腋淋巴结阴性乳腺癌血管生成与预后相关性研究

】 ObjectiveTo determine the relation of microvessel density (MVD) and the expression of vascular endothelial growth factor (VEGF) with the prognosis of axillary-node-negative breast carcinoma (ANNBC) for searching for new prognostic factors. MethodsEighty specimens resected from patients with ANNBC were investigated by staining with a monoclonal antibody against FVⅢ-RA and polyclonal antibody against VEGF. Correlations between the expression of VEGF,MVD and several of clinicopathologic factors were studied. ResultsThe mean of MVD was 35.99± 20.27 in all patients.The positive rate of VEGF was 36.25％ . Both of them were not correlated with the clinicopathological factors. MVD was significantly higher in VEGF-positive tumors or relapsed or metastatic group than in VEGF-negative tumors or disease-free survival group. Moreover, patients with higher MVD or VEGF positive tumors had lower disease-free survival (DFS) or overall survival (OS) than those with lower MVD or VEGF-negative tumors. When those (45 cases) without adjuvant therapies after surgery were analyzed, the results were the same.But OS of them (35 cases) with adjuvant therapies had no significiant difference between high and low MVD group,and between VEGF positive and negative group. DFS was the same among VEGF positive and negative group. Multivariate analysis indicated that MVD,the expression of VEGF and tumor size were independent prognostic factors in patients with ANNBC. ConclusionsMVD,the expression of VEGF may be good prognostic indicators for patients with ANNBC and adjuvant therapies after surgery or antiangiogenic therapy may be useful to improve the prognosis of patients with high MVD or VEGF-positive tumors.     

Analysis of p53 and vascular endothelial growth factor and its receptor Flk-1 expression in human gallbladder carcinoma for determination of tumor vascularity

Objective： More and more studies have demonstrated that the p53 tumor suppressor gene plays an important role in controlling tumor angiogenesis. There is some evidence that p53 mutations cause overexpression of vascular endothelial growth factor （VEGF）, a major inducer of angiogenesis. In addition, there is now growing evidence that several malignancies express receptors for VEGF, especially receptor-2 （Flk-1/KDR）, raising the possibility that the VEGF/VEGF receptor axis may serve as an autocrine pathway in some tumors. We examined the expression of p53 and VEGF and its receptor FlK-1, together with microvessel count （MVC） to investigate the role of VEGF as an angiogenic marker, the presence of VEGF/Flk-1 axis, and the possible role of p53 in the regulation of angiogenesis in human gallbladder carcinoma. Methods： Surgically resected specimens of 49 gallbladder carcinomas were studied by immunohistochemical staining for p53 protein, VEGF, Flk-1 and factor VIII-related antigen. VEGF expression and mutant p53 expression were then correlated with Nevin stage, differentiation grade, MVC, and lymph nodes metastasis. Results： VEGF, Flk-1 expression and positive p53 protein accumulation and BEGF expression was found in 63.3%, 67.3% and 61.2% of tumors, respectively. The expression of Flk-1 was markedly correlated with VEGF （P〈0.05）. The percentage of the patients with both positive VEGF and Flk-1 expressions was 49.0% （24/49）, and their MVC value was markedly higher than that of the others. P53 and VEGF staining status were identical in 55.1% of tumors. The Nevin staging of p53-or VEGF-positive tumors was significantly later than negative tumors. The MVC in p53-or VEGF-positive tumors was significantly higher than that in negative tumors, and MVC in both p53- and VEGF-negative tumors was significantly lower than that in the other subgroups. Conclusion： The findings suggest the VEGF/F1 k- 1 axis and p53-VEGF pathway tumor angiogenesis in human gallbladder carcinoma. Combined analysis of p53 and VEGF expression, plus Flk-1 and VEGF expression might be useful for predicting the tumor vacularity and biologic behaviors of gallbladder cancer.     

良恶性前列腺疾病肿瘤血管形成的MR灌注加权成像评价

Objective: To explore the application of MR perfusion-weighted imaging (PWI) in the benign and malignant prostate diseases, and evaluate the correlations of PWI features with vascular endothelial growth factor (VEGF) and microvessel density (MVD). Methods: Seventy-four consecutive patients who were diagnosed clinically for the prostate diseases, including forty-four cases with benign prostate hyperplasia and thirty cases with prostatic cancer proved pathologically, were examined by PWI. MVD and VEGF were stained with immunohistochemical methods. Some parameters of PWI, including the steepest slope of signal intensity-time curve (SSmax) and the change in relaxation rate (△R2* peak) at lesions, were analyzed.Correlation analysis was used to determine the relationship between the results of PWI and immunohistochemistry. Results:(1) In the benign prostate hyperplasia (BPH), SSmax and △R2* peak of perfusion curve were 34.2 2.9 and 1.49±0.11,respectively; however, in the prostatic cancer (Pca), they were 58.6±4.8 and 3.18 0.49 respectively; there were statistical differences (t = 2.16 and 2.31, P ＜ 0.05). (2) The VEGF and MVD expressions of thirty Pca patients were significantly higher than those of forty-four BPH patients (X2 = 28.64, P＜0.01; t = 21.2, P＜0.01). MVD expressions of Pca and BPH groups showed positive associations with VEGF expressions (P＜0.01). On MR perfusion-weighted imaging, SSmax and △R2* peak showed associations with MVD and VEGF expressions (P＜0.01). Conclusion: On MR perfusion-weighted imaging, SSmax and △R2* peak can reflect MVD and VEGF expression levels in the benign and malignant prostate diseases and might be implied the tumor angiogenesis so as to distinguish benign from malignant and provide the important information for the surgeon to diagnose and treat the prostatic diseases.     

Vascular Endothelial Growth Factor Expression in Invasive Ductal Carcinoma of Breast

Objective： To detect the expression of VEGF and MVD count in invasive ductal carcinoma of breast to clarify the association of VEGF expression and MVD count with the clinicopathologic features. Methods： The expressions of VEGF, ER, PR, C-erbB-2 and MVD count in 88 cases of invasive ductal carcinoma of breast were examined by immunohistochemistry staining （SP-method）. Results： Sixty-two out of the eighty-eight specimens of breast carcinoma （70.45%） showed positive expression of VEGF. The positive rate of VEGF in cases with lymph node metastasis was higher than that without lymph node metastasis （P〈0.05）. The positive rate of VEGF in stage IIb-Ⅲ was higher than that in stage Ⅰ-Ⅱa （P〈0.05）. The positive rate of VEGF in C-erbB-2 positive group was higher than that in C-erbB-2 negative group （P〈0.05）. Higher expression of VEGF was observed in cases with higher tissue differentiation degree （P〈0.05）. Also, significant higher MVD count was observed in cases with higher tissue differentiation degree （P〈0.01）. The MVD count increased significantly with the increase of the expression of VEGF （P〈0.01）. Conclusion： The result of this study suggested that in invasive ductal carcinoma of breast, angiogenesis and metastasis were mediated mainly by VEGF. The expression of VEGF and MVD might be reference predictors for the biological behavior of breast carcinoma. The antiangiogenic therapy which used VEGF as a target would become a new method to treat patients who were C-erbB-2 positive in the future.     

环氧化酶-2对鼻咽癌血管生成及预后的影响

Objective： The purpose of this study was to evaluate cyclooxygenase-2 （COX-2） expression in nasopharyngeal carcinoma （NPC） and its correlation with clinicopathologic features, angiogenesis, and prognosis. Methods： The expressions of COX-2 and vascular endothelial growth factor （VEGF） and microvascular density （MVD） were determined with immunohistochemical methods in eighty-six NPC patients followed up over 5 years. Results： Sixty-three tumors （73.3%） were classified as COX-2 positive. COX-2 expression was positively related to VEGF expression （r=0.438, P〈0.01） and correlated with the tumor pathological grade, extent of primary lesion, lymph node metastasis, distant metastasis and shorter survival. Conclusion： Our results suggest that COX-2, being highly expressed and strongly correlated with angiogenesis in nasopharyngeal carcinoma, is apt to be used as a predictor of prognosis, including local recurrence and distant metastasis.     

Expression and clinical significance of vascular endothelial growth factor in benign and malignant tissues of breast

Objective:To detect the expression of vascular endothelial growth factor(VEGF)and microvessel density(MVD)count in breast benign affection,breast atypical hyperplasia and breast carcinoma in situ,and to clarify the relationship between VEGF expression,MVD and the clinicopathological features of these diseases. Methods:The expression of VEGF and MVD count in 115 cases breast benign diseases(including 40 breast fibroid tumor,40 breast cystic hyperplasia and 35 intraductal papilloma,19 breast atypical hyperplasias and 32 breast carcinomas in situ were examined by immunohistochemistry staining(SP-method). Results:The positive rate of VEGF in breast benign diseases,breast atypical hyperplasia and breast carcinoma in situ were 21.74%(25/115)、31.58.%(6/19)and 53.13%(17/32)respectively.It was the lowest in breast benign affection group,and was the highest breast carcinoma in situ group.The expression of VEGF increased gradually in the three groups(P＜0.05).The MVD count of the three groups were 14.41±2.59,18.89±4.47 and 21.13±4.12 respectively,It was the lowest in breast benign affection group,and was the highest breast carcinoma in situ group.The MVD count of the three groups increased gradually(P＜0.05).In VEGF positive group,MVD count was 19.41±4.78;In VEGF negative group,MVD count was 14.91±3.15.The MVD count was higher in VEGF positive group than that in VEGF negative group(P＜0.05). Conclusion:The results of this study suggested that VEGF could promote microvessel growth in breast tumors.The occurrence and progression of breast cancer might be related with the expression of VEGF.     

Anti-tumor effect and its mechanisms of ursolic acid on human esophageal carcinoma cell Eca-109 <Emphasis Type="Italic">in vivo</Emphasis>

Objective： To investigate the anti-tumor effect and possible mechanisms of ursolic acid on human esophageal carcinoma in vivo. Methods： Atransplanted tumor model by injecting Eca-109 cells into subcutaneous tissue of BALB/c nude mice was established. 40 nude mice bearing tumors were randomly divided into 4 groups and 0.2 ml saline or 0.2 ml ursolic acid （25-100 mg·kg^-1·d^-1） was injected into abdominal cavity respectively once everyday and lasted for fourteen days. The changes of tumor volume were measured continuously and tumor inhibition rate was calculated. The morphological changes of apoptosis were observed by electron microscope. The expressions of COX-2, bcl-2 and Bax protein in transplanted tumors were detected by immunohistochemistry. At last the PGE2 level of transplanted tumors was detected byradioimmunoassay. Results： Treatment of nude mice with 25, 50, or 100 mg·kg^-1·d^-1 of ursolic acid significantly inhibited the growth of the human esophageal carcinoma tumor in nude mice and induced Eca-109 cells apoptosis as demonstrated by electron microscopy analyses. The expressions of COX-2 and bcl-2 in the transplanted tumors were decreased in ursolic acid groups, while the Bax increased. The PGE2 level of transplanted tumors was decreased in ursolic acid groups with adose-relatedmanner. Conclusion： Ursolic acid has anti-tumor effects against human esophageal carcinoma cells in vivo, which are likely mediated via induction of tumor cell apoptosis and inhibition of COX-2 and PGE2.     

Anti-Tumor Effect of Curcumin on Human Cervical Carcinoma HeLa Cells In Vitro and In Vivo

Objective: To investigate the anti-tumor effect of curcumin on human cervical carcinoma HeLa cells in vitro and in vivo. Methods: (1) Human cervical carcinoma cell line HeLa was cultured in vitro. HeLa cells were treated with 5-50 μmol/L curcumin for 24. 48, 72 h and the growth inhibition rates of HeLa cells were measured by MTT method. Cell apoptosis was inspected by electron microscopy and flow cytometry (FCM). (2) A transplanted tumor model by injecting HeLa cells into subcutaneous tissue of BABL/C mice was established and its growth curve was measured. 30 BABL/C mice with tumors were divided into 2 groups at random and 0.2 ml saline or 0.2 ml 250 μmol/L curcumin was injected into abdominal cavity respectively once everyday and lasted for ten days. The changes of tumor volume were measured continuously and tumor inhibition rate was calculated. At last the expressions of caspase-3 and bax protein in transplanted tumors were detected by immunohistochemistry. Results: (1) Curcumin inhibited the proliferation of Lela cells on a dose-depending manner. Apoptosis of cells could be observed by FCM. Partial cells presented the characteristic morphological changes of apoptosis under electron microseope. (2) When 1×107 HeLa cells were inoculated for each mouse, 100% of the mice developed growing tumors after seven days. An inhibition effect was observed in treatment group, and the inhibition rate of curcumin was 74.33%. The expressions of caspase-3 and bax in the transplanted tumors were increased in curcumin group. Conclusion: Curcumin is effective as an anti-cancer drug not only in vitro but also in vivo.     

脑星形细胞肿瘤中FAK、Pyk2表达及其与血管生成的关系

背景与目的：非受体酪氨酸蛋白激酶家族成员FAK和Pyk2具有高度同源性,对肿瘤细胞增殖和侵袭具有重要的调控作用,但其是否参与肿瘤血管生成过程尚不明确。本研究旨在探讨FAK和Pyk2在脑星形细胞肿瘤中表达与血管生成的关系。方法：应用免疫组化法检测58例脑星形细胞肿瘤中FAK、Pyk2和血管内皮生长因子（VEGF）表达,并用CD31标记计数瘤内微血管密度。结果：FAK、Pyk2蛋白主要表达于肿瘤细胞胞浆,Pyk2阳性表达也见于肿瘤血管内皮细胞。在Ⅰ、Ⅱ、Ⅲ、Ⅳ级星形细胞肿瘤中,FAK阳性率分别为20.0%（1/5）、26.7%（4/15）、44.4%（8/18）、50.0%（10/20）,Pyk2阳性率分别为40.0%（2/5）、60.0%（9/15）、77.8%（14/18）、85.0%（17/20）;FAK和Pyk2阳性表达强度评分在Ⅱ级星形细胞肿瘤与Ⅲ、Ⅳ级星形细胞肿瘤中具有显著差异性（P〈0.05）。FAK、Pyk2表达与VEGF和微血管密度呈正相关,相关系数分别为rs=0.423（P=0.001）和rs=0.729（P〈0.005）。结论：FAK、Pyk2可能通过与VEGF的相互作用而参与脑星形细胞肿瘤的血管生成过程。     

促血管生成素表达与人脑胶质瘤血管生成的关系研究

目的:研究促血管生成素(angiopoie-tins,Angs)蛋白表达水平与血管内皮生长因子(vascular endothelial growth factar,VEGF)和肿瘤内微血管密度(microvascular density,MVD)的关系,探讨其在人脑胶质瘤血管生成中的作用。方法:采用免疫组化方法检测42例人脑胶质瘤组织中Ang-1、Ang-2和VEGF的蛋白表达水平,并以抗CD34单克隆抗体显示血管内皮细胞,根据CD34阳性的血管计数来判定MVD。结果:42例人脑胶质瘤中,Ang-1+肿瘤的MVD比Ang-1-肿瘤高,但两者差异无统计学意义,P=0·156;Ang-2-和Ang-2+平均MVD分别是27·67和49·63,Ang-2+肿瘤MVD显著高于Ang-2-肿瘤,P=0·000。VEGF阳性表达时,Ang-2+肿瘤平均MVD显著高于Ang-2-肿瘤,分别为56·00和36·75,P=0·001;而VEGF阴性组中,Ang-2+肿瘤平均MVD与Ang-2-肿瘤几乎相等,分别为53·17和47·36,P=0·109。随胶质瘤恶性程度增加,Ang-1和Ang-2阳性表达率均升高,但Ang-2升高更明显,不同级别间Ang-2表达水平差异有统计学意义。结论:Ang-2高表达与人脑胶质瘤血管新生密切相关,Ang-2可以作为评价胶质瘤血管生成及恶性程度的一个重要指标。VEGF存在时,Ang-2过表达可促使肿瘤血管生成。肿瘤防治杂志,2005,12(19):1472-1475     

人肝癌组织中iNOS、VEGF的表达及微血管密度的病理意义

背景与目的:诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)和血管内皮生长因子(vascular endothelial growth factor,VEGF)被认为是诱导和调节肿瘤血管生成,进而影响肿瘤病理进展和预后的重要相关因子。本研究检测人肝细胞癌(hepatocellular carcinoma,HCC)及相应癌旁组织中iNOS、VEGF的表达,探讨其与血管生成的关系,为临床诊治HCC及判断其预后提供理论依据。方法:应用组织芯片技术,采用原位杂交和免疫组化法分析147例HCC组织及癌旁组织中iNOS、VEGF的表达,并用CD34标记免疫组化法检测微血管密度(microvessel density,MVD)。结果:iNOS、VEGF在癌旁组织中的阳性率分别为33.33%和40.82%,而在癌组织中的阳性率分别为86.39%和78.91%,癌组织与癌旁组织比较差异有显著性(P<0.01)。癌组织的MVD值为56.5±12.8,癌旁组织的MVD值为8.4±3.6,两者差异有显著性(P<0.01)。iNOS的表达与肿瘤大小、乙型肝炎表面抗原(HBsAg)相关(P<0.05),而与转移和肿瘤分化程度无关(P>0.05)。VEGF的表达及MVD值与肿瘤大小、转移相关(P<0.05),而与HBsAg和肿瘤分化程度无关(P>0.05)。在癌组织中MVD与VEGF、iNOS的表达呈正相关,VEGF和iNOS之间亦存在正相关关系(P<0.01)。结论:HCC中iNOS及VEGF的表达与肿瘤血管生成有关。癌组     

Angiopoietin 2 expression in invasive ductal carcinoma of the breast: its relationship to the VEGF expression and microvessel density

Summary Angiopoietin (Ang) is a ligand for the endothelium-specific tyrosine kinase receptor Tie-2, while a shift in the Ang-1:Ang-2 expression ratio in favor of Ang-2 was found to be associated with tumor angiogenesis. In the present study, we analyzed the immunohistochemical expression of Ang-2 in a series of 198 breast cancers, in which VEGF expression and microvessel density (MVD) were previously determined. Ang-2 expression was negative in 24 (12%), positive in 50 (25%) and strongly positive in 124 (63%) of 198 cases. A significant correlation was found between Ang-2 and VEGF expressions (p=0.0004) and between Ang-2 expression and MVD (p=0.0006), while a high MVD was found in 10 (77%) of 13 tumors with a strongly positive VEGF and positive Ang-2 expression and in 40 (71%) of 56 tumors with a strongly positive VEGF and strongly positive Ang-2 expression. Although there was no difference in the disease free survival (DFS) stratified according to Ang-2 expression alone, the 69 patients with a strongly positive VEGF and a strongly positive or positive Ang-2 expression had a significantly (p=0.0316) worse DFS than those with other combinations of VEGF and Ang-2 expressions. A multivariate analysis indicated lymph node metastasis and MVD to be independently significant prognostic factors for DFS, while the combination of VEGF and Ang-2 expressions was not a significant factor for DFS. In conclusion, the Ang-2 expression was found to be closely correlated with VEGF expression and MVD in breast cancer, while a high MVD was frequently found in tumors with a high expression of both VEGF and Ang-2. The survival analysis demonstrated a high MVD, which was induced by a high expression of both VEGF and Ang-2, to therefore have a strong prognostic significance in breast cancer.     

肝细胞癌p53和VEGF的表达及其与肿瘤血管形成的关系

目的 :研究p5 3和血管内皮生长因子 (vascularendothelialgrowthfactor ,VEGF)的表达和肿瘤微血管密度 (microvesseldensity ,MVD)测定在人肝细胞癌 (HCC)中的意义。方法 :采用免疫组织化学方法 ,检测 5 0例HCC患者手术切除标本p5 3和VEGF的表达 ,并用抗CD3 4 抗体标记癌组织血管内皮细胞 ,计算MVD。结果 :p5 3、VEGF总阳性表达率分别为 5 4 0 % (2 7 5 0 )和 76 0 % (38 5 0 ) ,p5 3、VEGF的表达和MVD均与HCC组织病理分级呈正相关 ,P <0 0 5。p5 3和VEGF的阳性表达符合率为 74 % (37 5 0 ) ,两者的表达呈相关性 ,P <0 0 5。p5 3阳性和VEGF阳性的癌组织MVD分别为 178± 6 2和 175±5 9 ,而相应的阴性组分别为 12 5± 5 1和 131± 6 1,两者差异有显著意义 ,P <0 0 5。p5 3、VEGF表达均为阳性者 ,MVD为 176± 6 3;p5 3、VEGF的表达均为阴性者 ,MVD为 12 3± 5 2 ;两者差异有显著意义 ,P <0 0 5。结论 :1)p5 3、VEGF的表达以及MVD的测定可作为判断HCC恶性潜能的重要生物学指标 ;2 )p5 3、VEGF的表达对肿瘤血管形成可能起重要作用 ,联合检测p5 3、VEGF的表达对了解肿瘤血管形成的机制有一定意义     

尿纤溶酶原激活物及血管内皮生长因子在食管癌中的表达及对肿瘤血管形成的影响

目的探讨尿纤溶酶原激活物（uPA）、血管内皮生长因子（VEGF）在食管癌中的表达及对肿瘤血管生成的影响。方法采用免疫组织化学sP法检测正常食管黏膜上皮组织（18例）及食管癌组织（68例）中uPA、VEGF的表达,检测CD。用以标记肿瘤微血管密度（MVD）,根据MVD均值分为高、低MVD组,分析食管癌uPA、VEGF的表达和临床病理特征的关系及对肿瘤血管形成的影响。结果uPA蛋白在正常食管黏膜上皮组织、食管癌组织中的阳性率分别为27．8％（5／18）和70．6％（48／68）,差异有统计学意义（X^2=11．63,P〈0．05）;VEGF蛋白在正常食管黏膜上皮组织、食管癌组织中的阳性率分别为22．2％（4／18）和63．2％（43／68）,差异有统计学意义（X^2=9．78,P〈0．05）。食管癌组织中uPA与VEGF表达有一致性（X^2=9．72,P〈0．05）。MVD平均为42．38±11．62,高MVD组uPA、VEGF蛋白表达显著高于低MVD组（X^2值分别为6．13和10．12,均P〈0．05）。uPA、VEGF蛋白表达与年龄、性别、病理类型无关（均P〉0．05）,均与临床病理分期、分化程度和淋巴结转移相关（P〈0．05）。结论食管癌组织中uPA、VEGF蛋白高表达,可能促进肿瘤血管形成,提示预后不良。     

CEACAM1和VEGF在宫颈鳞癌组织中的表达及临床意义

目的 研究CEACAM1、VEGF和微血管密度(MVD)在宫颈癌组织中的表达与子宫颈癌的生长、浸润及转移的关系.方法 采用免疫组化二步法检测76例子宫颈鳞癌(高分化22例、中分化25例、低分化29例),15例宫颈上皮内瘤变(CIN)和10例正常宫颈组织中CEACAM1、VEGF的表达及CEACAM1标记的微血管密度.结果 在宫颈鳞癌组CEACAM1、VEGF及CEACAM1标记的MVD的表达与正常宫颈组织和CIN组差异有统计学意义(P<0.05),并且在宫颈鳞癌中的表达与盆腔淋巴结转移、组织学分级及FIGO分期有关(P<0.05),而与年龄无关(P>0.05).VEGF在宫颈癌中的表达与MVD的表达关系密切(P<0.01).结论 CEACAM1是一种肿瘤抑制因子,但其在肿瘤新生血管生成中起促进作用,VEGF可能在CEACAM1促进新生血管形成的过程中起到协同作用.     

Survivin、VEGF的表达及微血管密度与非小细胞肺癌临床病理特征的关系

背景与目的研究发现,Survivin在大多数肿瘤中有表达,但在成人组织不表达或低表达,且参与肿瘤血管形成。本研究中我们主要检测非小细胞肺癌(non鄄smallcelllungcancer,NSCLC)、癌旁及肺良性病变组织中凋亡抑制基因Survivin及血管内皮生长因子(vascularendothelialgrowthfactor,VEGF)的表达和微血管密度(microvesseldensity,MVD)值,并探讨三者间的相互关系。方法应用免疫组化(S鄄P)法检测96例NSCLC组织中Survivin、VEGF及MVD。分析Survivin、VEGF及MVD与NSCLC临床病理特征的关系,以及Survivin、VEGF、MVD间的相互关系。结果NSCLC组织中Survivin阳性率69.8%(67/96),明显高于癌旁(16.1%)和肺良性病变组织(0%)(P<0.01),其表达与肿瘤分化程度、TNM分期有关。VEGF在肺癌、癌旁、肺良性病变组织中的阳性率分别为72.9%(70/96)、45.2%(14/31)和25.0%(5/20)(P<0.05),其表达与肿瘤的TNM分期及淋巴结转移有关。肺癌、癌旁、肺良性病变组织中MVD值分别为24.44±7.79、19.37±5.26、11.83±6.25,且MVD值的高低与肿瘤大小、淋巴结转移和TNM分期有关(P<0.05)。Survivin在肺癌组织中的表达与VEGF、MVD密切相关,随着Survivin强度的增加VEGF分级及MVD值亦增加。结论不同性质的肺病变组织中Survivin、VEGF的表达水平和MVD值不同,NSCLC中Survivin表达明显增高,其表达与肿瘤分化、分期有关;Survivin的过度表达与NSCLC的血管生成有关,细胞凋亡与血管生成在肺癌的发生发展中起协调作用。     

塞来昔布对实验性结肠癌原位移植瘤生长及血管形成的影响

目的:探讨塞来昔布对实验性结肠癌原位移植瘤生长及血管形成的影响。方法:使用对数生长期的人结肠癌细胞(HT-29)于裸鼠皮下接种成瘤后原位种植。术后随机分为对照组(C组)及塞来昔布高、中、低剂量组(H、M、L组)共四组进行研究。结果:24只裸鼠实验期间无1只死亡,成瘤率为100%,比较各组原位移植瘤体积和瘤质量差异有统计学意义,P值均<0·05。L、M和H组的抑瘤率分别为25·30%、38·80%和76·92%,与对照组比较差异有统计学意义,P=0·000,且存在明显的剂量依赖。干预组瘤组织中MVD、VEGFmRNA、MMP-2mRNA和匀浆上清中PGE2含量与对照组相比差异有统计学意义,P值分别为0·050、0·050、0·050和0·010,随着剂量增加,MVD、VEGFmRNA、MMP-2mRNA和匀浆上清中PGE2含量逐渐降低。瘤组织中PGE2含量与瘤质量,以及MVD与VEGFmRNA、MMP-2mRNA均存在显著的正相关性,r=0·8814,P=0·000;r=0·8573,P=0·000;r=0·6427,P=0·001。结论:塞来昔布通过抑制人结肠癌裸鼠原位移植瘤环氧化酶-2活性,抑制PGE2合成、VEGFmRNA和MMP-2mRNA表达,抑制肿瘤的血管形成,从而对结肠癌的生长有抑制作用。