CORRELATIONS AMONG EXPRESSION OF ANGIOPOIETIN-1 TO CLINICAL PATHOLOGICAL CHARACTERISTICS AN ANGIOGENESIS IN ORAL SQUAMOUS CELL CARCINOMA

Objective： To study the expression and the significance of Angiopoietin-1 （Ang-1） through observing the correlations among the expression of Ang-1 to clinicopathologic characteristics and microvessel density （MVD） in oral squamous cell carcinoma （OSCC）. Methods： Expressions of Angiopoietin-1 and CD34 in 41 human OSCC tissues, 30 adjacent noncancerous oral tissues and 10 normal oral mucosas were detected by immunohistochemical SABC method. MCD was also assessed. Results： Of the 41 OSCC tissues, 41.46% （17/41） was Ang-1 positive. The expression of Ang-1 was significantly lower in OSCC than that in adjacent noncancerous oral tissues （P〈0.05） and normal oral mucosa （P〈0.05）. The Ang-1 expression was significantly higher in high differentiated tumor than that in moderately differentiated tumor （P〈0.05）. The MVD was significantly higher in Ang-1-negative OSCC than in Ang-1-positive OSCC （P〈0.01）, and negatively correlated with the expression of Ang-1 （r=-0.32, P〈0.05）. Conclusion： Down-regulated expression of Ang-1 may play a crucial role in the development of OSCC. It negatively regulated the angiogenesis of tumor.     

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.     

结直肠癌中CDX2、PTEN、Ki-67的表达及DNA倍体分析

Objective To investigate the expression of CDX2,PTEN and Ki-67 in colorectal carcinoma,and the correlations among CDX2,PTEN,Ki-67 and DNA ploidy. Methods Fifty samples of human colorectal carcinoma tissue and ten samples of normal mucosa adjacent to carcinoma were examined for CDX2,PTEN as well as Ki-67 by immunohistochmistry,and the flow cytometry was used to detect the status of DNA ploidy jn colorectal carcinoma.Results The expression of CDX2 in colorectal carcinoma and normal mucosa tissue were 82%(41/50) and 100%(10/10) respectively.The expression of CDX2 had significant difference compared to that in normal mucosa tissue.PTEN in colorectal carcinoma and normal mucosa were 64%(32/50)and 90%(9/10) respectively,the expression had significant difference.Both CDX2 and PTEN were related with staging and grading of tumor,metastasis of lymph nodes and infiltrating depth of carcinoma.Expression of CDX2 and PTEN was negatively correlated with the expression of Ki-67(r=-0.254,P＜0.05;r=-0.340,P＜0.01) respectively.The expression of CDX2 was increased in diploid colorectal cancer,as compared with that in heteroploidy colorectal cancer(93.75%and 76.47%).But the expression of PTEN had no difference between diploidy and heteroploidy carcinomas.Conclusion The expression of the CDX2 and of the PTEN were are positive in part of the colorectal carcinoma.Both CDX2 and PTEN's expression negatively correlate with Ki-67.CDX2,intestinal-specific homeobox genes,regulate cell proliferation and differentiation in the continuously renewed intestinal epitheium.PTEN positively regulates CDX2 gene expression.The down regulation of CDX2 protein is concerned with tumor maligancy and bad prognosis.     

EXPRESSION OF FLIP IN HUMAN COLON CARCINOMAS： A NEW MECHANISM OF IMMUNE EVASION

Objective： It has been proposed that Fas ligand （FasL） may play an important role in immune escape of tumors and FLIP is an important mediator of Fas/FasL pathway. In this study, the expression of FLIP was determined in human colon carcinoma cell lines and tissue to investigate the new mechanism of immune evasion of human colon carcinomas. Methods： RT-PCR and immunohistochemistry （IHC） were performed to investigate the expression of FLIP in human colon carcinoma cell lines SW480, LS174 and twenty human primary colon carcinoma specimens. Results： It was shown that SW480 cells, LS174 cells and primary colon carcinoma specimen constitutively expressed FLIP at the mRNA and protein level. The expression of FLIP was not found in the epithelial cells of normal colon mucosa. Conclusion： FLIP was expressed in human primary colon carcinoma specimens but not in the normal counterpart. It suggested that the expression of FLIP may occur during the malignant transformation from normal colon epithelial cells to colon carcinoma cells. Tumor cells might obtain the ability to resist the Fas-mediated apoptosis by expressing FLIP. The expression of FLIP might contribute to the formation of colon carcinomas.     

PDGF在子宫内膜癌中的表达及其与血管生成的关系

Objective:To investigate the expression of platelet-derived endothelial growth factor(PDGF) and its effect in angiogenesis in endometrial cancer(EC),in order to investigate the mechanism of tumorigenesis and lay a foundation for the management of EC.Methods:We selected 40 cases with EC,20 endometrium,and 20 normal endometrium.All specimens were stained immunohistochemically for CD34 and PDGF identified immunohistochemically with specific antibodies.Results:The expression of PDGF was significantly higher in EC than normal endometrium and atypical hyperplasia of endometrium(P < 0.05),however,no significant difference was found between normal endometrium and atypical hyperplasia of endometrium(P > 0.05).The expression of PDGF was lower in well differentiated than moderately and poorly differentiated EC(P < 0.05).In cases with muscular invasion tumors,it was higher than in normal endometrium(P < 0.05).After Spearman correlation analysis,MVD was significantly influenced by PDGF,r = 0.848(P = 0.000).Conclusion:There was positive correlation between microvessel density(MVD) and PDGF in earlier stage of EC,it illustrate that PDGF may take part in angiogenesis of EC.     

细胞外信号调节激酶在直肠癌发生发展中的意义

Objective： To study the ERK expression and its significance in the development of human rectal carcinoma. Methods： Samples were obtained from 62 patients with rectal carcinoma, including tumor tissue and adjacent normal rectal tissue. Western blot was used to measure the expression of ERK-1 and ERK-2. S-P immunohistochemical method was used to count the microvessel density （MVD）. Results： ERK-1 and ERK-2 protein levels were increased in rectal carcinoma tissue compared with those in adjacent normal tissues （t = 2.980 and 2.194, P 〈 0.01 and 0.05 respectively）. The MVD was higher in patients with higher ERK-1 and/or ERK-2 protein levels than that in cases with lower ERK-1 and/or ERK-2 levels. Conclusion： Overexpression of ERK-1 and/or ERK-2 may play an important role in the development of human rectal carcinoma, the overexpression can enhance the growth of tumor microvessel and promote the development of human rectal carcinoma.     

环氧化酶2和血管内皮生长因子在透明细胞性肾细胞癌中的表达及其与血管生成的关系

Objective To investigate the expression of COX-2 and VEGF in clear cell renal cell carcinoma(CCRCC)and their correlation with tumor angiogenesis.Methods Envision immunohistochemistry was used to determine the expression of COX-2 and VEGF,and microvessel density(MVD)was marked by CD34 in 80 CCRCC tissues and 20 normal kidney tissues.The relationship between the above mentioned markers were analyzed.Results Expressions of COX-2 and VEGF were noted in both CCRCC and normal kidney tissues.The positive rates of COX-2 and VEGF were significantly higher in CCRCC than in normal kidney(P ＜0.05);The expression of COX-2 was correlated with TNM stage(P ＜0.05),histological grade (P ＜0.05)and lymph node metastasis(P ＜0.05)in CCRCC,but not with age(P = 0.663)and diameter of tumor(P =0.528).Both COX-2 expression(r = 0.851,P ＜ 0.01)and VEGF expression(r = 0.736,P ＜ 0.01)were significantly associated with MVD in CCRCC.There was a positive correlation between expression of cox-2 and that of VEGF in CCRCC.Conclusion COX-2 expression is correlated with tumor angiogenesis in CCRCC.It is likely that VEGF is one of the most important mediators in the COX-2 angiogenic pathway.     

利用组织芯片技术研究胃癌及其癌前病变中Bax、p53、Survivin表达的关系及意义

Objective： To explore the relationship between expressions of apoptosis-related protein Bax, Survivin and p53 and the molecular mechanisms of carcinogenesis and progression of gastric carcinoma. Methods： Tissue microarray and immunohistochemistry were used in this study. Results： The positive rate of Bax protein in gastric cancer （17.7%, 17/96） was significantly lower than those in adjacent normal mucosa （51%）, intestinal metaplasia （69.2%） and dysplasia （75%）, P 〈 0.01. The positive rate of Survivin expression in gastric cancer （80.6%, 89/98） was significantly higher than that in adjacent normal mucosa （3.9%）, P 〈 0.01. The positive rates of Survivin expression in tumors with different organ metastases （in lymph node metastasis 86.2%, liver 100% and ovarian 100%） were statistically higher than in tumors without metastasis （64.3%）, P 〈 0.05. Bax expression was correlated with Survivin but not with rap53 that was closely related to Survivin expression （P 〈 0.05） in gastric cancer. Conclusion： The abnormal expressions of Bax, Survivin and rap53 were correlated with the tumorigenesis and progression of gastric carcinoma. P53 and Survivin genes may share the similar mechanism in regulating cell apoptosis, and because of the mutation, p53 gene may lower its down-regulation to Survivin expression.     

裸鼠肺癌移植瘤中NRP-1的表达及其意义

Objective:To establish angiogenesis model of xenografts of lung cancer cell in nude mouse and investigate the expression of the neuropilin-1 (NRP-1) protein in tumors and its role in progression and angiogenesis of lung cancer.Methods:Human lung adenocarcinoma cells A549 were analyzed for the expression of vascular endothelial growth factor165(VEGF165)mRNA using RT-PCR in vitro.TWo groups of nude mice were subcutaneously inoculated with A549 at different tumor-loading time.Two groups of xenografts were jdentified by hematoxylin and eosin (HE) staining.their microvessel density (MVD) were analyzed meanwhile.Two groups were analyzed for the expression of NRP-1 protein and their mean absorbency by using immunohistochemistry and automatic image analysis system respectively.Results:A549 expressed VEGF165 mRNA,and xenografts of A549 in nude mice were successfully established and confirmed by HE staining.The atypia of cancer cells and angiogenesis were occurred in two groups.Two groups of MVD were 13.06±1158.23.61±3.11(vessels/mm2)(P＜0.01).NRP-1 protein was expressed in cytoplasm of vascular endothelium cells and partial tumor cells.Two groups of mean absorbency of NRP-1 were 0.1095±O.0228,0.1784±0.0151 (P＜0.01).Conclusion:The angioqenesis models of xenografts in nude mice with lung cancer cell A549 expressing VEGF165 mRNA at different tumor-loading times were established successfully.The expression of NRP-1 protein and MVD were increased with the tumor progression.Our results demonstrate that NRP-1 protein in lung cancer is related to angiogenesis.     

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.     

促血管生成素及其受体的异常表达与胃癌血管生成的关系

目的探讨促血管生成素（Ang）及其受体Tie-2在胃癌中的表达及其与胃癌血管生成的关系。方法应用RT—PCR和免疫组化分析技术,检测68例胃癌组织及其相应的癌旁胃黏膜Ang-1、Ang-2及Tie-2 mRNA和蛋白表达水平,计数微血管密度（MVD）。结果胃癌组织及相应癌旁组织均见Ang—1、Ang-2及Tie-2 mRNA的表达,Ang-1蛋白、Tie-2 mRNA表达水平与MVD呈负相关（r=-0．440,r=-0．267;P〈O．05）,Ang-2 mRNA及蛋白表达水平与MVD呈正相关（r=0．319,r=0．729;P〈0．05）,Ang-2／Ang-1蛋白表达的比值与MVD呈正相关（r=0．739,P〈0．05）。在Ang-2 mRNAT／N比值（胃癌与癌旁胃粘膜mRNA表达水平的比值）〉1．2时,其MVD均高于T／N比值〈1．2者,而与Ang—1 mRNA的表达情况无关。结论Ang—1与Ang-2蛋白在胃癌血管生成中相互拮抗,Ang-2／Ang—1的比值可能是决定胃癌血管生成和肿瘤生长的最终因素。当Ang-2高表达而Ang-1低表达时,促进胃癌的血管生成;反之,则抑制胃癌血管生成。推测Angs及其受体系统在胃癌血管生成中的调节作用是以Ang-2的作用为主导的。     

血管生成素-2及其受体在卵巢癌组织中的表达及与血管生成的关系

目的探讨血管生成素-2（Ang-2）及其受体（Tie-2）在卵巢癌中的表达及与血管生成、临床病理特征的关系。方法采用RT-PCR法检测25例正常卵巢组织标本、25例良性卵巢肿瘤和65例恶性卵巢肿瘤中Ang-2及其受体Tie-2的表达水平,并采用免疫组织化学法检测各标本的微血管密度（MVD）。结果恶性组MVD显著高于良性组（t=2.61,P<0.05）,不同临床分期的卵巢癌MVD的差异有统计学意义（F=4.618,P<0.05）。恶性组Ang-2 mRNA阳性率和表达水平显著高于良性组和对照组（P<0.05）,不同临床分期的卵巢癌标本Ang-2 mRNA表达水平有显著性差异（0.298±0.022 vs.0.206±0086,P<0.05）。恶性组MVD与其Ang-2 mRNA表达水平呈正相关关系（rMV=0.685,P<0.05）。仅在5例恶性卵巢癌标本中检测到 Tie-2 mRNA表达,良性组和对照组未检出。结论恶性卵巢癌组织中高表达Ang-2,其与卵巢癌肿瘤血管大量形成有关。     

Ａｎｇ-１、Ａｎｇ-２和Ｔｉｅ-２表达在乳腺癌血管生成中的作用

目的　检测乳腺癌Ａｎｇ-１、Ａｎｇ-２及其受体Ｔｉｅ-２的表达水平,探讨三者在乳腺癌发生发展及血管生成中的调节作用。方法　采用免疫组化ＳＰ法对７９例乳腺癌标本、６８例癌旁组织及４２例乳腺纤维腺瘤组织中Ａｎｇ-１、Ａｎｇ-２、Ｔｉｅ-２及ＣＤ３４标记的微血管密度（ＭＶＤ）进行检测,分析它们与乳腺癌血管生成的关系。结果　Ａｎｇ-２及Ｔｉｅ-２在乳腺癌组织中的阳性表达率分别为７１.３％、６７.５％,明显高于癌旁组织的２１.６％、１９.２％和乳腺纤维腺瘤组织的２３.３％、１８.９％ （Ｐ＜０.０５）;Ａｎｇ-１在乳腺癌组织中的阳性表达率为１７.８％,明显低于癌旁组织的４８.６％及乳腺纤维腺瘤组织的５１.７％（Ｐ＜０.０５）。Ａｎｇ-２、Ｔｉｅ-２的表达与分期及腋窝淋巴结转移有关（Ｐ＜０.０５）。乳腺癌组织的ＭＶＤ为２５.６±９.８,明显高于癌旁组织的５.６±２.７和乳腺纤维腺瘤的６.９±３.１（Ｐ＜０.０５）。Ａｎｇ-１表达与ＭＶＤ呈负相关（ｒ＝－０.３９１,Ｐ＜０.０５）,Ａｎｇ-２、Ｔｉｅ-２的表达与ＭＶＤ均呈正相关（ｒ＝０.５８６,Ｐ＜０.０５;ｒ＝０.４１７,Ｐ＜０.０５）。结论　Ａｎｇ-１、Ａｎｇ-２和Ｔｉｅ-２在乳腺癌血管生成过程中发挥重要作用,并且Ａｎｇ-２、Ｔｉｅ-２的表达与乳腺癌的分期、腋窝淋巴结转移有关。     

促血管生成素-2对胃癌血管生成的双向效应

目的　探讨促血管生成素 2 (Ang 2 )在胃癌血管生成中的作用。方法　运用RT PCR和S P免疫组化方法检测Ang 2mRNA、血管内皮生长因子 (VEGF)、CD34蛋白在 36例胃癌及其相应癌旁胃黏膜组织中的表达。结果　胃癌组织及其相应癌旁胃黏膜组织均见有Ang 2mRNA阳性表达 ,胃癌组织Ang 2mRNA的总体表达水平与微血管密度 (MVD)未见明显相关。胃癌组织Ang 2mRNA表达水平低于癌旁胃黏膜组织者 2 7例 ,其癌组织中 ,Ang 2mRNA的表达水平与MVD呈正相关 (r=0 .4 11,P <0 .0 5 ) ;同时 ,VEGF阳性表达者的MVD(45 .4 5± 10 .30 )明显高于VEGF阴性染色者 (30 .15± 8.6 9,P <0 .0 5 ) ,即在Ang 2表达上调的情况下VEGF促进血管生成。胃癌组织Ang 2mRNA表达水平高于癌旁组织者 9例 ,其癌组织中Ang 2mRNA的表达水平与肿瘤组织的MVD呈负相关 (r =- 0 .75 8,P <0 .0 5 ) ,VEGF的阳性表达者与阴性染色者间 ,MVD差异无显著性 ,即Ang 2抑制血管生成与VEGF的表达无相关性。结论　Ang 2对胃癌血管生成具有双向调节作用。     

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.     

Ａｎｇ-１、Ａｎｇ-２和Ｔｉｅ-２表达与肝癌血管生成的关系

目的：检测血管生成素１（Ａｎｇ-１）、血管生成素２（Ａｎｇ-２）及其共同受体Ｔｉｅ-２在肝癌中的表达及与肝癌血管生成的关系。方法：采用免疫组化（ＳＰ法）对５３例肝癌标本、３０例癌旁组织及１０例正常肝组织中Ａｎｇ-１、Ａｎｇ-２、Ｔｉｅ-２及ＣＤ３１标记的微血管密度（ＭＶＤ）进行检测,分析它们与肝癌血管生成的关系。结果：Ａｎｇ-２及Ｔｉｅ-２在肝癌组织中的阳性表达率分别为６７.９％、７５.５％,明显高于癌旁组织４３.３％、４２.３％和正常肝组织２０.０％、２０.０％（Ｐ＜０.０５）;Ａｎｇ-１在肝癌组织、癌旁组织及正常肝组织中的阳性表达率无显著性差异（Ｐ＞０.０５）;ＣＤ３１标记的ＭＶＤ与Ａｎｇ-２、Ｔｉｅ-２表达密切相关。ＣＤ３１标记的ＭＶＤ与Ａｎｇ.２、Ｔｉｅ.２在肝癌组织中表达呈正相关（Ｐ＜０.０５）。结论：Ａｎｇ-１、Ａｎｇ-２和Ｔｉｅ-２的表达在调节肝癌的血管生成中可能起重要作用。     

Angiopoietins in angiogenesis

Tie-1 and Tie-2 tyrosine kinase receptors are expressed specifically on vascular endothelial cells and on a certain subtype of macrophages implicated in angiogenesis, thus, they have been a major focus of angiogenesis research. Tie-1 and Tie-2 are essential for vascular maturation during developmental, physiological and pathological angiogenesis. Angiopoietin 1–4 (Ang-1–4) have been identified as bona fide ligands of the Tie-2 receptor, while Tie-1 remains an orphan receptor which is able to heterodimerize with Tie-2 and to modulate Tie-2 signal transduction. The most exhaustively studied angiopoietins are Ang-1 and Ang-2. Ang-1 is a critical player in vessel maturation and it mediates migration, adhesion and survival of endothelial cells. Ang-2 disrupts the connections between the endothelium and perivascular cells and promotes cell death and vascular regression. Yet, in conjunction with VEGF, Ang-2 promotes neo-vascularization. Hence, angiopoietins exert crucial roles in the angiogenic switch during tumor progression, and increased expression of Ang-2 relative to Ang-1 in tumors correlates with poor prognosis. Its central role in the regulation of physiological and pathological angiogenesis makes the angiopoietin/Tie signaling pathway a therapeutically attractive target for the treatment of vascular disease and cancer.     

口腔鳞癌组织中Angiopoietin-1、Angiopoietin-2的表达及临床意义

背景与目的:近来研究表明Angiopoietin-1、Angiopoietin-2(Ang-1、Ang-2)是极有潜力的血管生长因子,它们与其它血管生长因子之间的局部平衡关系决定了血管是进展、稳定还是衰退。本文探讨Ang-1及Ang-2在口腔鳞癌中的表达及其与临床病理学特征和微血管密度(microvesseldensity,MVD)、血管成熟指数(vesselmaturationindex,VMI)之间的关系,并评估Ang-1及Ang-2的联合表达在肿瘤血管生成及成熟中的作用。方法:用常规免疫组织化学的方法检测41例口腔鳞癌及30例癌旁正常组织和10例正常口腔粘膜中的Ang-1及Ang-2的表达;通过双标免疫组织化学法同时检测CD34和α-平滑肌肌动蛋白,评估MVD及VMI。结果:口腔鳞癌组织与癌旁正常组织及正常口腔粘膜相比,Ang-2的表达显著增加(51.22%vs.26.67%,0%),而Ang-1的表达显著降低(41.46%vs.90.00%,90.00%),P值均<0.05;在癌旁正常组织与正常口腔粘膜之间,二者的表达没有显著性差异(P均>0.05)。对临床病理因素的分析发现,在高分化肿瘤中Ang-1的阳性率显著高于中分化肿瘤(56.00%vs.18.75%,P<0.05);而Ang-2的阳性率在有淋巴结转移的肿瘤显著高于无淋巴结转移肿瘤(84.62%vs.35.71%,P<0.01)。Ang-1和Ang-2的表达与肿瘤的血管生成及血管成熟密切相关(P值均<0.05)。联合Ang-1和Ang-2的表达发现,Ang-1与Ang-2相互拮抗共同调节肿瘤的血管成熟。结论:口腔鳞癌中Ang-1表达降低及Ang-2表达增高与肿瘤血管的生成及成熟密切相关。     

血管生成素-2/受体-2在乳腺癌中的表达及在血管新生中的可能作用

目的：检测乳腺癌组织中血管生成素2（Ang-2）及其受体Tie-2的表达水平,探讨二者在乳腺癌发生发展及血管生成中的调节作用。方法：采用免疫组化（SP法）对79例乳腺癌标本、68例癌旁组织及42例乳腺纤维腺瘤组织中Ang-2、Tie-2及CD34标记的微血管密度（MVD）进行检测,分析它们与乳腺癌血管生成的关系。结果：乳腺癌组织中Ang-2、Tie-2阳性率显著高于乳腺纤维腺瘤和癌旁正常组织中的阳性率（P〈0.05）,在Ⅲ期乳腺癌中的阳性表达率高于Ⅰ-Ⅱ期（P〈0.05）,在有腋窝淋巴结转移组中的阳性表达率高于无淋巴结转移组（P〈0.05）;Ang-2、Tie-2的表达与MVD均呈正相关（P〈0.05）。结论：Ang-2和Tie-2在乳腺癌血管生成和进展中可能起重要作用。