利用组织芯片技术研究COX-2在胃癌中的表达及其与血管生成的关系

目的:研究COX-2在胃癌中的表达及其与血管生成的关系,探讨其在胃癌转移中的作用及与胃癌病理生物学行为的关系．方法:采EnVision方法检测胃癌组织芯片中 COX-2的表达,用CD34进行微血管内皮细胞染色,计算微血管密度(MVD),分析其相关性．结果:COX-2在胃癌中的表达明显高于正常胃黏膜(P=0．001)．COX-2的高表达与胃癌的转移(P=0．019)和胃壁浸润深度(0．031)呈正相关,与胃癌的组织病理分型无关(P=0．495), 与Borrmann分型无关(P=0．109)组织MVD (65．49±20．64)明显高于正常胃黏膜组织 (36．21±18．47,P=0．001)．MVD值与胃癌的组织病理分型(P=0．003)和转移有关(P=0．043), 与胃癌胃壁浸润深度(P=0．627)和Borrmann 分型(P=0．634)无明显相关性．COX-2表达阳性组的MVD指数明显高于COX-2表达阴性组 (68．59±19．8 vs 25．82±7．76．P<0．05),COX-2 表达与MVD呈正相关(P=0．001)．结论:组织芯片技术对于快速检测胃癌及其他肿瘤的分子病理学改变是一个强有力的工具．COX-2表达可能通过促进血管形成对胃癌的发生、发展起重要作用,其可作为判断预后和指导治疗的有效指标．     

食管癌组织芯片p53、p16和环氧合酶-2表达的研究

目的食管癌的发生发展是多步骤、多基因变化的演化过程，本研究利用高通量的组织芯片技术，对食管癌组织及癌旁组织的p53、p16和环氧合酶（COX）-2蛋白异常表达进行分析，探讨其相关性及临床意义。方法利用组织芯片技术结合免疫组化法检测86例食管癌组织、40例癌旁组织中p53、p16、COX-2蛋白的表达。结果食管癌组织中p53、COX-2的阳性表达率均显著高于癌旁组织（P〈0．05）。食管癌组织中p16阳性表达率为5．81％，癌旁组织中没有发现p16蛋白表达，差异无统计学意义。p53与p16、p53与COX-2、p16与COX-2蛋白表达均存在差异（P〈0.05）。p53或COX-2表达阳性时组织芯片病理类型为癌性的概率增加，但p16、p53和COX-2三者不存在交互作用。结论p53、COX-2对预测和早期诊断食管癌具有重要意义。     

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.     

Survey of molecular profiling during human colon cancer development and progression by immunohistochemical staining on tissue microarray

AIM： To explore the molecular events taking place during human colon cancer development and progression through high-throughput tissue microarray analysis. METHODS： We constructed two separate tissue microarrays containing 1.0 mm or 1.5 mm cylindrical samples acquired from 112 formalin-fixed and paraffinembedded blocks, including carcinomas （n = 85）, adenomatous polyps （n = 18）, as well as normal paracancerous colon tissues （n = 9）. Immunohistochemical staining was applied to the analysis of the consecutive tissue microarray sections with antibodies for 11 different proteins, including p53, p21, bcl-2, bax, cyclin D1, PTEN, p-Aktl, β-catenin, c-myc, nm23-h1 and Cox-2. RESULTS： The protein expressions of p53, bcl-2, bax, cyclin D1, β-catenin, c-myc, Cox-2 and nm23-h1 varied significantly among tissues from cancer, adenomatous polyps and normal colon mucosa （P = 0.003, P = 0.001, P = 0.000, P = 0.000, P = 0.034, P = 0.003, P = 0.002, and P = 0.007, respectively）. Chi-square analysis showed that the statistically significant variables were p53, p21, bax, β-catenin, c-myc, PTEN, p-Aktl, Cox-2 and nm23-h1 for histological grade （P = 0.005, P = 0.013, P = 0.044, P = 0.000, P = 0.000, P = 0.029, P = 0.000, P = 0.008, and P = 0.000, respectively）, β-catenin, comyc and p-Akt1 for lymph node metastasis （P = 0.011, P =0.005, and P = 0.032, respectively）, β-catenin, c-myc, Cox-2 and nm23-h1 for distance metastasis （P = 0.020, P = 0.000, P = 0.026, and P = 0.008, respectively）, and cyclin D1, β-catenin, c-myc, Cox-2 and nm23h1 for clinical stages （P = 0.038, P = 0.008, P = 0.000, P = 0.016, and P = 0.014, respectively）. CONCLUSION： Tissue microarray immunohistochemical staining enables high-throughput analysis of genetic alterations contributing to human colon cancer development and progression. Our results implicate the potential roles of p53, cyclin D1, bcl-2, bax, Cox-2, β-catenin and c-myc in development of human colon cancer and that of bcl-2, nm23-h1, PTEN and p-Akt1 in pro     

Comparative analysis of clinicopathological correlations of cyclooxygenase-2 expression in resectable pancreatic cancer

AIM:To perform a comparative analysis of clinicopathological correlations of cyclooxygenase2 (COX2) expression in pancreatic cancer, examined by monoclonal and polyclonal antibodies.METHODS: The COX2 expression in 85 resection specimens of pancreatic ductal adenocarcinoma was immunohistochemically examined using both monoclonal and polyclonal antibodies. The final immunoscores were obtained by multiplying the percentage of positive cells with the numeric score reflecting the staining intensity.COX2 expressi...     

Immunohistochemical analysis of cyclooxygenase-2 expression in pancreatic tumors

Summary Background A considerable amount of evidence collected from several experimental systems and clinical studies with nonsteroidal Anti-inflammatory drugs (NSAIDs) indicates that Cox-2 may play a major role in colorectal tumorigenesis, but little information about Cox-2 expression in pancreatic tumors is available. In this study, we investigated Cox-2 expression by means of both immunohistochemical analysis and immunoblot analysis in pancreatic tumors. Methods Fifty invasive ductal adenocarcinomas and 26 intraductal papillary-mucinous tumors (IPMTs) were used for immunohistochemical analysis, and five pancreatic cancer tissues and five pancreatic cancer cell lines for immunoblot analysis. Results Cox-2 was expressed in 72% of the invasive ductal adenocarcinomas, 31% of intraductal papillary-mucinous adenocarcinomas, and none of intraductal papillary-mucinous adenomas. The expression rate of Cox-2 in intraductal papillary-mucinous adenocarcinomas was significantly higher than that in intraductal papillary-mucinous adenomas, and that in invasive ductal adenocarcinomas was significantly higher than that in intraductal papillary-mucinous carcinomas. However, there was no significant correlation between Cox-2 expression and the prognosis and clinicopathological factors. Immunoblot analysis identified Cox-2 in all of pancreatic cancer tissues and 60% of cell lines. Conclusion The biological role of cyclooxygenase-2 (Cox-2) in carcinoma cells should be investigated with reference to the cancer progression of the pancreas.     

食管癌环氧化酶-2的高表达与淋巴转移的关系

目的　探讨环氧化酶 -2 (COX -2 )在食管癌中的表达情况及其与淋巴结转移的关系。方法　应用免疫组织化学方法(SP法 ) ,检测 1999～ 2 0 0 1年手术切除的 76例食管癌病人中COX -2的表达。其中有食管旁淋巴结转移者 18例 ,胃左动脉旁淋巴结转移者 11例。结果　COX -2在食管癌中的表达率为 81 6 %,主要为癌组织的表达 ,而在癌旁组织几乎不表达 ;食管癌旁和胃左动脉旁淋巴结转移组COX -2的表达水平均高于未转移组 (P <0 0 0 1)。结论　食管癌中COX -2的高度表达与食管癌的发生、发展及淋巴结转移有关 ,提示COX -2可能是防治食管癌的一个靶位。     

Identification of Annexin A1 protein expression in human gastric adenocarcinoma using proteomics and tissue microarray

AIM:To study the differential expression of Annexin A1(ANXA1)protein in human gastric adenocarcinoma.This study was also designed to analyze the relationship between ANXA1 expression and the clinicopathological parameters of gastric carcinoma.METHODS:Purified gastric adenocarcinoma cells(GAC)and normal gastric epithelial cells(NGEC)were obtained from 15 patients with gastric cancer by laser capture microdissection.All of the peptide specimens were labeled as18O/16O after trypsin digestion.Differential protein expressions were quantitatively identified between GAC and NGEC by nanoliter-reverse-phase liquid chromatography-mass/mass spectrometry(nanoRPLC-MS/MS).The expressions of ANXA1 in GAC and NGEC were verified by western blot analysis.The tissue microarray containing the expressed ANXA1 in 75 pairs of gastric carcinoma and paracarcinoma specimens was detected by immunohistochemistry(IHC).The relationship between ANXA1 expression and clinicopathological parametes of gastric carcinoma was analyzed.RESULTS:A total of 78 differential proteins were identified.Western blotting revealed that ANXA1 expression was significantly upregulated in GAC(2.17/1,P<0.01).IHC results showed the correlations between ANXA1protein expression and the clinicopathological parameters,including invasive depth(T stage),lymph node metastasis(N stage),distant metastasis(M stage)and tumour-lymph node metastasis stage(P<0.01).However,the correlations between ANXA1 protein expression and the remaining clinicopathological parameters,including sex,age,histological differentiation and the size of tumour were not found(P>0.05).CONCLUSION:The upregulated ANXA1 expression may be associated with carcinogenesis,progression,invasion and metastasis of GAC.This protein could be considered as a biomarker of clinical prognostic prediction and targeted therapy of GAC.     

脱氧胆酸调节环氧合酶-2对结肠癌细胞增殖的影响

目的 通过观察不同浓度脱氧胆酸对结肠腺癌细胞SW1116生长的效应，以及在相应状态下细胞内环氧合酶(COX)-2蛋白表达量的改变，探讨脱氧胆酸钠对结肠癌细胞的作用机制。方法 用MTT法测定细胞增殖活性；免疫组化及Western blot方法检测细胞内COX-2蛋白的表达。结果 10～100μmol／L的脱氧胆酸钠具有明显的促进结肠腺癌细胞生长的作用；大于100μmol／L时则表现出抑制作用。脱氧胆酸钠在10、50和100μmol／L的浓度下均可促进COX-2蛋白的表达，10μmol／L的效应可以持续72h，但后两者在48h后COX-2蛋白表达开始下降。结论 脱氧胆酸对结肠癌细胞SW1116增殖的影响呈双向调节作用，脱氧胆酸促进COX-2蛋白表达可能是其促进结肠癌细胞增殖的作用途径。     

胰腺癌环氧合酶-2表达的意义

目的研究胰腺癌中COX-2表达的意义．方法应用免疫组化SP法检测82例胰腺癌、22例慢性胰腺炎、9例胰腺良性肿瘤、15例正常胰腺组织和2株人胰腺癌细胞中COX-2的表达,然后比较胰腺癌组织COX-2表达与胰腺癌患者临床病理特征的关系。结果2株人胰腺癌细胞COX-2表达均阳性。70．7％（58／82）胰腺癌组织可见COX-2表达,而正常胰腺组织只有6．7％（1／15）呈微弱表达。COX-2在4种组织中的表达程度有显著性差异（P〈0．001）。胰腺癌组织COX-2表达显著高于其他3种组织（P〈0．05）。胰腺癌组织COX-2表达水平的高低与胰腺癌的临床病理特征无关（P〉0．05）。结论COX-2蛋白的检测对胰腺癌的诊断及其与胰腺良性肿瘤、慢性胰腺炎的鉴别诊断有帮助。胰腺癌组织COX-2表达不能作为预测患者预后的指标。     

Mechanism and clinical significance of cyclooxygenase-2 expression in gastric cancer

AIM: To determine the correlation between methylation status of 5' CpG island of cyclooxygenase-2 (COX-2) gene and protein expression in gastric cancer tissues for distinguishing the molecular characters of gastric cancers. METHODS: Methylation status of 5' CpG island of COX-2 gene was studied by PCR amplification after HpaⅡ and Hha I restrictive enzyme digestion;COX-2 expression was evaluated by immunohistochemical method. RESULTS: Hpa Ⅱ and HhaI site were all methylated in 12 normal gastric mucosa tissues, whereas they were demethylated in 77.27% (34/44) and 84.09% (37/44) gastric cancer tissues,respectively.Expression of COX-2 was detected in 68.18% (30/44) gastric cancer tissues, but no expression was found in normal gastric mucosa tissues. In gastric cancer tissues, COX-2 expression was correlated significantly with HpaⅡ site demethylation (29/30 vs 5/14, P<0.001 and HhaI site demethylation (28/30 vs 9/14,P<0.05). CONCLUSION: The demethylation of 5' CpG island of gene is necessary for COX-2 expression in human gastric cancer. The expression status of COX-2 may provide theoretical basis for COX-2 targeting gastric cancer treatments.     

Expression of p53, p16 and cyclooxygenase-2 in esophageal cancer with tissue microarray

OBJECTIVE: The aim of this study was to obtain a comprehensive survey on the expression of p53, p16 and cyclooxygenase‐2 (COX‐2) in esophageal cancer progression and their clinical significance. METHODS: A tissue microarray containing 86 specimens from esophageal cancer and 40 specimens from adjacent non‐cancer tissue was constructed to survey the expression of p53, p16 and COX‐2 by immunohistochemistry. The influence of each biomarker on the histotype of esophageal lesion was assessed by logistic regression analysis. RESULTS: The expression of p53 and COX‐2 was significantly higher in tumorous tissue than in non‐tumorous tissue. As to p16, no significant difference was detected between tumorous and non‐tumorous tissue. A significant correlation was observed among p53, COX‐2 and p16 expression. Logistic regression analysis revealed that the risk factors of a tumorous histotype were the positive expression of p53 (odds ratio [OR] = 18.214) or COX‐2 (OR = 42.703), and no reciprocal relationship to neoplastic progression was recognized with p53, p16 and COX‐2. CONCLUSIONS: p53 and COX‐2 were independent predictors in esophageal carcinogenesis. Esophageal tissue with a positive expression of p53 or COX‐2 was more likely to develop esophageal cancer.     

HER2 in gastric cancer: Comparative analysis of three different antibodies using whole-tissue sections and tissue microarrays

AIM:To compare the performance of three commercially available anti-human epidermalgrowth factor receptor 2(HER2)antibodies in whole-tissue sections and tissue microarrays(TMAs)of a series of gastric tumors.METHODS:We present a comparative analysis of three anti-HER2 antibodies(HercepTest,4B5 and SP3)using TMA and whole-tissue sections prepared from the same paraffin blocks of 199 gastric adenocarcinomas operated upon between January 2004 and December2008 at a Brazilian cancer hospital.The data on the patients’age,sex,the anatomical location of the tumor and the Lauren’s histological classification were collected from clinical and pathological records.The immunohistochemical(IHC)results were examined by two pathologists and the cases were classified as positive(3+),equivocal(2+)and negative(0 or 1+),according to the criteria of the IHC scoring system of gastric cancer.TMAs and whole-tissue sections were evaluated separately and independently.All cases yielding discordant IHC results and/or scored as 2+were subjected to dual-color in situ hybridization in order to determine the final HER2 status.Besides determining the sensitivity and predictive value for HER2-positive status,we measured the accuracy of each antibody by calculating the area under the receiver operating characteristic(ROC)curve.The agreement between the results obtained using the TMAs and those obtained using the whole-tissue sections was assessed by means of Kappa coefficient.RESULTS:Intratumoral heterogeneity of HER2 expression was observed with all antibodies.HER2-positive expression(3+)in the whole-tissue sections was observed in 23 cases(11.6%)using the 4B5 antibody,in 18 cases(9.1%)using the SP3 antibody and in 10 cases(5.1%)using the HercepTest antibody.In the TMAs,11 positive cases(5.6%)were identified using SP3 antibody,9(4.6%)using the 4B5 antibody and 6(3%)using the HercepTest antibody.The sensitivity using whole-tissue sections and TMA,respectively,was 95.2%and 42.9%with 4B5,90.5%and 66.7%with SP3 and 47.6%and42.9%with HercepTest.T     

利用组织芯片技术研究P73和mP53基因编码蛋白在胃癌中的表达及意义

目的:构建胃癌及其癌前病变组织芯片,采用免疫组化方法观察研究P73和mP53基因编码蛋白在胃癌中的表达并探讨其临床病理学意义.方法:收集2003-2004年辽宁省肿瘤医院和中国医大附属一院104例胃癌及癌前病变组织标本构建两个组织芯片蜡块,组织样品直径为1 mm.采用SABC免疫组化方法检测胃癌组织中P73和mP53蛋白的表达,观察分析其与胃癌病理生物学行为的关系.结果:P73基因编码蛋白在胃癌、肠上皮化生、不典型增生病变组织中的阳性表达率显著高于远癌正常胃黏膜(90.1%,44.0%,80.0%vs 17.9%,P＜0.01).Borrman Ⅲ/Ⅳ型胃癌P73蛋白阳性表达率(92.9%/100%)显著高于BorrmanⅡ型胃癌(57.1%)(P＜0.05).伴转移胃癌组P73蛋白阳性表达率(淋巴结转移组94.4%,肝转移组100%,卵巢转移100%)显著高于无转移组(76.2%)(P＜0.05).胃癌组织中P73蛋白表达与mP53蛋白表达密切相关(χ2=9.6736,P＜0.01).结论:P73蛋白表达与胃癌恶性病理生物学行为密切相关,其虽与抑癌基因P53同源,但与mP53蛋白表达呈正相关,提示其可能作为P53的一种模拟突变体在胃癌发生、发展中起作用.     

环氧合酶—2在胰腺癌中的表达及其临床意义

目的 探讨胰腺癌中COX-2的表达及其临床意义、方法 应用免疫组化SP法检测45例胰腺癌、11例慢性胰腺炎、7例胰腺良性肿瘤和10例正常胰腺组织中COX-2的表达。结果 正常胰腺和慢性胰腺炎组织的导管上皮和腺泡细胞未见COX-2的表达,7例良性胰腺肿瘤有2例COX-2呈阳性表达,45例胰腺癌中,有34例COX-2呈阳性表达,阳性率为75.6％。COX-2在胰腺癌中的表达显著高于正常胰腺、慢性胰腺炎和胰腺良性肿瘤(X_2分别为19.79、21.16和6.28,P<0.0001、P0.05)。结论 COX-2的过度表达在胰腺癌的发生中可能具有重要作用,COX-2抑制剂对胰腺癌的预防和治疗可能有效。     

Immunoexpression of cyclooxygenase-2 in primary gastric carcinomas and lymph node metastases

AIM: To evaluate immunoexpression of cyclooxygenase-2 (COX-2) in primary gastric carcinomas and respective lymph node metastases.METHODS: Immunohistochemistry to analyze COX-2 expression was performed on tissue microarray slices obtained from 36 specimens of gastrectomy and satellite lymph nodes from patients with gastric carcinoma.RESULTS: Immunostaining was seen in most cases, and COX-2 expression was higher in lymph node metastases than in corresponding primary gastric tumors of intestinal, diffuse and mixed carcinomas, with a statistically significant difference in the diffuse histotype (P = 0.0108).CONCLUSION: COX-2 immunoexpression occurs frequently in primary gastric carcinomas, but higher expression of this enzyme is observed in lymph node metastases of the diffuse histotype.     

Correlation of bFGF expression in renal cell cancer with clinical and histopathological features by tissue microarray analysis and measurement of serum levels

The prognostic value of bFGF for surgically treated renal cell cancer (RCC) patients was evaluated by immunohistochemistry (IHC) and the tissue microarray technique (TMA). Additionally, preoperative serum bFGF levels were correlated to tumour stage and the presence of metastases at initial diagnosis. Serum levels of bFGF were measured by ELISA in 39 healthy volunteers, in 37 patients with benign urologic diseases and in 74 RCC patients, 26 of whom revealed lymph node or distant metastases. bFGF expression as detected by IHC was investigated in 777 tissue cores from 259 different RCC patients [median follow-up: 138 (36–240) months]. Eighty eight patients died from tumour progression. For each patient, the TMA slides contained a tissue core from the primary tumour, its invasion front and the normal renal parenchyma. bFGF serum levels were higher in RCC patients vs healthy volunteers (P<0.01) and vs patients with benign urologic diseases (P<0.01). Metastasized patients revealed higher bFGF serum levels than organ-confined specimens (P<0.01). As detected by IHC only increased bFGF expression in the invasion front tissue correlated with the patients’ long-term survival (log rank test) (P=0.03). In multivariate analysis regional LN metastases (P<0.01), the histological grading (P<0.01), and an increased bFGF expression in the invasion front (P=0.04) independently predicted the patients’ clinical prognosis. Not the expression of bFGF in the primary tumour but in its invasion front reflects the aggressiveness of RCC, hereby indicating a different biological potential within both areas. The value of bFGF serum levels as indicators of systemic tumour dissemination remains to be determined.     

Expression of cyclooxygenase-2 in colorectal cancer and its clinical significance

AIM: To clarify the clinicopathologic significance of COX-2 expression in human colorectal cancer. METHODS: A total of 128 surgically resected colorectal cancer specimens were immunohistochemically analyzed with the use of anti-COX-2, anti-VEGF and anti-MMP-2 antibodies. The relationship between the cyclooxygenase-2 expression in primary lesions of colorectal cancer and clinicopathoiogic parameters was evaluated by chi-square test. RESULTS: Among 128 cases of colorectal cancer, 87 (67.9%) were positive for cyclooxygenase-2. The expression of cyclooxygenase-2 was significantly correlated with the depth of invasion, stage of disease, and metastasis (lymph node and liver). Patients in T3-T4, stages Ⅲ-Ⅳand with metastasis had much higher expression of cyclooxygenase-2 than ones in T1-T2, stages Ⅰ-Ⅱ and without metastasis (P<0.05). Among 45 cases of colorectal cancer with lymph node metastasis, the COX-2-positive rate was 86.7% (39/45) for primary lesions and diffuse cytoplasmic staining for COX-2 protein was detected in cancer cells in 100% of metastatic lesions of the lymph nodes. VEGF expression was detected in 49 tumors (38.3%), and VEGF expression was closely correlated with COX-2 expression. The positive expression rate of VEGF (81.6%) in the cyclooxygenase-2-positive group was higher than that in the cyclooxygenase-2-negative group (18.4%, P<0.05). MMP-2 expression was detected in 88 tumors (68.8%), and MMP-2 expression was closely correlated with COX-2 expression. The positive expression rate of MMP-2 (79.6%) in the positive COX-2 group was higher than that in the negative COX-2 group (20.4%, P<0.05). CONCLUSION: Cyclooxygenase-2 may be associated with tumor progression by modulating the angiogenesis and cancer cell motility and invasive potential in colorectal cancer and it can be used as a possible biomarker.     

环氧合酶-2在胰腺癌治疗中的作用

在众多实体瘤中,胰腺癌的预后最差,炎症是其发展过程中的重要影响因素。环氧合酶-2（COX-2）在大多数胰腺癌中高表达并调控其发生发展过程。COX-2在肿瘤细胞生成、凋亡、血管生成方面有着重要作用,因此它是治疗胰腺癌极好的分子靶点。大量的实验证明阻滞COX-2的表达对治疗胰腺癌有良好的效果,治疗方法主要包括COX-2抑制剂、基因治疗、抗氧化剂、生长因子受体抑制剂、生物碱等。本综述主要讨论各种治疗方法的应用和不足,总结COX-2在胰腺癌治疗中的作用。     

诱导型一氧化氮合酶、环氧合酶-2与乳腺癌淋巴管生成的关系及其临床意义

目的探讨诱导型一氧化氮合酶(iNOS)和环氧合酶-2(COX-2)在乳腺癌间质淋巴管生成中的作用机制及其临床意义。方法收集乳腺浸润性导管癌组织90例和乳腺纤维腺瘤组织30例,应用寡核苷酸探针原位杂交法检测组织中iNOS和COX-2的mRNA表达,另以Elivision免疫组化法检测淋巴管内皮细胞透明质酸受体1(LYVE-1)和血管内皮生长因子-C(VEGF-C)蛋白的表达情况,分析iNOS和COX-2与LYVE-1标记的淋巴管密度(LVD)以及VEGF-C的关系。结果在90例乳腺癌中iNOS、COX-2的mRNA阳性率分别为66.7%、68.9%,LVD为(8.03±2.26)个/HPF,VEGF-C表达阳性率为47.8%,与良性对照组比较均有显著差异(P<0.01)。iNOS mRNA表达与乳腺癌肿瘤大小、分期、LVD和VEGF-C表达呈正相关(P<0.01);COX-2 mRNA表达与肿瘤分级、淋巴结转移、分期和LVD呈正相关(P<0.05),与VEGF-C表达无显著相关(P>0.05);iNOS和COX-2的mRNA阳性表达呈正相关(P<0.05)。结论 iNOS和COX-2具有协同促进乳腺癌淋巴管生成及侵袭转移的作用,有望在乳腺癌的临床预后判断及靶向治疗中发挥作用。