Overexpression of cyclooxygenase-2 and tumor angiogenesis in human gastric cancer

BACKGROUND/AIMS: Cyclooxygenase-2 (COX-2) protein is overexpressed in various cancers, including esophageal, gastric, colon, and pancreatic. To better comprehend the role of COX-2 in gastric cancer, especially with regard to angiogenesis, we investigated COX-2 and vascular endothelial growth factor (VEGF) expression and microvessel density (MVD) in 108 patients with gastric cancer. METHODOLOGY: We used immunohistochemical analysis of formalin-fixed tissues of gastric cancer. RESULTS: Expression of COX-2 showed diffuse staining in the cytoplasm of tumor cells, however, no staining in normal epithelial cells. Of the 108 tumors examined, 71 (65%) were positive for COX-2 expression, the VEGF-positive cases numbered 43 of 108 cases (39.8%). The intensity of COX-2 expression did not correlate with any clinicopathological characteristics. The positive rate of VEGF expression in COX-2-positive cases was significantly higher than in COX-2-negative ones (47.9% vs. 24.3%, P<0.05). MVD in COX-2-positive cases was significantly higher than in COX-2-negative ones (22.0+/-7.8 vs. 18.5+/-7.5/1 mm2; P<0.05). CONCLUSIONS: Our study provides evidence that COX-2 is closely related with angiogenesis.     

Relationship between the expression of iNOS,VEGF,tumor angiogenesis and gastric cancer

AIM：To in vestigate the relationship between the expression of inducible nitric oxide synthase(iNOS),vascular endothelial growth factor(VEGF),the microvascular density(MVD)and the pathological features and clinical staging of gastric cancer.METHODS:Immunohistochemical staining was used for detecting the expression of iNOS and VEGFin46resected specimens of gastric carcinoma;the monoclonal antibody against CD34 was used for displaying vascular endothelial cells,and MVD was detected by counting of CD34-positive vascular endothelial cells.RESULTS:Of 46resected specimens of gastric carcinoma,the rates of expressions of iNOS and VEGF were 58.70%and76.09%,respectively,and MVDaveraged55.59&#177;19.39,Judged by the standard TNM criteria,the rate of expression of iNOS in stageⅣ（84.46%)was higher than those in stageⅠ,Ⅱ,Ⅲ（Fish exact probabilities test,P=0.019,0.023and 0.033,respectively);the rates of expression of VEGFin stage Ⅲ,Ⅳ（76.0%,92.31%,respectively)were higher than those in stageⅠ,Ⅱ（Fis exact probabilities test,P=0.031,0.017,0.022and0.019).MVDs in stageⅢ,Ⅳ（64.72&#177;14.96,67.09&#177;18.29,respectively)were higher than those in stageⅠ,Ⅱ(t\2.378,4.015,2.503and2.450,P&lt;0.05,P&lt;0.001,P&lt;0.001,P&lt;0.05,respectively),In37gastric carcinoma specimens with lymph node metastasis,MVD(68.69&#177;18.07)and the rates of expression of iNOS and VEGF(70.27%,83.78%,respectively)were higher than those in the specimens with absence of metastasis(t=2.205,X^2=6.3587,X^2=6.2584,P&lt;0.01,P&lt;0.05,P&lt;0.05,respectively),MVD and the expressions of iNOS and EGF were not correlated to the location,size or grade of tumor,nor with the depth of invasion of tumor;MVDs in the positive iNOS and VEGF specimens(59.88&#177;18.02,58.39&#177;17.73,repectively)were higher than those in the negative iNOS and VEGF specimens(X^2=6.3587and 6.1574,P&lt;0.05,P&lt;0.05,respectively);thus the expressions of iNOS and VEGF was correlated to MVD,but the expression of iNOS was not correlated to that of VEGF,In addition.of the 46 surviving patients,the 5-year survival rate of patients with positive iNOS or VEGF tumors was significantly less than that of patients with negative iNOS-or VEGF tumors(X^2=4.3842and 5.4073,P&lt;0.05,P&lt;0.05.respectively).CONCLUSION:The expressions of iNOS and VEGF are colosely related to tumor angiogenesis,and are involved in the advancement and the lymph node metastasis;thusMVD and the expressions of iNOS and EGF may serve indexes for evaluating staging of gastric carcinoma and forecasting its risk of metastasis,which will help establish a comprehensive therapeutical measure of post-operative patients and provide a new approach to tumor therapy.     

Relationship between inducible nitric oxide synthase expression and angiogenesis in primary gallbladder carcinoma tissue

AIM:To explore the relationship between angiogenesis and biological behaviors of primary gallbladder carcinoma (PGBC),the relationship between the expression of inducible nitric oxide synthase (iNOS) and biological behaviors of PGBC and its relationship with the expression of iNOS and angiogenesis of PGBC.METHODS: The expression of iNOS and micro-vessel density (MVD) were assessed by immunohistochemical method and image analysis system in 40 specimens of PGBC and in 8 specimens of normal gallbladder. The immunostaining results and related clinicopathologic materials were analyzed by statistical methods.RESULTS: MVD in PGBC was significantly higher than that in normal gallbladder tissue (46&#177;14 vs 14&#177;6, P&lt;0.05), and was not related with age, gender, tumor size and histological type. MVD of poorly and undifferentiated tumor tissues was higher than that of moderately-differentiated and well-differentiated tumor tissues (52&#177;9 vs43&#177;9 vs33&#177;6, P&lt;0.01).MVD of Nevin IV and V stages was higher than that of NevinI, Ⅱ and Ⅲ stages (52&#177;8 vs 37&#177;13, P&lt;0.01). MVD of cases with lymphatic or liver metastasis was significantly higher than that without liver metastasis (55&#177;6 vs 42&#177;10, P&lt;0.05) or lymphatic metastasis (53&#177;8 vs38&#177;8, P&lt;0.01). The positive level index (PLI) of iNOS in PGBC was 0.435&#177;0.134, and was not related with age, gender, tumor size, histological type,differentiation and clinical stage of PGBC. The PLI of iNOS in cases with lymphatic metastasis was higher than that without lymphatic metastasis (0.573&#177;0.078 vs 0.367&#177;0.064,P&lt;0.01). The PLI of iNOS in cases with liver metastasis was higher than that without liver metastasis (0.533&#177;0.067 vs0.424&#177;0.084, P&lt;0.05). There was a significant correlation between PLI of iNOS and MVD in PGBC (P&lt;0.05).CONCLUSION:Angiogenesis of PGBC is significantly related to the biological behaviors of PGBC. The expression of iNOS is related to the biological behaviors of PGBC. The detection of MVD and the expression of iNOS in PGBC can be used as parameters to determine the degree of malignancy and prognosis.     

Survivin、COX-2和VEGF在胃癌中的表达及其与预后的意义

目的研究生存素(Survivin)、环氧合酶-2(COX-2)和血管内皮生长因子(VEGF)在胃癌组织中的表达,探讨它们表达的关系及其与胃癌预后的关系。方法选取淮南东方医院集团总医院1992~2002年10年间行根治性手术治疗,临床、病理和随访资料齐全的胃癌患者65例,应用免疫组化S-P技术,检测Survivin、COX-2和VEGF在胃癌组织中表达。结果早期胃癌的5年生存率为95.2%(20/21),中期胃癌的5年生存率为63.6%(7/11)。中期胃癌组Survivin阳性表达高于早期胃癌组(73.6%vs 66.7%,P<0.05),其VEGF阳性表达和微血管密度(MVD)平均值高于早期胃癌组(P<0.05)。Survivin和COX-2在慢性萎缩性胃炎中的表达明显低于不典型增生者(P<0.05),在癌组织中的表达明显高于非癌组织(P<0.05)。胃癌组中的VEGF阳性表达率和MVD平均值均明显高于非癌组,且与胃癌浸润深度有关(P<0.05)。胃癌中Survivin、VEGF阳性表达的MVD值显著高于Survivin、VEGF阴性表达者(P<0.05);Survivin、COX-2、VEGF及MVD值与胃癌淋巴结转移、血管浸润均密切相关(P<0.05);Survivin、COX-2阳性表达及VEGF阳性表达者5年生存率明显低于阴性或低表达者(P<0.05)。多因素分析显示,淋巴结转移、浸润深度、Survivin表达、VEGF表达均为胃癌独立的预后因素。结论Survivin、COX-2、VEGF与胃癌的生长和浸润转移关系密切,可以作为反映胃癌生物学行为和判断预后的有效指标。     

COX-2 expression in gastric cancer and its relationship with angiogenesis using tissue microarray

AIM： To explore the expression and clinicopathological significance of cyclooxygenase-2 （COX-2） and microvessel density （MVD） in gastric carcinogenesis, and to investigate their roles in the invasion and the relationship between biological behaviors and prognosis of gastric cancer.
METHODS： Using Envision immunohistochemistry, COX-2 and CD34 expressions in gastric cancer tissue array were examined. MVD was counted and the relationship between the biological behaviors and prognosis was analyzed.
RESULTS： The expression of COX-2 in gastric cancer tissue was significantly higher than that in normal mucosa （χ^2 = 12.191, P 〈 0.05）. The over-expression of COX-2 in gastric cancer was obviously related to metastasis and depth of invasion （χ^2 = 6.315, P 〈 0.05）, but not related to the histological type and Borrmann type （χ^2 = 5.391 and χ^2= 2.228, respectively）. Moreover, MVD in gastric cancer tissues was significantly higher than that in the normal mucosa （65.49 ± 20.64 vs 36.21 ± 18.47, t/F = 7.53, P 〈 0. 05）. MVD was related to the histologic type and metastasis （t/F= 3.68 and t/F = 4.214, respectively, P 〈 0. 05）, but not related to the depth of invasion and Borrmann type （t/F = 0.583 and t/F = 0.459, respectively）. MVD in COX-2-positive tissues was markedly higher compared to COX-2-negative tissues, indicating a positive correlation between COX-2 expression and MVD （t = 13.12, P 〈 0. 05）.
CONCLUSION： Tissue microarray （TMA） is a powerful tool for rapid identification of the molecular alterations in gastric cancer. COX-2 expression, via inducingangiogenesis, may play an important role in gastric carcinogenesis. It could be served as a determinant factor for clinical prognosis and curative effect.     

Relationship between expression of CD105 and growth factors in malignant tumors of gastrointestinal tract and its significance

AIM: Angiogenesis is an important step in the growth of solid malignant tumors. A number of angiogenic factors have been found such as transforming growth factorβ1 (TGF-β1)and vascular endothelial growth factor (VEGF). However,the roles of TGFβ1 and VEGF in gastrointestinal carcinogenesis are still unclear. This study was to investigate the expressions of TGF-β1 and VEGF in gastrointestinal tract malignant tumors, as well as their association with microvessel density (MVD). At the same time, we also observed the localization of TGF-β1 and its receptor CD105 in gastric malignant tumors.METHODS: The expressions of TGF-β1 and CDL05 were detected in 55 fresh specimens of gastric carcinoma and VEGF and CD105 in 44 fresh specimens of colorectal carcinoma by immunohistochemical staining (S-ABC). TGF-β1 and CD105 in 55 gastric carcinoma tissues on the same slide were detected by using double-stain Tmmunohistochemistry (DS-ABC).RESULTS: Among the 55 cases of gastric carcinoma tissues,30 were positive for TGF-β1 (54.55 %). The MVD of TGF-β1 strong positive group (++～+++ 23.22±5.8) was significantly higher than that of weak positive group (+17.56±7.2) and negative group (- 17.46±3.9) (q=4.5, q=5.3207, respectively,P＜0.01). In the areas of high expression of TGF-β1, MVD and the expression of CD105 were also high. Among the 44 cases of colonic carcinoma tissues, 26 were positive for VEGF (59.1%). The expressions of both VEGF and CD105 (MVD)were related with the depth of invasion (F=5.438, P＜0.05;F=4.168, P=0.05), lymph node metastasis (F=10.311, P＜0.01;F=20.282, P＜0.01) and Dukes stage (F=6.196, P＜0.01;F=10.274, P＜0.01), but not with histological grade (F=0.487,P＞0.05). There was a significant correlation between the expression of VEGF and CD105 (MVD) (r=0.720, P＜0.01).CONCLUSION: Over-expression of TGF-β1 and VEGF acts as stimulating factors of angiogenesis in gastrointestinal tumors.CD105, as a receptor of TGF-β1, can regulate the biological effect of TGF-β1 in tumor angiogenesis. MVD marked by CD105 is more suitable for detecting newborn blood vessels.     

Inactivation of PTEN is associated with increased angiogenesis and VEGF overexpression in gastric cancer

AIM: To investigate the expression of PTEN/MMAC1/TEP1 and vascular endothelial growth factor (VEGF), their roles in biologic behavior and angiogenesis and their association in gastric cancer.METHODS: Immunohistochemical staining was used to evaluate the expression of PTEN, VEGF and microvascular density (MVD) on paraffin-embedded sections in 70 patients with primary gastric cancer and 24 patients with chronic superficial gastritis (CSG). Expression of PTEN, VEGF and MVD were compared with clinicopathological features of gastric cancer. The relationship between expression of PTEN, VEGF and MVD as well as the relationship between PTEN and VEGF expression in caner cells were investigated. RESULTS: PTEN expression significantly decreased (t= 3.98, P&lt;0.01) whereas both VEGF expression and MVD significant increased (t = 4.29 and 4.41, respectively, both P&lt;0.01) in gastric cancer group compared with CSG group. PTEN expression was significantly down-regulated (t=1.95, P&lt;0.05) whereas VEGF expression (t = 2.37, P&lt;0.05) and MVD (t= 3.28, P&lt;0.01) was significantly up-regulated in advanced gastric cancer compared with early-stage gastric cancer. PTEN expression in gastric cancer showed a negative association with lymph node metastasis (t= 3.91, P&lt;0.01), invasion depth (t= 1.95, P&lt;0.05) and age (t= 4.69, P&lt;0.01). MVD in PTEN-negative gastric cancer was significantly higher than that in PTEN-positive gastric cancer (t=3.69, P&lt;0.01), and there was a negative correlation betweenPTEN expression and MVD (γ=-0.363, P&lt;0.05). VEGF expression was positively associated with invasion depth (especially with serosa invasion, t = 4.69, P&lt;0.01), lymph node metastasis (t= 2.31, P&lt;0.05) and TNM stage (t= 3.04, P&lt;0.01). MVD in VEGF-positive gaslyic cancer was significantly higher than that in VEGF-negative gastric cancer (t=4.62, P&lt;0.01), and there was a positive correlation between VEGF expression of and MVD (y = 0.512, P&lt;0.05). VEGF expression in PTEN-negative gaslyic cancer was significantly stronger than that in PTEN-positive gastric cancer (t=2.61, P&lt;0.05), and there was a significantly negative correlation between the expression of VEGF and PTEN (γ=-0.403, P&lt;0.05).CONCLUSION: Our results imply that inactivation of PTEN gene and over-expression of VEGF contribute to the neovascularization and progression of gastric cancer. PTEN-related angiogenesis might be attributed to its up-regulation of VEGF expression. PTEN and VEGF could be used as the markers reflecting the biologic behaviors of tumor and viable targets in therapeutic approaches to inhibit angiogenesis of gastric cancers.     

Cyclooxygenase-2 overexpression correlates with vascular endothelial growth factor expression and tumor angiogenesis in gastric cancer

Angiogenesis is a key prerequisite for the successful establishment, growth, and dissemination of tumors. Vascular endothelial growth factor (VEGF) has a potent angiogenic activity and cyclooxygenase-2 (COX-2) promotes angiogenesis by modulated production of angiogenic factors including VEGF. The current study was designed to investigate the possible roles of COX-2 and VEGF in gastric cancer angiogenesis. In this study, we conducted an immunohistochemical investigation of COX-2 and VEGF expression in 97 patients with gastric cancer. To assess tumor angiogenesis, microvessel density (MVD) was determined by CD34 immunohistochemical staining. Expression of COX-2 and VEGF in gastric cancer tissues, was demonstrated in 63.9% and 75.3% of cases, respectively. The expression of COX-2 correlated significantly with VEGF expression. High MVD was significantly associated with depth of tumor invasion and poor survival. The mean MVD value of VEGF positive tumors was 79.8 +/- 32.0 and significantly higher than that of VEGF negative tumors. The mean MVD value of COX-2 positive tumors was 77.9 +/- 29.9 and not significantly higher than that of COX-2 negative tumor. The mean value of MVD in tumors positive for both COX-2 and VEGF was significantly higher than that in tumors negative for both. However, there was no correlation between COX-2 or VEGF expression and various clinicopathological features including patient survival. These results suggest that COX-2 may play an important role in carcinogenesis by stimulating tumor angiogenesis in concert with VEGF in human gastric cancer.     

Expression of COX-2 proteins in gastric mucosal lesions

AIM: To investigate the expression of COX-2 proteins in gastric mucosal lesions and to assess the relationship between COX-2 expression and type, pathologic stage, differentiation, or lymph node metastasis in gastric cancer and the relationship between COX-2 expression and H pylori infection in gastric mucosal lesions. METHODS: Thirty patients with gastric carcinoma underwent surgical resection. Samples were taken from tumor site and paracancerous tissues, and ABC immunohistochemical staining was used to detect the expression of COX-2 proteins. H pylori was determined by rapid urea test combined with pathological stating/14C urea breath test. RESULTS: The positive rate and staining intensity of mutant COX-2 gene expression in gastric cancer were significantly higher than those in paracancerous tissues (66.7% vs 26.7%) (P<0.01, P<0.001). There was a significant correlation between COX-2 and pathologic stage or lymph node metastasis type of gastric carcinoma (76.0% vs 20.0%, 79.2% vs 16.7%) (P<0.05). No correlation was found between COX-2 expression and type or grade of differentiation (P>0.05). COX-2 expression of intestinal metaplasia (IM) or dysplasia (DYS) with positive H pylori was significantly higher than that with negative H pylori (50.6% vs 18.1%, 60.0% vs 33.3%) (P<0.05). CONCLUSION: COX-2 overexpression was found in a large proportion of gastric cancer tissues compared with matched non-cancerous tissues and was significantly associated with advanced tumor stage and lymph node metastasis. Overexpression of COX-2 plays an important role in tumor progression of gastric cancer. COX-2 may also play a role in the early development/promotion of gastric carcinoma and is associated with H pylori infection.     

结肠癌COX-2mRNA表达与微血管密度关系的临床意义

目的通过观察结肠癌组织COX-2mRNA及CD34的表达，结合结肠癌组织中微血管密度（microvessel density，MVD）所见，探讨COX-2与肿瘤血管形成及病理特征的关系，为结肠癌生物治疗提供理论基础。方法 选择62例结肠癌、22例结肠腺瘤和22例正常结肠黏膜标本，采用原位分子杂交法检测COX-2mRNA并用MaxVisionTM快捷免疫组化法检测CD34表达，光镜下记数MVD。结果结肠癌、结肠腺瘤组织COX-2mRNA的阳性率明显高于正常黏膜，且有统计学意义（74．19％：36．36％，P=0．001；72．73％：36．36％，P=0．015）；结肠癌组平均MVD值高于腺瘤组和正常组，三组比较，有统计学意义（F=19．628，P=0．000）。在62例结肠癌组织中，高分化组COX-2mRNA阳性率高于低分化组（X^2=4．215、P=0．040）；进展期癌组的MVD高于早期癌组（t=3．079，P：0．003）；淋巴结有转移组MVD高于无转移组（t=3．180，P=0．002）；有血管侵犯组高于无血管侵犯组（t=2．093，P=0．041）；COX-2mRNA阳性组MVD高于阴性组，COX-2mRNA高表达组MVD高于低表达组，但差异均无统计学意义（P〉0．05）。结论MVD记数可作为判断肿瘤预后的有效评价指标，COX-2与肿瘤细胞的增殖和凋亡密切相关，与肿瘤血管生成无直接相关性。     

Tumor angiogenesis and its clinical significance in pediatric malignant liver tumor

AIM: To investigate the expression of vascular endothelial growth factor (VEGF) and microvascular density (MVD) count in pediatric malignant liver tumor and their clinical significances. METHODS: Fourteen children with malignant liver tumors including seven hepatocellular carcinomas (HCCs), five hepatoblastomas, one malignant mesenchymoma and one rhabdomyosarcoma were studied. Twelve adult HCC samples served as control group. All samples were examined with streptavidin-biotin peroxidase (SP) immunohistochemical staining for VEGF expression and MVD count. RESULTS: VEGF positive expression in all pediatric malignant liver tumors was significantly higher than that in adult HCC (0.4971±0.14 vs0.4027±0.03, P<0.05). VEGF expression in pediatric HCC group was also markedly higher than that in adult HCC group (0.5665±0.10 vs0.4027±0.03, P<0.01) and pediatric non-HCC group (0.5665±0.10 vs 0.4276±0.15, P<0.05). The mean value of MVD in pediatric malignant liver tumors was significantly higher than that in adult HCC (33.66±12.24 vs 26.52±4.38, P<0.05). Furthermore, MVD in pediatric HCC group was significantly higher compared to that in adult HCC group (36.94±9.28 vs 26.52±4.38, P<0.05), but there was no significant difference compared to the pediatric non-HCC group (36.94±9.28 vs 30.37±14.61, P>0.05). All 7 children in HCC group died within 2 years, whereas the prognosis in pediatric non-HCC group was better, in which two patients survived more than 5 years. CONCLUSION: Children with malignant liver tumors, especially with HCC, may have extensive angiogenesis that induces a rapid tumor growth and leads to a poor prognosis.     

Anti-cancer effects of COX-2 inhibitors and their correlation with angiogenesis and invasion in gastric cancer

AIM: To observe the anti-cancer effects of COX-2 inhibitors and investigate the relationship between COX-2 inhibitors and angiogenesis, infiltration or metastasis in SGC7901 cancer xenografts. METHODS: Thirty athymic mice xenograft models with human stomach cancer cell SGC7901 were established and divided randomly into 3 groups of 10 each. Sulindac, one non-specific COX inhibitor belonging to non-steroidal anti-inflammatory drugs (a series of COX inhibitors known as NSAIDs) and celecoxib, one selective COX-2 inhibitor (known as SCIs) were orally administered to mice of treatment groups. Immunohistochemistry was used to examine the expression of PCNA, CD44v6 and microvessel density (MVD). Apoptosis was detected by using TUNEL assay. RESULTS: Tumors in sulindac and celecoxib groups were significantly smaller than those in control group from the second week after drug administration (P<0.01). In treatment group, the cell proliferation index was lower (P<0.05) and apoptosis index was higher (P<0.05) than those in control groups. Compared with the controls, microvessel density was reduced (P<0.01) and expression of CD44v6 on tumor cells was weakened (P<0.05) in treatment groups. CONCLUSION: COX-2 inhibitors have anticancer effects on gastric cancer. They play important roles in angiogenesis and infiltration or metastasis of stomach carcinoma. The anticancer effects of COX-2 inhibitors may include inducing apoptosis, suppressing proliferation, reducing angiogenesis and weakening invasiveness.     

Role of inducible nitric oxide synthase expression in aberrant crypt foci－adenoma－carcinoma sequence

AIM: To investigate the expression of inducible nitric oxidesynthase (iNOS) in aberrant crypt foci (ACF) -adenomacarcinoma sequence and its relation with tumor cellapoptosis, proliferation and angiogenesis. METHODS: The expression of iNOS, proliferating cellnuclear antigen (PCNA) and microvessel density (MVD) indifferent stages of colorectal cancer were studied by immunohistochemical method from 30 normal tissues, 30nonhyperplastic ACF, 30 hyperplastic ACF, 30 dysplastic ACF,30 adenomas and 60 carcinomas. The apoptotic cells were detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method using an Apop Tag in situ detection kit. RESULTS: The immunoreactivity of iNOS significantly increased in the transition from hyperplastic ACF to dysplastic ACF. This transition was associated with a significant decrease in the apoptotic index (AI) (0.73+0.37 vs0.61±0.35, P＜0.05)and significant increases in the PCNA labeling index (LI)(27.3+2.80 vs 40.3+3.11, P＜0.01) and microvessel density (MVD) (55±11.5 vs 70±13.2, P＜0.01). The expression of iNOS was in low levels and positively correlated with PCNALI (r=0.812, P＜0.01) and MVD (r=0.863, P＜0.01) during transition from normal mucosa to nonhyperplastic ACF and hyperplastic ACF. The expression of iNOS was in high levels and positively correlated with AI (r=0.901, P＜0.01) after transition from hyperplastic ACF to dysplastic ACF, adenoma and carcinoma. CONCLUSION: The results suggest that the transition from hyperplastic ACF to dysplastic ACF may be a crucial step in the ACF-adenoma-carcinoma sequence, in which iNOS plays an important role by regulating tumor cell apoptosis,proliferation and angiogenesis.     

胃癌组织血小板衍化内皮细胞生长因子的表达与血管生成和凋亡的关系

目的探讨血小板衍化内皮细胞生长因子（PD．ECGF）在胃癌组织中的表达及与血管生成和凋亡的关系。方法应用免疫组化技术对67例胃癌组织进行PD－ECGF表达、肿瘤组织微血管密度（MVD）检测，流式细胞技术检测胃癌组织细胞凋亡指数（川，凋亡百分率八结果＊r＊＊＊F的表达与胃癌淋巴结转移（P＜0．oj）。分化程度（P＜0．05）及组织分型（P＜0．05）显著相关，与＊V则尸＜001）和胃癌细胞凋亡指数（P＜001）显著相关。＊＊D和＊1与淋巳结转移（P＜001）显著相关。结论胃癌组织中P＊。 ECGF可促进血管生成，抑制胃癌细胞凋亡，促进胃癌的增殖与转移。     

Prognostic significance of vascular endothelial growth factor expression and microvessel density in carcinoma of ampulla of Vater

BACKGROUND/AIMS: To investigate whether the expression of vascular endothelial growth factor (VEGF) and microvessel density (MVD) are of prognostic significance in ampullary carcinoma. METHODOLOGY: Twenty-two resected tumor specimens from patients with ampullary carcinoma were immunohistochemically stained for VEGF and CD34 (surrogate for vessels) by streptavidin-peroxidase method. RESULTS: Expression of VEGF in tumor tissue was found in 50% of patients. The mean MVD for entire group was 26.4 +/- 12.8. A significantly higher MVD was observed in the tumors with positive VEGF expression (35.0 +/- 9.6) compared with that of negative VEGF expression (17.7 +/- 9.3) (p<0.01). The expression of VEGF and MVD were closely related lymph node status and tumor TNM stage. The positive expression rate of VEGF and the average MVD in patients with lymph node metastases were 85.7% and 33.1 +/- 10.8 respectively, which were significantly higher than those in patients without lymph node metastases (33.3% and 22.8 +/- 11.8 respectively) (p<0.05). The positive expression rate of VEGF and the average MVD in patients with stage III and were 75% and 36.3 +/- 8.4 respectively, which were significantly higher than those in patients with stage I (25% and 18.4 +/- 10.1 respectively) or stage II (50% and 23.8 +/- 13.4 respectively) (p<0.05). The Kaplan-Meier survival curves showed that the 3-year survival rate for patients with positive VEGF expression or a high MVD (9.1% and 10% respectively) were lower than those in patients with negative VEGF expression or a low MVD (63.64% and 58.33% respectively) (p<0.05). CONCLUSIONS: VEGF is positively correlated with MVD in ampullary carcinoma. VEGF and angiogenesis may play an important role in lymph node metastasis and progression of ampullary carcinoma. VEGF and MVD appear to be important prognostic predictor in patients with ampullary carcinoma.     

Cyclooxygenase-2 promotes angiogenesis by increasing vascular endothelial growth factor and predicts prognosis in gallbladder carcinoma

AIM: To investigate the relationships between the expression of cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF) and the degree of vascularization, clinicopathologic feature, survival time of patients with gallbladder carcinomas. METHODS: Sixty-four gallbladder carcinoma specimens were evaluated for COX-2, VEGF expression by immunohi stochemical methods. Microvessel counts (MVC) were determined using CD34. The relationships between COX-2, VEGF expression, CD34-stained MVC, clinicopathologic features and survival time were analyzed. The correlations between COX-2 and VEGF expression, CD34-stained MVC were also investigated. RESULTS: COX-2, VEGF immunoreactivity were observed in 71.9% (46/64) and 54.7% (35/64) specimens, respectively. The average MVC in 64 cases of gallbladder carcinoma was 57±14 per high power vision field. The status of MVC was closely correlated with Nevin staging, tumor differentiation and lymph node metastasis (P<0.01, 0.002, and 0.003, 0.000, respectively). Increased VEGF expression was significantly correlated with tumor differentiation (poorly and moderately>well differentiated, P<0.05, P = 0.016). Clinical stages had no relation with the expression of VEGF (P>0.05, P = 0.612). There was a positive correlation between COX-2 expression and clinical stages. The positive rate of COX-2 was higher in cases of Nevin stages S4-S5 (81.8%) than in those of Nevin stages S1-S3 (50.0%) with a statistical significance (P0.01, P = 0.009). The expression of COX-2 did not vary with differentiation (P>0.05, P= 0.067). Statistically significant differences were also observed according to lymph node metastasis, COX-2 expression and VEGF expression (P<0.01,0.000, and 0.001, respectively). There was no relation between VEGF, COX-2 expression, MVC and the age and sex of patients. MVC and VEGF positive rate in the COX-2 positive gallbladder carcinoma tissue was higher than that in the COX-2 negative tissue (P<0.05, 0.000, and 0.032, respectively). Patients with VEGF, COX-2 positive tumors had a significantly shorter survival time than those with negative tumors (P<0.05,0.004, 0.01, respectively). CONCLUSION: Augmented tumor neovascularization induced by VEGF may be one of the several effects of COX-2 responsible for poor prognosis of human gallbladder carcinoma. COX-2 inhibitor, either in combination therapy with other agents, or for chemoprevention, may be effective via suppression of angiogenesis in this fatal disease.     

胃癌CT征象与癌组织中COX-2与p53的测定

[目的]探讨胃癌CT征象与胃癌组织中COX-2与p53表达之间的关系.[方法]48例胃癌患者术前行上腹部多层CT常规与增强扫描,记录CT观察指征,观察每个病灶的浆膜侵犯与淋巴结转移等情况.应用免疫组织化学SP法检测术后胃癌组织与正常胃黏膜中COX-2与p53的表达情况,并分析胃癌多层CT征象与COX-2、p53在胃癌组织中表达之间的关系.[结果]胃癌组织中COX-2与p53的阳性表达率高于正常胃黏膜组织（P＜o.01）,胃癌CT征象上肿瘤的浆膜侵犯与COX-2、p53表达有关（P＜0.05）,淋巴结转移与COX-2、p53表达有关（P＜0.01）,胃癌组织中COX-2与p53表达有相关性（P＜0.05）.[结论]胃癌组织中COX-2与p53的高表达与胃癌CT征象上的浆膜浸润与淋巴结转移有关,CT征象可以在一定程度上反映COX-2与p53的表达,胃癌组织中COX-2与p53表达具有一致性,两者在胃癌的发展中具有协同作用.