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1.
PURPOSE: The purpose of this study was to examine a variety of biomarkers in carcinoma of the cervix to better characterize (1). the natural history of the disease, (2). response to radiotherapy (RT), and (3). potential for new therapeutic strategies. MATERIALS AND METHODS: Fifty-five patients with Stage IB-IVA carcinoma of the cervix, treated with definitive intent RT, and on whom tumor tissue blocks were available were included in this study. Charts were reviewed for clinical parameters and disease status. Immunohistochemistry was performed for epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), CD34, topoisomerase II alpha (topo-II), and cyclooxygenase-2 (COX-2). Univariate and multivariate Cox proportional hazards modeling was performed with disease-free survival (DFS) and overall survival (OS) as the end points. Biomarkers were evaluated for correlation between various prognostic factors. RESULTS: In this series of 55 patients with carcinoma of the cervix treated with definitive RT, only stage was significant on univariate analysis for DFS (p < 0.0001). On univariate analysis, increasing FIGO stage (p < 0.0001) and membranous staining of EGFR (p < 0.037) indicated diminished OS. On multivariate analysis for DFS, COX-2, VEGF, and stage were significant (p = 0.012, p = 0.014, and p = 0.03, respectively), with increased expression indicating a worse prognosis. For OS, multivariate analysis revealed that VEGF, EGFR, and FIGO stage were significant (p = 0.005, p = 0.011, and p < 0.0001, respectively). Significant direct correlations were identified between VEGF and CD34 (p = 0.04), COX-2 and topo-II (p = 0.04), COX-2 and grade (p = 0.04), and tumor size and clinical stage (p = 0.04). CONCLUSION: Multivariate analysis revealed that increased staining for VEGF and COX-2 indicated diminished DFS, and VEGF and EGFR identified patients at increased risk of death. A significant direct correlation between VEGF and CD34 implicates the process of angiogenesis. Topo-II is a proliferative marker and it correlated directly with COX-2, indicating that expression of COX-2 may be greater in more proliferative tumors. Increased expression of EGFR, VEGF, and COX-2 has identified patients with a worse prognosis in cancer of the cervix. These data support the investigation of therapeutics that target these proteins in carcinoma of the cervix.  相似文献   

2.
目的研究环氧化酶-2(COX-2)、血管内皮生长因子(VEGF)在乳腺癌组织中的表达,并探讨其对血管生成的作用。方法应用免疫组织化学SP法检测30例乳腺癌组织标本和20例正常乳腺组织标本中COX-2、VEGF的表达,并用血管内皮细胞标记物CD34单克隆抗体标记行免疫组织化学染色,观察肿瘤微血管生成状况。结果COX-2在70.0%(21/30)乳腺癌组织中过表达,VEGF在56.7%(17/30)乳腺癌组织中过表达,与正常组织相比差异均有统计学意义;COX-2和VEGF表达相关;COX-2和VEGF表达均与肿瘤微血管生成相关。结论COX-2和VEGF过表达均与乳腺癌血管生成有关。  相似文献   

3.
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。  相似文献   

4.
Evidence indicates that cyclooxygenase (COX)-2-derived prostaglandins (PGs) contribute to tumor growth by inducing angiogenesis. We investigated the role of COX-2 in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). COX-2 and vascular endothelial growth factor (VEGF) expressions were examined by immunohistochemistry in 24 HBV-associated HCC. Tumor micro-vessel density (MVD) was assessed using CD34 immunohistochemistry. Hep3B HCC cell line, which carries integrated HBV genome, was stably transfected with human COX-2 cDNA. COX-2 and VEGF expressions were determined by Western blot while PG level was determined by ELISA. The effects of PGs on VEGF expression were also investigated. Expression of COX-2 and VEGF in HCC cells were observed in 19 (79%) and 16 (67%) cases, respectively. Well-differentiated HCC expressed COX-2 more strongly than less-differentiated HCC (p<0.001). COX-2 expression was found to correlate with VEGF expression and MVD (p=0.003 and 0.004, respectively). COX-2 overexpressing Hep3B clone had higher VEGF expression as compared to non-COX-2 expressing clone and parental cells. Treatment of the COX-2 overexpressing cells with a COX-2-selective inhibitor, NS-398 (10 microM), decreased PGE2 level and attenuated VEGF expression. Addition of PGE2 (10 microM) and the stable analog of PGI2, carbaprostacyclin (5 microM), to Hep3B cells also increased VEGF expression. Up-regulation of COX-2 correlates with VEGF expression and tumor angiogenesis in HBV-associated HCC. Moreover, COX-2 up-regulates VEGF expression in HCC cells, possibly via PGs production. Selective inhibition of COX-2 may block HCC associated angiogenesis and thus provides a rational approach for treatment of this malignancy.  相似文献   

5.
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.  相似文献   

6.
Although gastric cancer with cyclooxygenase (COX)-2 overexpression is associated with poor prognosis, the mechanistic pathway remains unknown. We examined the associations between expressions of COX-2 and vascular endothelial growth factor (VEGF) in both gastric cancer cells and in human gastric cancer. The gastric cell line, Kato III, was transiently transfected with cox-2 expressing vector. The levels of COX-2, prostaglandin (PG) E2 and VEGF expression were measured post-transfection. Additionally, expressions of COX-2 and VEGF in human gastric cancer were determined by immunohistochemistry in archive gastrectomy specimens. Tumor angiogenesis was assessed by the microvessel density (MVD), which was determined by anti-CD34 immunostaining. Transient transfection of Kato III with cox-2 was associated with increased COX-2 expression, higher PGE2 production and upregulated VEGF expressions. Treatment with NS398, a specific COX-2 inhibitor, reduced VEGF expression in COX-2 expressing Kato III cells by 25%. Among the 67 gastric cancers examined, COX-2 overexpression was found in 45 (67%) cases whereas increased VEGF expression was detected in 46 (69%) cases. There was a significant association between COX-2 and VEGF expressions in gastric cancer (r=0.25, p=0.041). Additionally, tumor MVD was associated with both COX-2 (r=0.32, p=0.008) and VEGF (r=0.39, p=0.001) expressions. Our results showed that overexpression of COX-2 in both gastric cells and primary gastric cancer is associated with upregulation of VEGF and angiogenesis. Future studies should evaluate the potential anti-angiogenic effect of COX-2 inhibitors on human gastric cancer.  相似文献   

7.
 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。  相似文献   

8.
 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。  相似文献   

9.
目的探讨环氧合酶-2(COX-2)和血管内皮生长因子(VEGF)与食管鳞癌患者放疗疗效和预后的关系。方法 60例食管鳞癌患者行局部放疗,并应用免疫组织化学方法检测放疗前组织COX-2和VEGF的表达情况,分析两者的表达与放疗疗效和预后的关系。结果 60例食管鳞癌患者中COX-2和VEGF的表达呈显著正相关。两者表达均阴性者放疗有效率较高,分别为94.7%和100.0%,且生存率亦高于阳性表达者。结论 COX-2和VEGF阳性表达的患者放疗疗效差,生存期短。两者联合检测可作为食管癌患者放疗后预后不良的指标。  相似文献   

10.
 目的 通过检测血管内皮细胞生长因子(VEGF)、基质金属蛋白酶-9(MMP -9)、环氧化酶-2(COX-2)在 甲状腺乳头状癌(PTC)细胞中的表达情况,探讨它们与PTC颈淋巴结转移的关系。 方法 采用免疫组织化学SP法检测74例PTC(有淋巴结转移者39例,无淋巴结转移者35例)中VEGF、 MMP-9、COX-2的表达,并对CD34表达阳性血管进行MVD计数。 结果 VEGF、MMP-9、COX-2的表达与MVD值在淋巴结转移组与无转移组之间的差异均具有统计学意义 (P<0.05),与PTC淋巴结转移呈正相关;VEGF、MMP-9、COX-2的表达与MVD值正相关 (P<0.05) ,VGEF、MMP-9阳性表达率与肿瘤大小密切相关(P<0.05)。 结论 甲状腺乳头状癌VEGF、MMP-9、COX-2蛋白表达与其淋巴道转移和MVD有关,检测这几种蛋白表 达将有助于判断甲状腺乳头状癌的转移潜能、血管生成能力及预后。  相似文献   

11.
目的:探讨血管内皮生长因子及其受体KDR在早期宫颈癌的表达及其对宫颈癌肿瘤血管生成的作用。方法:采用免疫组织化学SP法检测18例宫颈上皮内瘤样病变(cervicalintraepithelialneoplasm,CIN)、75例早期宫颈癌(invasivecarcinomaofcervix,ICC)和15例正常宫颈上皮(normalcervicalepithelium,NCE)中VEGF和KDR的表达情况,并检测其中微血管密度(CD34标记)。结果:在ICC中,VEGF和KDR主要表达于癌细胞膜和(或)细胞浆;而CD34主要表达于癌巢间质血管内皮细胞。从NCE到CIN再到ICC,VEGF与KDR的阳性表达率以及MVD均显著升高(P<0.01)。在ICC中,VEGF、KDR阳性表达者其MVD分别显著高于VEGF、KDR阴性表达者(P<0.05)。VEGF在ICC的表达与KDR显著正相关(r=0.56,P<0.01),并且两者均与MVD显著正相关(前者r=0.60,P<0.01;后者r=0.33,P<0.01)。VEGF与KDR均阳性表达者,其微血管密度显著高于两者均阴性表达者(P<0.01)。结论:VEGF及其受体KDR表达在宫颈癌肿瘤血管生成中起上调作用,两者均过度表达,肿瘤血管生成显著增加。检测VEGF及其受体KDR的联合表达对进一步了解宫颈癌血管生成情况以及寻找抗肿瘤血管生成治疗新靶点有一定价值。  相似文献   

12.
Wang J  Huang C  Wei XY  Zhan ZL  Sun H  Yang Y  Li K 《中华肿瘤杂志》2008,30(4):266-269
目的 探讨血管内皮抑制素对Calu-6裸鼠移植瘤生长及新生血管形成的影响.方法 在荷瘤裸鼠皮下注射不同剂量的血管内皮抑制素,观察注射后肿瘤体积的变化;应用免疫组化SABC法检测肿瘤组织中血管内皮生长因子(VEGF)、生存素(survivin)和环氧化酶-2(COX-2)蛋白的表达以及微血管密度(MVD)的变化;流式细胞术检测循环血管内皮细胞(CECs)的含量;应用逆转录聚合酶链反应(RT-PCR)和实时定量PCR检测外周血中CD146和CD105 mRNA的表达.结果经血管内皮抑制素治疗后,荷瘤鼠肿瘤体积明显减小;肿瘤组织中VEGF、survivin和COX-2蛋白的表达以及MVD均下降,且各治疗组与阳性对照组间的差异均有统计学意义(均P<0.05);外周血中CECs、CD146和CD105 mRNA的含量均明显下降;活化CECs的含量与肿瘤组织中survivin和VEGF的表达以及MVD的变化均呈正相关.结论 血管内皮抑制素可通过下调移植瘤中VEGF、survivin和COX.2蛋白的表达以及减少MVD抑制肿瘤生长;活化CECs将可能作为理想的预测抗血管形成治疗预后的标记物应用于临床.  相似文献   

13.
目的研究COX-2和VEGF在食管鳞癌中的表达及临床病理意义。方法应用免疫组化方法检测45例食管鳞癌和20例正常食管粘膜组织中COX-2、VEGF和CD34蛋白的表达。结果食管鳞癌中COX-2和VEGF的表达较正常食管组织明显增加。COX-2和VEGF阳性表达与肿瘤组织浸润深度、淋巴结转移及分期有关(P<0.05)。COX-2和VEGF的表达与MVD均相关。COX-2与VEGF的表达具有相关性。结论COX-2和VEGF在食管鳞癌中高表达,参与了食管癌的发生、浸润及转移,可以作为判断食管鳞癌生物学行为的指标之一。COX-2和VEGF在促进肿瘤血管生成调节机制中可能存在着协同效应关系。  相似文献   

14.
Prostaglandins(PGs) play a critical role in tumor development and growth by regulating numerous biologic processes, including tumor angiogenesis[1]. Cyclooxygenase-2 (COX-2) is an inducible enzyme that converts arachidonic acid to PGs. Overexpression of the COX-2 gene in mammary glands of transgenic mice was sufficient to induce tumorigenesis[2]. COX-2expression may contribute to the synthesis of PGs, which have been related to carcinogenesis and tumor progression. Recent studies have sh…  相似文献   

15.
Recent changes in the lifestyle of young women have led to an increase in the rate of uterine cervical cancer. We investigated the clinicopathological characteristics of uterine cervical cancer in young women, and examined the expression of vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMPs) and cyclooxygenase-2 (COX-2). Tumor samples from 439 patients with uterine cervical cancer, who were initially treated at Osaka City University Medical School Hospital, Japan between 1995 and 2004, were stained immunohistochemically. The patients were classified into two groups according to age at onset: group Y included women aged < or =35 years, and group O included women aged > or =36 years. Group Y had more cases of squamous cell carcinoma, while group O had more advanced cases (P<0.05). Advanced cases (beyond stage Ib2) had a significantly worse prognosis in group Y than in group O (P<0.05). There were no differences between the two groups in the expressions of VEGF, MMP-2 and COX-2. However, in advanced cases (beyond stage Ib2), the expression of VEGF, MMP-2 and COX-2 was significantly greater in group Y than in group O (P<0.05). The above findings suggest that the expression of VEGF, MMPs and COX-2 is related to a worse prognosis for advanced uterine cervical cancer in young women.  相似文献   

16.
环氧合酶-2对鼻咽癌血管生成及预后的影响   总被引:10,自引:0,他引:10  
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.  相似文献   

17.
OBJECTIVE: To evaluate the expressions of nuclear factor kappaB (NF-kappaB p65), inducible nitric oxide synthase enzyme (iNOS), and vascular endothelial growth factor (VEGF) in relation to angiogenesis (microvessel density, MVD) and clinical outcomes in adenoid cystic carcinoma (ACC) of salivary glands. METHODS: Immunohistochemical staining was used to quantify the protein expression levels of NF-kappaB p65, iNOS, and VEGF in 80 surgically resected ACCs and 20 normal salivary tissues. In all cases of ACCs, MVD was evaluated by counting CD34-reactive endothelial cells or endothelial cell clusters. RESULTS: The nuclear localization of NF-kappaB p65 was only detected in ACC cells. Both iNOS and VEGF staining activities in ACCs were more significant than those in normal gland tissues (P < 0.01). MVD had significant correlations with NF-kappaB p65, iNOS, and VEGF expressions (P < 0.01). In three histologic types of ACCs, the NF-kappaB, iNOS, VEGF expressions, and MVD were significantly higher in solid type than in cribriform and tubular types (P < 0.01). The NF-kappaB, iNOS, VEGF expressions, and MVD were significantly correlated with clinical stage, tumor size, vascular invasion, recurrence, and metastasis (P < 0.05). Multivariate analysis showed NF-kappaB, iNOS and VEGF expression, MVD, solid histotype, and perineural invasion had an independent prognostic effect on overall survival. CONCLUSION: The expressions of NF-kappaB p65, iNOS, and VEGF were related with MVD. Clinical outcomes raised the possibility that the overexpression of these cytokines might contribute to tumor angiogenesis and have prognostic value in ACCs.  相似文献   

18.
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。  相似文献   

19.
目的 探讨透明细胞性肾细胞癌(CCRCC)组织中环氧化酶2(COX-2)和血管内皮生长因子(VEGF)的表达及其与血管生成的关系.方法 应用免疫组化Envision法,检测80例CCRCC和20例正常.肾组织中COX-2和VEGF的表达及CD34标记的微血管密度(MVD),结合临床病理特征进行综合分析,探讨CCRCC组织中COX-2和VEGF的表达与血管生成的关系.结果 在CCRCC组织和正常肾组织中均有COX-2和VEGF表达.80例CCRCC中,COX-2和VEGF表达阳性率分别为65.0%和61.3%,均明显高于正常肾组织(分别为10.0%和20.0%).80例CCRCC组织MVD为70.13±19.99,20例止常肾组织MVD为59.75±15.17,差异有统计学意义(P<0.05).COX-2的表达与CCRCC组织学分级、TNM分期及淋巴结转移有关(P<0.05).CCRCC组织中,COX-2的表达与VEGF的表达呈正相关(r=0.485),COX-2和VEGF的表达均与MVD正相关(r分别为0.851和0.736).结论 COX-2与CCRCC血管生成有关,VEGF可能是COX-2调节CCRCC血管生成的重要中介.  相似文献   

20.
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.  相似文献   

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