巢肿瘤组织(P<0.05).上皮性卵巢癌组织中miR-126、VEGF及MVD与FIGO分期、淋巴结转移有关(P<0.05).结论 MiR-126、VEGF可能与上皮性卵巢癌的发生、发展、肿瘤异常血管营养及侵袭转移有关.     

COX-2、VEGF及MMP-9蛋白在上皮性卵巢癌组织中的表达及意义

目的 探讨环氧化酶-2(COX-2)、血管内皮生长因子(VEGF)及基质金属蛋白酶-9(MMP-9)在上皮性卵巢癌组织中的表达及意义.方法 采用免疫组化S-P法检测COX-2蛋白在65例上皮性卵巢癌、18例交界性卵巢肿瘤、18例良性上皮性卵巢肿瘤及9例正常卵巢组织中的表达;采用免疫组化S-P法检测VEGF、MMP-9蛋白在65例上皮性卵巢癌组织中的表达;分析COX-2蛋白与VEGF、MMP-9蛋白的表达是否存在相关性.结果 COX-2蛋白在上皮性卵巢癌及交界性卵巢肿瘤组织中的表达显著高于良性卵巢肿瘤及正常卵巢组织(P＜0.05).COX-2蛋白的过表达与上皮性卵巢癌组织中VEGF和MMP-9蛋白的表达均呈正相关(r=0.310、0.385,P＜0.05).结论 COX-2在上皮性卵巢癌及交界性卵巢肿瘤组织中的表达明显增强;COX-2可能参与上皮性卵巢癌的肿瘤血管生成及癌细胞侵袭的过程,在上皮性卵巢癌发生发展过程中起一定作用.     

上皮性卵巢恶性肿瘤组织中环氧合酶血管内皮生长因子CD34蛋白和碱性成纤维细胞生长因子的表达及意义

目的探讨环氧合酶(COX-2)、血管内皮生长因子(VEGF)、CD34和碱性成纤维细胞生长因子(b FGF)表达与上皮性卵巢恶性肿瘤的关系。方法采用免疫组化法检测30例正常卵巢组织和78例上皮性卵巢恶性肿瘤组织中COX-2、VEGF、CD34和b FGF的表达。结果 COX-2、b FGF、VEGF、CD34在上皮性卵巢恶性肿瘤组织中呈高表达,且COX-2、b FGF、VEGF在上皮性卵巢恶性肿瘤不同病理分级和不同FIGO分期患者中的表达差异有统计学意义(P<0.05)。COX-2在上皮性卵巢恶性肿瘤组织中与VEGF和b FGF有明显相关性(P<0.05)。微血管密度(MVD)在COX-2阳性表达组织和COX-2阴性表达组织中差异有统计学意义(P<0.05);COX-2与MVD有明显相关性(P<0.05)。结论 COX-2在上皮性卵巢恶性肿瘤组织中呈过度表达,COX-2作为治疗卵巢恶性肿瘤的靶点,COX-2在上皮性卵巢恶性肿瘤组织中的表达与b FGF、VEGF、CD34和MVD密切相关。     

内皮抑素和血管内皮生长因子在卵巢癌组织中的表达及其临床意义

背景与目的:血管内皮生长因子(vascularendothelialgrowthfactor,VEGF)能够诱导血管生成,导致肿瘤的生长、侵袭及远处转移;内皮抑素(endostatin)强效抑制肿瘤血管生成,进而抑制肿瘤生长、侵袭和转移。为探讨内皮抑素和VEGF在卵巢癌组织中的表达及其与卵巢癌发生发展的关系,本研究拟从基因和蛋白水平研究二者在卵巢癌组织中的表达情况。方法:运用逆转录聚合酶链反应(RT-PCR)和免疫组织化学染色法检测内皮抑素和VEGF在正常卵巢组织、卵巢癌组织中的表达情况。结果:卵巢癌组织中内皮抑素和VEGFmRNA表达水平及蛋白阳性率均高于正常卵巢组织(P<0.05);临床Ⅲ、Ⅳ期卵巢癌组织中内皮抑素和VEGFmRNA表达水平及蛋白阳性率均高于Ⅰ、Ⅱ期(P<0.05);内皮抑素mRNA≤0.5组和mRNA>0.5组,其蛋白阳性率分别为29.4%和77.8%(P<0.05);VEGFmRNA≤0.5组和mRNA>0.5组,其蛋白阳性率分别为20.0%和72.0%(P<0.05)。结论:正常卵巢组织和卵巢癌组织中内皮抑素、VEGFmRNA和蛋白含量的变化是一致的,内皮抑素与VEGF比例失调可能是卵巢癌发生发展的重要机制之一。     

宫颈癌患者血管内皮生长因子和微血管密度表达与侵袭转移的关系

目的探讨宫颈癌患者血管内皮生长因子(VEGF)及其微血管密度(MVD)的表达与肿瘤侵袭转移的关系。方法采用免疫组织化学方法检测52例慢性宫颈炎组织及60例宫颈癌组织VEGF及MVD的表达情况。结果宫颈癌组织及慢性宫颈炎组织VEGF阳性率分别为61.7%和7.7%,差别具有统计学意义(P<0.05);宫颈癌组织MVD计数显著高于慢性宫颈炎组织(45.38±10.28 VS 5.10±1.12,P<0.05);VEGF及MVD表达与肿瘤淋巴转移、临床分期及分化程度显著相关(P<0.05),而与年龄、病理分型无相关性(P>0.05)。结论宫颈癌组织VEGF及MVD表达显著升高,且与肿瘤的侵袭性密切相关,二者高表达患者预后不良。     

血管内皮生长因子在上皮性卵巢癌中的临床病理研究

目的研究血管内皮生长因子(VEGF)在上皮性卵巢癌组织中的表达状况并分析其与临床病理参数之间的关系。方法采用免疫组化、原位杂交技术分别检测31例上皮性卵巢癌、17例卵巢上皮性良性肿瘤及5例正常卵巢组织中VEGF蛋白质及核酸表达水平。结果上皮性卵巢癌组织中VEGF和VEGF mRNA阳性表达率分别为51.6%(16/31)和48.4%(15/31),与良性肿瘤相比有显著性差异(P<0.05)。上皮性卵巢癌中VEGF阳性表达率分别与淋巴结转移及腹水量密切相关(P<0.05),而在不同组织类型、病理分级及临床分期中无明显差异(P>0.05)。恶性肿瘤患者生存状况与癌组织中VEGF阳性表达率亦无相关性(P>0.05)。结论VEGF蛋白质及其mRNA在上皮性卵巢癌中高水平表达,且其阳性率与淋巴结转移及腹水量密切相关,可作为卵巢癌侵袭性评估的指标之一,为VEGF及其受体作为卵巢癌的治疗靶点提供科学依据。     

E-cadherin、VEGF蛋白在卵巢浆液性交界性肿瘤中的表达及其生物学意义

目的:探讨卵巢浆液性交界性肿瘤(sBOT)中E-钙黏附素(E-cadherin)和血管内皮生长因子(VEGF)的表达特点及临床病理意义.方法:采用免疫组化技术检测E-cadherin和VEGF在良性卵巢浆液性肿瘤、卵巢浆液性交界性肿瘤和卵巢浆液性恶性肿瘤中的表达特点,分析与sBOT临床病理指标的相关性.结果:E-cadherin在良性卵巢、交界性卵巢和恶性卵巢组织中表达呈下降趋势(P＜0.01),而VEGF在各组表达呈明显上升趋势(P＜0.01),两者存在负相关性.E-cadherin和VEGF在sBOT和低级别卵巢恶性肿瘤中表达无明显差异(P＞0.05).VEGF高表达与sBOT病理亚型、浸润性病灶和sBOT临床分期有关(P＜0.05).E-cadherin低表达与sBOT病理亚型、浸润性病灶有关(P＜0.05).结论:E-cadherin低表达或缺失和VEGF高表达与卵巢浆液性肿瘤的良恶性有关,联合检测可为卵巢交界性肿瘤预后判断提供依据.VEGF表达与sBOT的预后、转移关系密切.     

卵巢上皮性癌中APE／Ref-1的表达及与VEGF和MVD的关系

目的 探讨无嘌呤无嘧啶核酸内切酶/氧化还原因子-1(APE/Ref-1)在卵巢上皮性癌中的表达特点及与血管内皮生长因子(VEGF)和血管生成的关系.方法 应用免疫组化P-V6000二步法检测62例卵巢上皮性癌、30例卵巢良性肿瘤和20例正常卵巢组织中APE/Ref-1和VEGF的表达,采用血管内皮特异标记物CD34标记并计数微血管密度(MVD),最后分析APE/Ref-1与VEGF和MVD的关系.结果 良恶性卵巢肿瘤和正常卵巢组织中都有APE/Refo-1表达,但是定位有所不同:20例正常组织只在细胞核中表达;30例良性肿瘤和62例癌组织都存在细胞核表达,但良性肿瘤中4例存在胞质表达,癌组织中48例存在胞质表达,且胞质APE/Ref-1阳性表达的癌组织较无表达者VEGF阳性率显著增加(P<0.05),MVD也显著增加(P<0.05),且细胞核和细胞质中APE/Ref-1的表达都与临床分期关系密切.结论 卵巢癌中APE/Ref-1的胞质移位可能与卵巢癌的发生有关,并且与VEGF的高表达和血管生成关系密切.     

卵巢癌与血管内皮生长因子有关

第四军医大学西京医院妇产科主治医师严瑞兰等完成的一项国家自然科学基金资助项目证明,血管内皮生长因子在与上皮性卵巢癌有关的血管形成中起重要作用。严瑞兰等采用免疫组化方法检测了３７例上皮性卵巢癌中血管内皮生长因子表达。结果显示,上皮性卵巢癌、交界性卵巢肿瘤及良性肿瘤中血管内皮生长因子表达率分别为７２．９％、７５．０％及３８．４６％,恶性肿瘤及交界性肿瘤中血管内皮生长因子表达率较良性肿瘤明显增高（Ｐ＜０．０５;上皮性卵巢癌,交界性卵巢肿瘤中血管内皮生长因子强阳性表达率分别为４５．９５％、４３．７５％,…     

卵巢癌组织中VEGF及MVD表达及其临床意义

目的 分析微血管密度(MVD)以及卵巢上皮性肿瘤血管内皮生长因子(VEGF)的表达与卵巢癌临床病理因素的关系及两者的相关性.方法 选取手术切除的卵巢上皮性肿瘤标本88例以及正常卵巢组织标本35例,采用免疫组化染色方法检测所有标本中VEGF及MVD的表达情况,分析两者相关性及与卵巢上皮性肿瘤临床病理因素的关系.结果 VEGF在卵巢癌组织中的表达阳性率为92.0％及MVD平均值为(30.26±8.69),显著高于良性卵巢上皮性肿瘤组织VEGF的阳性表达率[52.6％,(11.52±3.46)] (P ＜0.05);而良性卵巢上皮性肿瘤组织中VEGF阳性表达率及MVD平均值均高于正常对照组(P＜0.05).VEGF阳性表逸的卵巢癌组织中MVD平均值显著高于VEGF阴性表达者,VEGF阳性表达与MVD平均值呈正相关(P＜0.05).卵巢癌组织中VEGF阳性表达与肿瘤临床分期及细胞分化程度存在明显相关性(P＜0.05),而与肿瘤直径、组织学类型以及患者年龄无明显相关性(P＞0.05).MVD与肿瘤临床病理特征无明显相关性(P＞0.05).结论 VEGF及MVD均能反映卵巢上皮性肿瘤的良恶性和恶性进展程度,并可能成为卵巢癌临床生物学治疗的参考指标.     

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.     

P16 P15及VEGF蛋白在原发性卵巢癌中的表达及临床意义

  目的   探讨P16、P15及血管内皮生长因子(VEGF)在原发性卵巢癌中表达情况及其与临床病理特征的关系。   方法   采用免疫组织化学S-P法对170例原发性卵巢癌、60例交界性肿瘤及60例良性肿瘤组织进行P16、P15和VEGF蛋白检测。   结果   P16在卵巢癌的表达率为40.0%(68/170), 明显低于良性肿瘤组65.0%(39/60)和交界性肿瘤组56.7%(34/60)(P < 0.05);P15在卵巢癌组的阳性表达率为45.3%(77/170), 显著低于良性肿瘤组68.3%、交界性肿瘤组61.7%(37/60)(P < 0.05);VEGF在卵巢癌组的阳性表达率为71.2%(14/170), 明显高于良性肿瘤组45.0%(27/60)和交界性肿瘤组53.3%(32/60)(P < 0.05)。在卵巢癌组中, P16和P15表达呈正相关(r=0.294, P < 0.01), VEGF与P16和P15的表达呈负相关(r值分别为-0.461和-0.251, P < 0.01)。三者表达强度与肿瘤分化程度、临床分期、淋巴结转移有显著相关性, 肿瘤分化越低、临床分期越高、淋巴结转移者P16、P15阳性表达率越低(P < 0.05), VEGF阳性表达率越高(P < 0.05)。P16和P15的表达与有无脉管瘤栓无关, VEGF在有脉管瘤栓组的表达高于无脉管瘤栓组。   结论   P16和P15的低表达与VEGF蛋白高表达在卵巢癌的发展过程中可能起协同作用, 共同促进卵巢癌的恶性发展进程。      

血管内皮生长因子mRNA在上皮性卵巢癌中的表达及意义

目的 探讨血管内皮生长因子（vascular endothelial growth factor, VEGF） 核酸在上皮性卵巢癌组织中的表达及其与临床、病理特性之间的联系。方法上皮性卵巢癌31例，卵巢上皮性良性肿瘤17例及正常卵巢组织5例,采用原位杂交技术显示各类卵巢组织中VEGF mRNA的表达水平。结果上皮性卵巢癌组织的VEGF mRNA阳性表达率为48.39%（15/31）,显著高于良性肿瘤（P〈0.05）。上皮性卵巢癌中VEGF mRNA阳性表达率与淋巴结转移与否及腹水量密切相关（P〈0.05）。上皮性卵巢癌不同组织类型、病理分级及临床分期等指标均与VEGF mRNA阳性表达率无明显相关性（P〉0.05）。上皮性卵巢癌的预后与其组织中 VEGF mRNA阳性表达率亦无相关性（P〉0.05）。结论 VEGF mRNA在上皮性卵巢癌中的表达水平显著升高,且与淋巴结转移与否及腹水量密切相关，可作为卵巢癌侵袭性评估的指标之一。     

High expression of vascular endothelial growth factor is associated with liver metastasis and a poor prognosis for patients with ductal pancreatic adenocarcinoma

BACKGROUND: Vascular endothelial growth factor (VEGF), a recently identified growth factor with significant angiogenic properties, is a multifunctional angiogenic cytokine that is expressed in many tumors. High VEGF expression has been shown to correlate with the incidence of metastasis and poor prognosis in various cancers. In this study, the authors investigated VEGF expression and microvessel density (MVD) in ductal pancreatic adenocarcinoma and examined the correlations among VEGF expression, clinicopathologic factors, and clinical outcome. The authors especially focused on the correlation between VEGF expression and liver metastasis. METHODS: Paraffin embedded tumor specimens of 142 surgically resected pancreas carcinoma were immunohistochemically stained for VEGF and MVD. The correlations among VEGF expression and MVD, clinicopathologic factors, and clinical outcome were then statistically analyzed. RESULTS: One hundred thirty-two (93%) of 142 ductal pancreatic adenocarcinomas were positive for VEGF protein by immunohistochemistry. A significant correlation was observed between VEGF positivity and MVD (P < 0.0001). Multivariate logistic regression analysis indicated a significant association between high VEGF expression and liver metastasis (P = 0.010) but no other factors, such as age, tumor size, histologic type, lymph node metastasis, venous invasion, neural invasion, peritoneal metastasis, or local recurrence. Patients with tumors that showed moderate or high VEGF expression had significantly shorter survival than patients with low VEGF expression or none at all in their tumors (P < 0.05). CONCLUSIONS: These results indicate that VEGF expression is closely correlated with MVD and seems to be an important predictor for both liver metastasis and poor prognosis in ductal pancreatic adenocarcinoma.     

Vascular endothelial growth factor activating matrix metalloproteinase in ascitic fluid during peritoneal dissemination of ovarian cancer

The role of vascular endothelial growth factor (VEGF) during peritoneal dissemination of ovarian carcinoma and the association with tumor microvessel density (MVD) and matrix metalloproteinase (MMP) activity was investigated. To this end, MVD, tumor tissue and ascitic fluid levels of VEGF, and MMP activity of ascitic fluid were examined in patients with ovarian cancer and benign ovarian tumor. The effect of ascites on cell growth, cell invasion activity and angiogenesis was investigated in vitro. Ascitic fluid and tumor tissue samples were obtained from 15 patients with benign ovarian tumor and 24 patients with ovarian carcinoma. Tissue extract and ascitic fluid levels of VEGF were measured using enzyme immunoassay. Tumor microvessels were detected immunohistochemically. MMP activity was measured by gelatin zymography. For the in vitro experiment, the SKOV-3 human ovarian carcinoma cell line was utilized. Cell growth was examined using MTT-assay, cell invasion activity was measured by Matrigel in vitro invasion assay, and neovascularization was assessed using an angiogenesis kit. VEGF levels in tissue extract and ascitic fluid, MVD, expression of active form MMP-2 in ascitic fluid and ascites volume were higher in ovarian cancer patients than in benign ovarian tumor patients. In addition, these were elevated in stage III and IV diseases compared to stage I and II diseases in ovarian cancer patients. MVD and expression of active form MMP-2 in ascitic fluid were closely correlated with VEGF level in tissue extracts, and MVD and ascites volume were closely correlated with VEGF level in ascitic fluid. Cell invasive activity and angiogenesis activity increased when cells were exposed to ascites. These increases were apparent when exposed to ascites obtained from ovarian cancer patients and were related to VEGF concentrations of ascitic fluid and expression of active form MMP-2 in ascitic fluid. The increased VEGF secreted from tumor cells is suggested to enhance tumor growth through angiogenesis, to produce ascites and to elevate ascitic VEGF concentrations and expression of active form MMP-2. The progression of peritoneal involvement may be induced by elevated VEGF and expression of active form MMP-2, followed by increased VEGF in the primary tumor. Control of VEGF in the primary tumor may become an effective strategy against peritoneal dissemination of ovarian carcinoma.     

VEGF、CD31及MVD在卵巢上皮癌中临床意义

[目的]评价VEGF、CD31和MVD在卵巢癌中的表达及临床意义。[方法]卵巢上皮癌40例及正常卵巢组织20例标本采用免疫组织化学方法检测VEGF和CD31的表达，并计数MVD。[结果]卵巢癌中VEGF阳性表达率为67．5％，明显高于对照组的15．0％。有淋巴结转移者的VEGF和MVD明显高于无转移者（P〈0．05）：Ⅲ～Ⅳ期病例的VEGF和MVD也明显高于Ⅰ～Ⅱ病例（P〈0．05）。[结论]VEGF、CD31在卵巢癌的发生发展中起着重要的作用。MVD与肿瘤的浸润和转移相关。     

Intratumoral neovascularization and growth pattern in early gastric carcinoma.

BACKGROUND: The growth pattern of early gastric carcinoma, based on a volumetric analysis, reflects biologic characteristics of the tumor. The authors investigated the microvessel density (MVD), expression of vascular endothelial growth factor (VEGF), and growth patterns in early gastric carcinoma. METHODS: Ninety-four tissue specimens resected from patients with early gastric carcinoma invading the submucosal layer were examined. Microvessel quantification was performed immunohistochemically using a monoclonal antibody against factor VIII-related antigen. VEGF expression was studied using an anti-VEGF polyclonal antibody. Growth patterns were defined as follows: Pen A type: expansively penetrating growth; Pen B type: infiltratively penetrating growth; Super type: superficially spreading growth. RESULTS: The mean MVD was 16.9 (range, 5.2-43.0). MVD was significantly higher in tumors with venous invasion (P<0.01), lymphatic vessel invasion (P<0.05), and lymph node metastases (P<0.05) compared with MVD in tumors without venous or lymphatic vessel invasion or lymph node metastases. The VEGF-positive rate of Pen A type tumors was 66.7% (18 of 27), that Pen B type was 10.0% (1 of 10), that of Super type was 19.4% (6 of 31), and that of the unclassified type was 15.4% (4 of 26). The VEGF-positive rate in patients with Pen A type tumors was significantly higher than that in patients with the other three growth patterns(P<0.01). MVD in patients with Pen A type tumors (25.9+/-9.2) was significantly higher than that in patients with Super type tumors (12.6+/-5.4) (P<0.01). Patients with Pen A type tumors had a poorer prognosis than patients whose tumors had other growth patterns (P<0.05). According to multivariate analysis, VEGF expression and lymphatic vessel invasion were significant prognostic factors. CONCLUSIONS: Pen A type gastric carcinoma tends to secrete VEGF, thus inducing tumor angiogenesis and resulting in venous invasion. Intensive follow-up is necessary for patients with Pen A type tumors, because this tumor type has a greater propensity for hematogenous metastasis.