COX-2、P53、MDR-1/P-gp在乳腺癌中的表达及其关系研究

目的探讨乳腺癌组织中环加氧化物酶-2(COX-2)、抑癌基因P53及多药耐药基因MDR-1/P-gp的表达及其相互关系。方法应用Envision免疫组织化学方法,半定量检测66例未经放、化疗的乳腺癌手术切除标本中COX-2、抑癌基因P53和MDR-1/P-gp的表达。结果 1.乳腺癌组织中COX-2、抑癌基因P53和MDR-1/P-gp的阳性表达率各为62.1%(41/66)、50%(33/66)和40.9%(27/66)。2.乳腺癌中COX-2的阳性表达与抑癌基因P53、多药耐药基因MDR-1/P-gp的阳性表达呈正相关(r分别为0.281和0.332,P<0.006)。3.抑癌基因P53的阳性表达与多药耐药基因MDR-1/P-gp的阳性表达呈正相关(r=0.277,P=0.024)。结论在乳腺癌组织中联合检测COX-2、P53和MDR-1/P-gp可以更好的指导临床乳腺癌的预后,可作为评估乳腺癌进展和判断预后的重要指标,寻找治疗乳腺癌新的作用靶点,同时对这些指标及其相关性的研究为其抑制剂在临床的应用或联合应用提供一定的分子学依据。

Expression of inducible nitric oxide synthase and cyclooxygenase-2 in pancreatic adenocarcinoma:Correlation with microvessel density

AIM:Cydooxygenases (COX) are key enzymes for conversion of arachidonic acid to prostaglandins.Nitric oxide synthase (NOS) is the enzyme responsible for formation of nitric oxide. Both have constitutive and inducible isoforms.The inducible isoforms (iNOS and COX-2) are of great interest as regulators of tumor angiogenesis,tumorigenesis and inflammatory processes.This study was to clarify their role in pancreatic adenocarcinomas. METHODS:We investigated the immunohistochemical iNOS and COX-2 expression in 40 pancreatic ductal adenocardnomas of different grade and stage.The results were compared with microvessel density and dinicopathological data. RESULTS:Twenty-one (52.5%) of the cases showed iNOS expression,15 (37.5%) of the cases were positive for COX-2. The immunoreaction was heterogeneously distributed within the tumors.Staining intensity was different between the tumors.No correlation between iNOS and COX-2 expression was seen.There was no relationship with microvessel density. However,iNOS positive tumors developed more often distant metastases and the more malignant tumors showed a higher COX-2 expression.There was no correlation with other clinicopathological data. CONCLUSION:Approximately half of the cases expressed iNOS and COX-2.These two enzymes do not seem to be the key step in angiogenesis or carcinogenesis of pancreatic adenocarcinomas.Due to a low prevalence of COX-2 expression,chemoprevention of pancreatic carcinomas by COX-2 inhibitors can only achieve a limited success.

Cyclooxygenase-2 expression after preoperative chemoradiotherapy correlates with more frequent esophageal cancer recurrence

AIM： To investigate the relationship between cycloo- xygenase-2 （COX-2）, and vascular endothelial growth factor （VEGF）, and to determine the clinical significance of this relationship in esophageal cancer patients undergoing chemoradiotherapy （CRT）. METHODS： Immunohistochemical staining was used to evaluate COX-2 and VEGF expression in 40 patients with histologically-confirmed esophageal squamous carcinoma （ESCC） who were undergoing preoperative CRT. RESULTS： Fourteen out of 40 ESCC patients showed a pathological complete response （CR） after CRT. COX-2 and VEGF protein expressions were observed in the cytoplasm of 17 and 13 tumors, respectively, with null expression in 9 and 13 tumors, respectively. COX-2 expression was strongly correlated with VEGF expression （P 〈 0.05）. There were also significant associations between COX-2 expression, tumor recurrence, and lymph-node involvement （P = 0.0277 and P = 0.0095, respectively）. COX-2 expression and VEGF expression had significant prognostic value for disease-free survival （log-rank test; P = 0.0073 and P = 0.0341, respectively）, but not for overall survival, as assessed by univariate analysis. expression correlates with VEGF expression and might be a useful prognostic factor for more frequent tumor recurrence in ESCC patients undergoing neoadjuvant CRT. These findings support the use of anti-angiogenic COX-2 inhibitors in the treatment of ESCC.