不同剂量塞来昔布对人肺癌裸鼠移植瘤的治疗作用及机制研究

目的:研究不同剂量COX-2抑制剂对人肺癌裸鼠移植瘤生长、survivin表达和微血管生成的影响.方法:将人肺癌A549细胞接种于裸鼠背部皮下建立移植瘤模型,然后随机分为4组:对照组、塞来昔布低剂量(25 mg·kg-1·d-1 )组、塞来昔布中剂量(50 mg·kg-1 ·d-1 )组、塞来昔布高剂量(100 mg·kg-1·d-1 )组.每周测量肿瘤体积,给药42 d后牺牲裸鼠,切取移植瘤组织,检测COX-2、 survivin 、VEGF表达和微血管密度(microvessel density,MVD).结果:塞来昔布低剂量组、中剂量组和高剂量组的抑瘤率分别为34.60%、49.40%和59.71%,与对照组比较,塞来昔布各治疗组肿瘤生长缓慢,差异有统计学意义( P <0.05).免疫组织化学染色和RT-PCR结果分析显示:与对照组比较,塞来昔布各治疗组COX-2 、survivin的表达水平均明显降低( P <0.05),并且抑制程度呈明显的药物剂量依赖性.低剂量塞来昔布可明显抑制VEGF mRNA表达和肺癌移植瘤微血管生成,其抑制作用并未随用药剂量的增加而增强.结论:不同剂量的塞来昔布均能明显抑制人肺癌裸鼠移植瘤的生长和survivin的表达,其抑制作用呈明显的用药剂量依赖性,survivin可能参与了塞来昔布抑制肺癌生成的过程.低剂量塞来昔布可抑制人肺癌裸鼠移植瘤微血管生成,可能对防止肿瘤转移起到重要作用.     

塞来昔布联合奥沙利铂对人肺癌裸鼠移植瘤的治疗作用及其作用机制的研究

目的：研究COX-2抑制剂与化疗药物奥沙利铂对人肺癌裸鼠移植瘤生长、Survivin表达和微血管生成的影响。方法：人肺癌A549细胞接种于裸鼠背部皮下,随机分为四组（对照组;奥沙利铂组;塞来昔布组;奥沙利铂和塞来昔布联合用药组）并给予相应的药物。测量肿瘤体积,42天后处死裸鼠,切取移植瘤组织检测COX-2,VEGF,Sur-vivin表达和微血管密度（MVD）。结果：塞来昔布组和奥沙利铂组抑瘤率分别为34.60%和46.70%,奥沙利铂和塞来昔布联合应用组抑瘤率为66.09%。免疫组织化学染色和RT-PCR结果分析显示：奥沙利铂组COX-2,VEGF表达显著高于对照组（P〈0.05）。微血管密度与对照组比较无显著性差异（P〉0.05）。奥沙利铂组Survivin表达低于对照组,塞来昔布组和联合用药组COX-2,VEGF表达和MVD低于对照组（P〈0.05）。结论：塞来昔布可抑制人肺癌裸鼠移植瘤的生长、Survivin表达和血管生成。塞来昔布与奥沙利铂联合应用提高了奥沙利铂的抗肿瘤效果。     

COX-2选择性抑制剂塞来昔布对裸鼠荷人子宫内膜腺癌的抑制作用

 目的 探讨环氧化酶-2（cyclooxygenase-2,COX-2）选择性抑制剂塞来昔布对人子宫内膜腺癌的治疗作用及其机制。 方法 建立人子宫内膜腺癌HEC-1B细胞裸鼠荷瘤模型,待成瘤后随机分为对照组与实验组,对照组予生理盐水口服2周,实验组分别予塞来昔布4mg/d和2mg/d口服2周。从治疗开始每3天计算瘤体积一次,描绘肿瘤生长曲线,治疗结束后处死裸鼠剥除瘤组织,计算抑瘤率,采用RT-PCR法测定移植瘤组织COX-2 mRNA的表达、免疫组化法测定COX-2蛋白的表达和微血管密度（MVD）。 结果 塞来昔布对裸鼠皮下移植瘤的生长具有明显的抑制作用,且随着药物浓度的增加,抑瘤作用逐渐增强（抑瘤率分别为 32.4％和48.6％）,RT-PCR结果显示移植瘤组织COX-2 mRNA的表达逐渐减弱,免疫组化结果显示移植瘤组织 COX 2蛋白的表达及微血管密度（MVD）逐渐减少,实验组与对照组之间及各实验组之间的差异均有统计学意义（P <0.05）,COX-2蛋白的表达与MVD数量呈正相关（r系数为0.921,P<0.01）。 结论 COX-2选择性抑制剂塞来昔布能够抑制裸鼠荷人子 宫内膜腺癌的生长,其机制可能与降低COX 2的表达、减少微血管的生成有关。     

VEGF-C和D2-40在结直肠癌组织中的表达及意义

目的:观察血管内皮生长因子-C(VEGF-C)和D2-40在结直肠癌中的表达,探讨淋巴管生成与淋巴道转移和临床病理特征的关系.方法:应用免疫组化SP法检测70例结直肠癌及20例正常结直肠组织中VEGF-C和D2-40的表达.结果:结直肠癌中VEGF-C表达率显著高于正常组织(P＜0.05).VEGF-C表达与患者淋巴结转移相关(P＜0.05).结直肠癌瘤周淋巴管密度(LDV-pt)显著高于瘤内淋巴管密度(LDV-it)和正常组织淋巴管密度(P＜0.05).瘤周淋巴管密度与VEGF-C表达和淋巴结转移密切相关(P＜0.05),而瘤内淋巴管密度与VEGF-C表达和淋巴结转移无关(P＞0.05).结论:VEGF-C可能在结直肠癌淋巴道转移过程中充当重要角色,结直肠癌瘤周淋巴管密度和VEGF-C表达水平可作为预测预后的有用指标.     

Ⅱ、Ⅲ期直肠癌组织中肿瘤淋巴管生成与COX-2和VEGF-C表达的关系

目的 探讨Ⅱ、Ⅲ期直肠癌组织中肿瘤淋巴管的生成与环氧化酶-2 (COX-2)和血管内皮生长因子-C (VEGF-C)表达的关系.方法 应用免疫组化方法测定肿瘤淋巴管密度(LVD)及Ⅱ、Ⅲ期直肠癌组织COX-2和VEGF-C的表达.结果 (1)直肠癌肿瘤旁LVD为15.3±5.8,显著高于直肠癌肿瘤周边区LVD(P<0.01),并且与淋巴结转移及预后相关;(2)直肠癌肿瘤旁LVD与VEGF-C、COX-2的表达不相关.结论 直肠癌肿瘤旁LVD与直肠癌的淋巴结转移和预后密切相关.     

结直肠癌组织VEGF-C和Podoplanin表达临床意义分析

目的:观察结直肠癌组织血管内皮生长因子-C(vascular endothelial growth factor-C,VEGF-C)和Podoplanin的表达,探讨VEGF-C和Podoplanin与结直肠肿瘤淋巴管生成、发生、发展及预后的关系。方法:收集2011-03-15-2012-03-15兰州军区兰州总医院肛肠外科手术切除的结直肠癌组织新鲜标本40例,同时收集距相应肿瘤组织边缘5～10cm的正常结直肠组织(以下简称正常组织)标本40例作为正常对照;应用免疫组织化学SP法检测40例结直肠癌组织及40正常结直肠组织VEGF-C和Podoplanin的表达,并采用t检验、单因素方差分析和χ2检验对两指标表达与临床病理因素之间相关性进行分析。结果:结直肠癌组织和正常组织VEGF-C阳性率分别为55%和15%,P=0.009。结直肠癌组织和正常组织VEGF-C Podoplanin阳性淋巴管密度(lymphatic vessel density,LVD)分别为6.03±3.72和3.33±2.76,P=0.001。结直肠癌组织中淋巴结转移组和无淋巴结转移组VEGF-C阳性率分别为94%和29%,P=0.034;且与pTNM分期和Dukes分期密切相关。结直肠癌组织淋巴结转移组和无淋巴结转移组中LVD值分别为8.11±3.46和4.82±3.31,P=0.004;且与pTNM分期和Dukes分期密切相关。结直肠癌组织VEGF-C阳性和阴性表达LVD值分别为7.73±3.34和3.78±3.40,差异有统计学意义,P=0.001。结论:结直肠癌中VEGF-C阳性率和Podoplanin阳性LVD显著增高,且与淋巴结转移、肿瘤病理分期密切相关,提示VEGF-C可能通过诱导结直肠癌淋巴管生成,从而促进肿瘤细胞的淋巴转移;证实VEGF-C和Podoplanin在结直肠肿瘤淋巴管生成、发生、发展及肿瘤转移中起重要作用,并可能成为肿瘤预后判断的参考指标。     

结直肠癌组织淋巴管密度和淋巴管内癌栓及VEGF-C表达的意义

目的:检测并比较结直肠癌及结直肠正常组织内淋巴管密度(LVD)和血管内皮生长因子(VEGF-C)的表达,并计数结直肠癌组织中淋巴管内癌栓(LVI),探讨其意义。方法:免疫组化法检测结直肠癌及相应的正常结直肠组织中LVD及VEGF-C的表达,计数结直肠癌组织LVI。结果:结直肠癌组织中的LVD明显高于正常结直肠组织,P=0.000。结直肠癌的LVD与LVI(P=0.001)及淋巴结转移(P=0.047)密切相关。LVI与TNM分期(P=0.017)及淋巴结转移(P=0.006)密切相关。结直肠癌组织中VEGF-C表达显著高于正常结直肠组织(P=0.000),且与肿瘤的TNM分期(P=0.029)及淋巴结转移(P=0.023)密切相关。结论:淋巴管的形成在结直肠癌的发生发展过程中起重要的作用。LVI及VEGF-C的表达可预测结直肠癌的侵袭性。     

塞来昔布联合氟尿嘧啶对MFC细胞615小鼠原位移植瘤COX-2、Fas表达的影响及意义

[目的]通过测定在塞来昔布及氟尿嘧啶干预下的小鼠前胃癌细胞(MFC)615小鼠原位移植瘤中环氧合酶(COX-2)、Fas的表达,对COX-2抑制剂联合氟尿嘧啶对胃癌的影响及意义进行探讨.[方法]制备MFC细胞615小鼠原位移植胃癌模型.造模成功后分为塞来昔布组、联合用药组及对照组,其中塞来昔布25mg/kg灌胃,氟尿嘧啶50mg/kg腹腔注射.观察各组小鼠一般情况.干预3周后处死小鼠,计算抑瘤率.SP免疫组织化学法检测各组肿瘤COX-2、Fas表达.[结果]造模成功率100.00％(30/30).联合用药组、塞来昔布组的小鼠一般情况优于对照组.实验结束后3组比较,塞来昔布组、联合用药组比对照组肿瘤体积和瘤重的抑制率均明显升高(P＜0.05).与塞来昔布组相比,联合用药组肿瘤体积更小、瘤重减轻(P＜0.05).COX-2蛋白在塞来昔布组、联合用药组表达阳性率明显低于对照组,而Fas蛋白的表达则明显高于对照组(P＜0.05).[结论]塞来昔布及氟尿嘧啶对胃癌有抑制作用,其机制与调节COX-2、Fas蛋白表达有关.     

塞来昔布联合顺铂对人舌鳞癌Tca8113细胞移植瘤的生长抑制作用

目的:通过动物实验观察COX-2抑制剂塞菜昔布与顺铂联合应用后对人舌鳞癌Tca8113细胞移植瘤的生长抑制作用.方法:将Tca8113细胞接种于裸鼠皮下,分别给予塞来昔布、顺铂及两者联合应用,35 d后处死裸鼠,测移植瘤质量,计算抑瘤率,光镜及电镜观察移植瘤组织学变化,免疫组化染色观察COX-2蛋白的表达,RT-PCR检测COX-2 mRNA表达.结果:COX-2抑制剂塞来昔布除抑制Tca8113细胞移植瘤生长及COX-2蛋白的表达外,还显著增强顺铂对移植瘤的生长抑制作用.塞来昔布组、顺铂组及塞来昔布+顺铂组的抑瘤率分别为15.63%、37.50%和82.81%,与对照组相比差异有统计学意义,P＜0.01;塞来昔布+顺铂组与塞来昔布及顺铂单独用药组相比,其抑制移植瘤生长差异有统计学意义,P＜0.01;塞来昔布对Tca8113细胞COX-2mRNA表达的抑制作用较弱,与对照组相比差异无统计学意义,P=0.073.结论:塞来昔布除了可以抑制裸鼠移植瘤生长外,还可以增强顺铂对Tca8113细胞裸鼠移植瘤生长抑制作用,其作用机制可能与抑制COX-2蛋白的表达有关,为进一步探索抑制COX-2酶的活性与防治头颈肿瘤的作用机制方面,提供了有益的参考.     

胃癌组织COX-2、VEGF-C表达与淋巴结转移及预后关系的研究

目的:探讨环氧化酶-2(cyclooxygenase-2,COX-2)、血管内皮生长因子C(VEGF-C)在胃癌组织中的表达及其与淋巴管生成、淋巴结转移及预后的关系.方法:采用免疫组织化学SABC法检测 51例胃癌及相应的癌旁组织COX-2、VEGF-C及受体VEGFR-3表达,计数肿瘤内淋巴管密度(LVD),并结合临床病理特征和随访资料进行分析.结果:胃癌组织COX-2、VEGF-C表达阳性率分别为62.8%(32/51),60.7%(31/51).COX-2表达与VEGF-C(r=O.74,P＜0.05)、临床分期(r=0.34,P＜0.05)、淋巴管密度(r=0.69,P＜0.01)和淋巴结转移(r=0.57,P＜0.01)呈正相关,与病理分化呈负相关(r=-0.58,P＜0.01).VEGF-C表达与淋巴管密度(r=0.45,P＜0.01)、淋巴结转移呈正相关(r=0.46,P＜0.05).随访5年,胃癌组织COX-2表达与生存率呈负相关,COX-2表达阴性组5年生存率(36.8%)显著高于COX-2表达阳性组(15.6%)(P＜0.05).结论:在胃癌组织中,COX-2、VEGF-C高表达,COX-2与VEGF-C、淋巴管密度、淋巴结转移呈正相关.推测COX-2通过诱导VEGF-C表达参与淋巴结转移.胃癌组织COX-2检测可能对推测预后具有重要意义.     

Cyclooxygenase-2 expression correlates with tumor neovascularization and prognosis in human colorectal carcinoma patients.

The role of cyclooxygenase-2 (COX-2) in tumor neovascularization of human colorectal carcinoma is yet to be delineated. One hundred colorectal carcinoma specimens were evaluated for COX-2 expression and CD34-stained microvessel density (MVD) by immunohistochemical methods. The relationships between COX-2 expression and clinicopathological feature of the patients, MVD, and survival time were analyzed. Increased COX-2 expression was significantly correlated with pathologically unfavorable findings such as tumor size (> 3.0 cm), tumor differentiation (poor, moderate > well differentiated), number of metastatic lymph nodes (24), and Dukes' stage (Dukes' B, C, and D). Larger number of microvessels congregated around the COX-2-expressing area, and the Spearman rank correlation test showed a strong correlation between COX-2 expression and tumor MVD (P < 0.0001). Patients with COX-2-positive tumors had a significantly (P = 0.037, by log-rank test) shorter survival time than those with negative tumors did. In the multivariate analysis, however, only Dukes' stage and number of metastatic lymph nodes remained as independent prognostic factors. Augmented tumor neovascularization may be one of the several effects of COX-2 responsible for poor prognosis in human colorectal carcinoma patients.     

VEGF-C 及VEGFR-3 在肝细胞癌中的表达

 目的　探讨VEGF-C、VEGFR-3、微血管密度（MVD）、微淋巴管密度（LVD）及肝细胞癌临床病理特征之间的关系。方法　取肝细胞癌组织标本60例，正常肝组织标本20例。采用反转录聚合酶链反应（RT-PCR）方法分析其中VEGF-C及VEGFR-3 mRNA 的表达，以免疫组织化学法检测肝癌MVD及LVD，并分析四者与肝癌临床病理特点之间的关系。结果　肝癌组织VEGF-C、VEGFR-3 mRNA表达、MVD及LVD高于正常肝组织（P＜0.01）；肝癌组织中，VEGF-C与VEGFR-3表达、MVD及LVD均呈正相关（P＜0.01），VEGF-C及VEGFR-3表达与肝癌肝内转移、门静脉癌栓形成及淋巴转移相关（P＜0.01），MVD与肝癌肝内转移、门静脉癌栓形成相关（P＜0.01），LVD与淋巴转移相关（P＜0.01）。结论　肝细胞癌组织中VEGF-C及VEGFR-3表达增多，可能通过参与血管、淋巴管生成促进肿瘤的侵袭、转移。     

CD105 、COX-2 和VEGF 在结直肠癌中的表达及其与血管新生的关系

 目的 探讨结直肠癌中CD105在新生血管中的表达，环氧化酶（COX-2）和血管内皮生长因子（VEGF）表达及其与血管生成的关系。方法 应用免疫组化SP法检测58例结直肠癌CD105表达的微血管密度，以及COX-2、VEGF的表达。结果 58例结直肠癌中，CD105表达的MVD值为（36．50±9．59），COX-2和VEGF的阳性表达率各为69％和67．2％。COX-2或VEGF表达阳性组的MVD值显著高于COX-2或VEGF表达阴性组（P〈0．05）。COX-2和VEGF均阳性组的MVD值显著高于均阴性组（P〈0．01）。COX-2与VEGF表达显著正相关；COX-2、VEGF表达均与MVD显著正相关（P〈0．01）。结论 CD105是结直肠癌新生血管的特异性标记物，COX-2表达与结直肠癌血管生成有关，VEGF可能是COX-2诱导血管生成的重要介质。     

环氧合酶-2在结直肠癌中的表达及其与微血管密度的关系

目的 检测结直肠癌组织中环氧合酶-2(COX-2)和微血管密度(MVD)的表达,并分析其临床意义.方法 应用免疫组织化学技术检测88例结直肠癌组织和20例正常结直肠黏膜中COX-2和MVD的表达.结果 与正常结直肠黏膜比较,结直肠癌组织中COX-2(3/20∶64/88)和CD34(7/20∶74/88)阳性表达率均增高(P均＜0.05).COX-2阳性表达的结直肠癌组织MVD(63.2±20.4)高于COX-2阴性者(41.2±29.8)(P＜0.01).结论 结直肠癌组织中COX-2呈高表达,且高表达的COX-2与肿瘤预后因素MVD相关.     

Coexpression of inducible nitric oxide synthase and COX-2 in hepatocellular carcinoma and surrounding liver: possible involvement of COX-2 in the angiogenesis of hepatitis C virus-positive cases.

Expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) has been reported to be responsible for enhanced tumor growth and angiogenesis in various tumors. However, the relationships between tumor vascularity and COX-2 and iNOS expression have not been evaluated in hepatocellular carcinoma (HCC). In this study, we examined the expression of iNOS and COX-2 and microvessel density (MVD) by immunohistochemical staining in 100 tissue sections collected from HCC patients. iNOS expression was significantly higher in hepatitis C virus (HCV)-positive HCCs (P = 0.011). COX-2 expression was significantly correlated with iNOS expression (P = 0.046) and tumor MVD (P = 0.011) in HCV-positive HCCS: iNOS expression was neither correlated with MVD nor had any influence on patient survival; however, combined negative expression of iNOS and COX-2 had a significant impact on patient survival (P = 0.041 and 0.018, log-rank test for overall and recurrence-free survival rate, respectively). The present findings suggest that combined expression of iNOS and COX-2 may play an important role in prognosis of HCV-positive HCC patients and that this could be partially attributable to modulation of angiogenesis by COX-2.     

Antitumor and anti-metastatic effects of cyclooxygenase-2 inhibition by celecoxib on human colorectal carcinoma xenografts in nude mouse rectum

We examined the effects of the preferential cyclooxygenase-2 (COX-2) inhibitor celecoxib on tumorigenesis, angiogenesis, apoptosis, vascular endothelial growth factor (VEGF) protein expression and metastasis in HT-29 human colorectal carcinoma cell xenografts in nude mouse rectum. COX-2 mRNA expression was examined in the xenograft and metastatic sites. The antitumor effect of celecoxib in the xenografts was evaluated by measuring the weight of the peri-ano-rectal tumor. The anti-metastatic effect of celecoxib was assessed by quantification of lymph node and lung metastases by amplification of a cancer-related human DNA by TaqMan PCR. The effects of celecoxib on angiogenesis, apoptosis, prostaglandin E2 (PGE2) production and VEGF protein expression in the xenografts were evaluated by means of microvessel density (MVD) counting, terminal deoxynucleotidyl transferase-mediated nick end labeling assay, quantitative enzyme-linked immunosorbent assay and western blotting, respectively. The rectal xenograft model showed lymph node and lung metastases with enhanced expression of COX-2 mRNA in each organ. Celecoxib inhibited rectal xenograft growth in a dose-dependent manner as follows: 150?ppm, 33.0% (p=0.000220); 750?ppm, 46.4% (p=0.0000292); 1500?ppm, 63.4% (p=0.0000109). Celecoxib inhibited lymph node metastasis in a dose-dependent manner as follows: 150?ppm, 86.7% (p=0.0263); 750?ppm, 90.3% (p=0.00638); 1500?ppm, 96.0% (p=0.000894). Celecoxib also inhibited lung metastasis as follows: 750?ppm, 53.3% (p=0.0107); 1500?ppm, 78.3% (p=0.00022). Celecoxib (1500?ppm) significantly inhibited PGE2 production by 68.4% (p=0.000157) and MVD counting by 48.2% (p=1.3x10-12) and induced apoptosis 2.5-fold (p=3.0x10-14) in the rectal xenograft. Celecoxib suppressed VEGF protein expression in the rectal xenograft. These studies demonstrate that celecoxib reduces the growth and metastatic potential of colorectal carcinoma in mice through COX-2 inhibition, anti-angiogenesis and apoptosis induction. The studies using HT-29 human colorectal carcinoma cell xenografts in nude mouse rectum also provide important information that supports that the COX-2 inhibitor celecoxib has a high potential for use as a clinical agent for inhibition of hematological and lymphatic metastases of colorectal cancer.     

Angiogenesis and Lymphangiogenesis in Salivary Gland Adenoid Cystic Carcinoma and Mucoepidermoid Carcinoma

Background and Purpose: This study aimed to investigate the immunohistochemical expression of CD31 and podoplanin in order to examine angiogenesis and lymphangiogenesis, respectively in common malignant tumors of salivary glands. Materials and Methods: Forty formalin-fixed, paraffinated blocks (20 adenoid cystic carcinoma and 20 mucoepidermoid carcinoma blocks) were selected from the medical archives of Amir A’lam Hospital of Tehran, Iran. Sections from the blocks were stained by CD31 and D2-40 markers via immunohistochemistry. Clinical and demographic information was extracted from the patients’ records. Findings: There was a significant difference between tumors in terms of intratumoral microvessel density (MVD) (P< 0.001), total MVD (P< 0.001), and intratumoral lymphatic vessel density (LVD) (P= 0.011). In mucoepidermoid carcinoma, intratumoral MVD and LVD were greater than peritumoral MVD and LVD (P= 0.001 and P< 0.001, respectively). In mucoepidermoid carcinoma, there was no relationship between histological grade with MVD (total, intratumoral or peritumoral) or LVD (total, intratumoral or peritumoral) (P> 0.05). A similar finding was reported with respect to the histopathological grade of adenoid cystic carcinoma (P> 0.05). Conclusion: The higher level of angiogenesis and lymphangiogenesis in mucoepidermoid carcinoma, specifically at the center of tumor, compared to adenoid cystic carcinoma, may be attributed to differences in the clinical behaviors and metastasis of tumors. Moreover, considering the high LVD at the center of tumor in mucoepidermoid carcinoma and infrequency of metastasis to regional lymph nodes in adenoid cystic carcinoma, it can play a significant role in metastasis to regional lymph nodes.     

环氧合酶-2 在子宫内膜癌中的表达及其与肿瘤血管形成的关系

 目的 探讨环氧合酶-2(Cyclooxygenase-2，COX2)在子宫内膜癌组织中表达及与肿瘤血管形成的关系。方法 采用免疫组化SIP方法检测34例子宫内膜癌组织COX-2和血管内皮生长因子(Vascu1arendothelial growth factor，VEGF)的表达和微血管密度(Microvessel density，MVD)，观察COX-2表达与肿瘤血管形成之间的相关性。结果 COX-2在子宫内膜癌组织中的阳性表达率为64．7％，而对照组正常子宫内膜均未见表达，内膜癌组的中分化细胞COX-2蛋白的表达高于低分化细胞，差异有显著性(P<0．05)；COX-2表达阳性组和阴性组MVD分别为(41．53±19．10和28．79±8．20)，两组比较具有显著性差异(P<0．05)。COX-2的表达评分与VEGF及MVD高度均呈正相关(P<0．01；P<0．0001)。结论 COX-2可能主要参与子宫内膜癌发生的早期；子宫内膜癌组织中COX-2的高表达可能在VEGF诱导肿瘤血管形成的过程中起重要作用。     

塞来昔布诱导人胃癌细胞凋亡抑制新生血管形成

目的 探讨环氧合酶2(COX-2)抑制剂塞来昔布对人胃癌细胞增殖和新生血管形成的抑制作用.方法 将59例胃癌患者随机分为试验组(37例)和对照组(22例),试验组术前给予常规剂量塞来昔布,共7d,然后行手术治疗;对照组行单纯手术治疗.免疫组化法检测胃癌组织中COX-2和血管内皮生长因子(VEGF)的表达及微血管密度(MVD),DNA末端原位标记染色法检测胃癌细胞凋亡.以20例健康人作为正常对照.结果 试验组胃癌细胞凋亡率为7.1%±1.0%,显著高于对照组(6.2%±0.9%,P<0.05).试验组和对照组中,COX-2阳性表达分别为16例(43.2%)和17例(77.3%),VEGF阳性表达分别为17例(45.9%)和16例(72.7%),差异均有统计学意义(P<0.05).试验组MVD为30.48±5.02,显著低于对照组(38.98±4.58,P<0.05).结论 塞来昔布可诱导人胃癌细胞凋亡,抑制胃癌新生血管形成.     

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.