COX-2和p53蛋白在非小细胞肺癌中的表达及与微血管生成的相关性研究

目的探讨COX-2、p53的表达与肺癌血管生成及临床病理特征的关系。方法收集临床资料完整的肺癌手术标本85例,肺良性病变手术标本20例,采用免疫组化方法检测COX-2、p53蛋白及MVD的表达情况。结果(1)COX-2、p53在肺癌中阳性表达率分别为56.5%和58.8%,肺癌MVD值为43.55±11.45,均显著高于肺良性病变(P<0.05);(2)肺癌组织中COX-2表达与组织学类型、肿瘤分化程度和淋巴结转移显著相关(P<0.05);(3)肺癌组织中p53表达与淋巴结转移相关(P<0.05);(4)肺腺癌MVD值显著高于肺鳞癌,有淋巴结转移组MVD值显著高于无淋巴结转移组(P<0.05);(5)COX-2与MVD、p53与MVD、COX-2与p53的表达呈正相关。结论COX-2、p53的表达增强参与了肺癌的发生发展过程,两者在肺癌血管生成方面存在协同作用。联合检测两者的表达情况对肺癌的临床评价有重要价值,并可能成为肺癌治疗的新靶点。     

COX-2在非小细胞肺癌中的表达及与血管生成的关系

目的探讨COX-2蛋白在不同临床病理特征非小细胞肺癌(NSCLC)组织中的表达情况及其与肿瘤微血管密度(MVD)间的关系。方法采用免疫组化法的链霉菌抗生物素过氧化酶(S-P)法检测85例NSCLC组织和20例正常肺组织中COX-2、CD34表达情况。结果NSCLC组织中COX-2阳性表达率56.5%,显著高于肺良性病变组织中的阳性表达率5.0%(P<0.05);在腺癌组织中阳性表达率(75.0%)显著高于鳞癌组织中阳性表达率(40.0%)(P<0.05);在高、中、低分化鳞癌组织中阳性表达率分别为18.8%、35.7%、66.7%;在高、低分化腺癌组织中阳性表达率分别为58.8%、87.0%,差异均有统计学意义(P<0.05);在淋巴结转移组的肺癌组织中阳性表达率(70.0%)显著高于无淋巴结转移组中的阳性表达率(37.1%)(P<0.05);COX-2阳性组MVD值(50.44±9.09)显著高于COX-2阴性组MVD值(34.60±7.24)(P<0.05);经直线相关分析,两者呈正相关(r=0.876,P<0.01)。结论COX-2表达与肺癌分化程度密切相关,揭示了COX-2可以作为判断病情和评价预后的指标。COX-2表达与MVD呈正相关,推测其可能具有促进肿瘤血管生成的作用。     

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。     

CT增强时间密度曲线与肺癌血管生成关系的研究

背景与目的 新生血管形成与肿瘤细胞无限增殖密切相关.本研究的目的是分析肺癌组织中环氧化酶-2(COX-2)、血管内皮生长因子(VEGF)表达,微血管密度(MVD)与CT增强表现的相关性.方法 对经病理证实的25例肺癌及35例肺良性疾病患者行CT增强扫描,并应用PV法对病理标本进行免疫组化分析.结果 肺癌组COX-2(P＜0.05)、VEGF(P＜0.05)、MVD(P＜0.05)及CT强化峰值(P＜0.01)均明显高于肺良性肿瘤组.肺癌组织中COX-2、VEGF、MVD与组织学类型、临床分期、淋巴结转移及CT强化峰值之间有密切关系,与肺癌的分化程度无明显关系.结论 COX-2、VEGF、MVD可作为临床评价肿瘤发展、估计肿瘤预后的重要分子生物学指征.CT增强检查可以反映肺癌的血供特点,可根据CT增强峰值来推测肿瘤的侵袭、转移及预后情况.     

肺癌中的血管生成及其临床意义探讨

目的：研究VEGF、KDR的表达及微血管密度（MVD）在肺癌中的作用及其临床意义。方法：采有免疫组化方法（LSAB法）检测114例肺癌组织，癌旁组织、30例肺良性病变组织中的VEGF、KDR表达水平及MVD。结果：1）肺癌组织中VEGF、KDR表达水平显著高于肺癌旁组织和肺良性病变组织（P＜0．01），肺癌旁组织显著高于肺良性组织（P＜0．05）；肺癌组织中MVD显著高于肺良性病变组织（P＜0．01）。2）VEGF、KDR表达水平及MVD与肺癌原发肿瘤大小、淋巴结转移状态、P－TNM分期、细胞分化程度均有密切相关（P＜0．01）。3）VEGF在腺癌中表达最高，鳞癌次之，腺鳞癌最低。4）VEGF、KDR、MVD三者之间呈正相关（P＜0．01）。结论：VEGF、KDR及MVD参与肺吕的发生、发展、转移，可作为肺癌生物学行为恶化的一项评估指标。     

Ⅱ、Ⅲ期直肠癌组织中COX-2和VEGF-C的表达及其与肿瘤血管生成及预后的关系

背景与目的:Ⅱ、Ⅲ期直肠癌术后常发生血道转移,肿瘤新生血管生成是肿瘤血道转移的重要步骤,环氧合酶-2(COX-2)和血管内皮生长因子-C(VEGF-C)与肿瘤的新生血管生成有一定关系。本研究将探讨COX-2和VEGF-C在Ⅱ、Ⅲ期直肠癌组织中的表达及其与肿瘤生物学特征和肿瘤血管生成的关系。方法:免疫组化法检测Ⅱ、Ⅲ期直肠癌组织COX-2和VEGF-C的表达,并测定肿瘤微血管密度(MVD)。结果:①直肠癌组织中COX-2及VEGF-C高表达率均为72.5%,高于癌旁正常组织(9.8%和50.0%)(P均<0.05);直肠癌组织中MVD值为18.41±8.86,高于癌旁正常组织(11.24±7.4)(P<0.05);②COX-2在直肠癌组织中的表达与肿瘤组织的分化程度、浸润深度及VEGF-C的表达相关,与肿瘤的大小及淋巴结转移不相关;③VEGF-C在直肠癌组织中的表达仅与COX-2的表达相关,而与淋巴结转移、肿瘤组织的分化及浸润深度不相关;④在直肠癌组织中的MVD与肿瘤组织的分化程度、及VEGF-C、COX-2的表达相关,与肿瘤的大小、浸润深度及淋巴结转移不相关。结论:COX-2和VEGF-C的表达与Ⅱ、Ⅲ期直肠癌组织中肿瘤血管生成有密切关系,但与预后无关。     

胃癌组织中Survivin、COX-2蛋白表达及其与肿瘤血管生成的关系

目的:探讨Survivin,COX-2蛋白在胃癌组织中的表达及其与临床病理特征和肿瘤血管生成的关系.方法: 用免疫组化方法对65例胃癌组织Survivin,COX-2,CD34的表达进行检测.结果: 胃癌组织中Survivin蛋白阳性表达率为 70.77%(46/65),COX-2蛋白阳性表达率为76.93%(50/65).Survivin表达与分化程度和淋巴结转移有关(P<0.05),而与临床分期无关(P>0.05);COX-2的阳性表达与分化程度、临床分期和淋巴结转移有关(P<0.05).Survivin表达与COX-2的表达密切相关(r=0.235,P<0.05).Survivin阳性表达组织中 的MVD值为103.04±15.06,阴 性组为81.89±12.15,二者有显著差异(P<0.01).COX-2阳性表达胃癌组织中的MVD值为104.82±14.05,阴性组为81.02±13.73,二者有显著差异(P<0.01).结论: Survivin和COX-2对凋亡的抑制的协同作用及其促进血管生成的作用在胃癌的发生发展中起关键作用.     

COX-2、VEGF、Ki67在子宫内膜癌中的表达及意义

目的探讨环氧合酶-2(COX-2)、血管内皮生长因子(VEGF)和增殖细胞核相关抗原(Ki67)在子宫内膜癌发生、发展中的作用。方法采用免疫组织化学Envision法检测50例子宫内膜癌和15例正常子宫内膜组织中COX-2、VEGF、Ki67的表达。结果子宫内膜癌组织中COX-2、VEGF、Ki67的表达明显高于正常子宫内膜组织(P<0.01);COX-2的高表达与临床分期无关(P>0.05),与分化程度和浸润深度有关(P<0.01);VEGF的高表达与临床分期、浸润深度无关(P>0.05),分化程度有关(P<0.05);Ki67的高表达与临床分期(P<0.05)、分化程度、浸润深度有关(P<0.01)。COX-2与VEGF和Ki67的表达间存在正相关(r=0.39,P<0.01;r=0.32,P<0.05)。结论COX-2、VEGF、Ki67与子宫内膜癌的发生和发展相关,COX-2可通过使VEGF高表达,增加细胞增殖活性促进子宫内膜癌的发生、发展。     

肺癌患者血浆肾上腺髓质素与VEGF的相关性及其临床意义

目的 研究肾上腺髓质素(ADM)与血管内皮生长因子(VEGF)在肺癌患者中的表达、相关性及其临床意义,探讨ADM在肺癌中潜在的临床应用价值.方法 应用放射免疫分析法检测66例肺癌患者组、31例良性肺疾病组及16名健康者组血浆中ADM及VEGF表达水平.结果 ADM及VEGF血浆水平在肺癌组显著高于良性肺疾病组和健康组(P<0.05),ADM血浆水平在良性肺疾病组显著高于健康组(P<0.05),而VEGF血浆水平在良性肺疾病组与健康组差异无统计学意义(P>0.05);肺癌组远处转移者ADM及VEGF血浆水平显著高于局部淋巴结转移者(P<0.05),局部淋巴结转移者显著高于无淋巴结转移者(P<0.05).ADM及VEGF血浆水平与局部淋巴结转移、远处转移及TNM分期相关,而且随肿瘤分期增加ADM及VGEF血浆水平递增(P<0.05).肺癌组ADM与VEGF表达存在显著正相关(r=0.449,P<0.01).结论 ADM与VEGF在肺癌血管形成过程中具有协同作用;检测血浆ADM、VEGF血浆水平可能有助于肺癌与良性肺疾病的诊断及鉴别诊断,可能有助于肺癌临床分期;干预ADM及其信号传导通路可能成为肺癌靶向治疗的新途径.     

非小细胞肺癌组织ET-1、VEGF及MVD的表达及相互关系

目的:研究非小细胞肺癌(NSCLC)组织中内皮素-1(ET-1)、血管内皮生长因子(VEGF)的表达和微血管密度(MVD),以探讨ET-1、VEGF在肺癌组织血管形成中的调节作用.方法: 采用免疫组化和图像分析技术,检测40例NSCLC组织标本中ET-1 、VEGF的表达及MVD.结果: ET-1、VEGF在NSCLC组织表达率分别为55%(22/40)、62%(25/40),显著高于肺良性病变组8%(1/12)、0%(0/12)及正常对照组(0/10)、(0/10)(P<0.01);ET-1、VEGF表达阳性组MVD(26.23±3.52、23.40±5.29)显著高于ET-1、VEGF表达阴性组(15.46±4.85、16.40±3.85);ET-1、VEGF表达和MVD在低、中、高分化癌中存在显著差异[ ET-1(0.212±0.031 vs 0.147±0.015 vs 0.103±0.032)、VEGF(0.267±0.023 vs 0.166±0.021 vs 0.112±0.012)、 MVD(26.75±3.20 vs 23.14±3.38 vs 16.15±3.22)](P<0.01或P<0.05);淋巴结转移阳性组ET-1、VEGF表达和MVD值显著高于阴性组[ET-1(0.198±0.037 vs 0.141±0.032)、VEGF(0.256±0.022 vs 0.154±0.037)、MVD(27.62±3.58 vs 17.13±3.13)](P<0.01或P<0.05).结论: ET-1、VEGF调控肺癌组织血管形成,促进肿瘤的生长和转移.     

胃癌组织中COX-2和VEGF表达及其相关性研究

目的探讨环氧合酶2(cyclooxygenase-2,COX-2)和血管内皮生长因子(vascularendothelial growthfactor,VEGF)在人胃癌组织中表达及其相关性。方法应用免疫组织化学SABC法检测53例人胃癌组织中COX-2、VEGF和CD34的表达,并以40例正常胃粘膜标本作为对照。对CD34阳性血管进行微血管密度(microvesseldensity,MVD)计数。对COX-2和VEGF的表达采用半定量计分法判定,并结合临床资料进行统计学分析。结果53例人胃癌组织中,COX-2表达阳性者44例,阳性率为83.0%;VEGF表达阳性者45例,阳性率为84.9%。COX-2表达与VEGF表达相关显著(P<0.05)。并且,COX-2和VEGF的表达与TNM分期(P<0.05,P<0.05)、淋巴结转移(P<0.01,P<0.05)和远处转移(P<0.01,P<0.05)相关。COX-2/VEGF同高表达组中MVD值(79.5±25.8)高于COX-2/VEGF同低表达组中的MVD值(45.0±13.9),差异非常显著(P<0.01)。结论胃癌组织中COX-2与VEGF共表达,并相互协同促进肿瘤血管生成和转移。     

环氧合酶-2对鼻咽癌血管生成及预后的影响

目的研究环氧合酶-2(COX-2)在鼻咽癌中的表达及其对血管生成及预后的影响.方法选取临床资料完整并随访达5年以上的86例鼻咽癌患者,采用免疫组织化学技术检测活检标本中COX-2、血管内皮生长因子(VEGF)表达和微血管密度(MVD).结果 COX-2在鼻咽癌组织中阳性表达率为73.3%(63/86),与VEGF表达[69.8%(60/86)]呈显著正相关(rs=0.438,P<0.01),且与肿瘤分级、原发灶范围、颈淋巴结转移、远地转移及较短生存期亦具相关性.MVD平均数为32.3±12.8.结论 COX-2在鼻咽癌组织中高表达,与肿瘤血管生成密切相关,可作为预测鼻咽癌预后的一种有用指标.     

Correlation between cyclooxygenase-2 and tumor angiogenesis in non-small cell lung cancer

The role of COX-2 expression and angiogenesis of lung cancer is yet to be delineated. Eighty four non-small cell lung cancer (NSCLC) specimens were evaluated for COX-2 expression, microvessel density (MVD), and vascular endothelial growth factor (VEGF) expression by immunohistochemical methods. The relationships between COX-2 expression and MVD, VEGF expression, and survival time were analyzed. COX-2 expression was observed in the cytoplasm and membrane of the carcinoma cells, and premalignant cells. COX-2 was positive in 67 cases (79.8%). There was a statistically significant correlation between COX-2 expression and tumor size, TNM stage, tumor type, VEGF expression, and vascular pattern with survival in univariate analysis. No significant correlation was seen between COX-2, VEGF expression and MVD. A lack of expression of either COX-2 or VEGF expression or both, however, was associated with lower MVD than the group with both expressed. The difference was statistically significant (P=0.005). Statistically significant differences were also observed according to TNM stage, vascular pattern, COX-2 expression, and VEGF expression. With multivariate analysis, only TNM stage and COX-2 expression retained their significance as independent predictors of survival. COX-2 expression takes part in tumor angiogenesis and is a significant poor prognostic factor in the surgically resected NSCLC. COX-2 inhibitor, either in combination therapy with other agents, or for chemoprevention, may be effective via suppression of angiogenesis in this fatal disease.     

VEGF、p53、MMP-2在非小细胞肺癌的表达及与肿瘤血管形成和淋巴结转移关系的研究

 目的　研究VEGF、p5 3、MMP 2在非小细胞肺癌 (NSCLC)的表达及与肿瘤血管形成和淋巴结转移的关系。方法　用免疫组化S P法对 95例NSCLC组织VEGF、p5 3、MMP 2及肿瘤内微血管密度(IMVD)进行检测。结果　VEGF、p5 3、MMP 2阳性表达与IMVD和淋巴结转移等相关 (P <0 .0 5 )。 结论　VEGF、P5 3及MMP 2可能均参与了NSCLC的新血管生成并促进肿瘤转移 ,其检测可作为判断NSCLC转移及预后的指标。     

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.     

Total cyclooxygenase-2 mRNA levels correlate with vascular endothelial growth factor mRNA levels, tumor angiogenesis and prognosis in non-small cell lung cancer patients

Interaction between cancer cells and adjacent stromal cells is important to promote tumor development. Our aim was to study total COX-2 mRNA expression in both cancer cells and surrounding stromal cells and its association with angiogenic factor VEGF mRNA expression, tumor angiogenesis and prognosis in patients with NSCLC. COX-2 mRNA expression in both cancer cells and stromal tissue was analyzed using real-time quantitative (RTQ) RT-PCR in 60 NSCLC surgical specimens. Immunohistochemistry (IHC) was used to localize COX-2 protein in tumor specimens. Correlations between tumoral total COX-2 mRNA expression and VEGF mRNA expression (measured by RTQ RT-PCR), intratumoral microvessel counts (evaluated by IHC), other clinicopathologic variables, survival and relapse were tested. COX-2 protein expression was found in cancer as well as the surrounding stromal cells (including infiltrating inflammatory cells and endothelial cells of tumor-associated microvessels). VEGF protein expression was mainly located in cancer cells. There was a significant association between high tumoral total COX-2 mRNA expression and high VEGF mRNA expression (p = 0.01) or high intratumoral MVC (p < 0.001) but not other clinicopathologic variables, including tumor status and lymph node metastasis. Patients with higher tumoral total COX-2 mRNA expression had a statistically shorter survival time (median 15.0 +/- 2.61 months) and relapse time (median 5.0 +/- 1.37 months) than those with lower tumoral total COX-2 mRNA expression (median 40.0 +/- 3.12 and 34.0 +/- 3.11 months; p < 0.0001 and p < 0.0001, respectively, log-rank test). A significant difference in survival and relapse time was also seen between patients with high and low tumoral VEGF mRNA expression and between those with high and low intratumoral MVC (p = 0.0046 and p = 0.0038, respectively). After stratification by disease stage or histologic subtype, the prognostic significance of high total COX-2 mRNA expression was still apparent in both stage I and stage II-IV and in both squamous cell carcinoma and adenocarcinoma (p < or = 0.01 for all). Multivariate analysis using the Cox regression model with backward elimination showed that tumoral total COX-2 mRNA expression and lymph node status were the 2 most important independent prognostic predictors for survival and disease relapse. We report that total COX-2 mRNA expression in cancer cells and surrounding stromal cells correlates strongly and positively with VEGF mRNA expression, intratumoral MVC and adverse prognosis in NSCLC patients. This implies that COX-2 expression in both cancer cells and stromal cells within the tumor microenvironment may play an important role in upregulating the expression of the angiogenic factor VEGF and tumor angiogenesis in NSCLC and explains, in part, the adverse prognostic effect of COX-2 overexpression in patients with NSCLC.     

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.     

VEGF, b-FGF,NOS2 和 NOS3在非小细胞肺癌的表达及其临床意义

目的 :研究血管内皮生长因子 (VEGF)、碱性成纤维细胞生长因子 (b -FGF)、一氧化氮合酶 2 (诱生型 ,NOS2 )、一氧化氮合酶 3(内皮型 ,NOS3)在非小细胞肺癌 (NSCLC)中的表达及其与肿瘤血管形成和淋巴结转移的关系。方法 :用免疫组化 (S -P法 )染色技术对 95例NSCLC石腊组织标本的VEGF、b -FGF、NOS2 和NOS3及肿瘤内微血管密度 (IMVD)进行检测和分析。结果 :VEGF、b FGF表达与TNM分期、IMVD及淋巴结转移有关 (P<0 .0 5) ,两者共表达与IMVD有关 (P <0 .0 1 )。NOS3与组织学分型、IMVD和淋巴结转移有关 (P <0 .0 5) ;NOS2与IMVD有关 (P <0 .0 5)。相关分析显示促血管形成因子 (VEGF、b FGF)与一氧化氮合酶 (NOS2 、NOS3)的表达呈正相关 (r=0 .30 1 8,P <0 .0 5)。结论 :VEGF和b FGF在促进血管形成和促进肿瘤转移方面可能起到协同作用 ,并且有NO的参与 ;VEGF、b FGF、NOS2 和NOS3的检测对于判断NSCLC转移和预后及具有临床应用价值