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cyclooxygenase-2 expression as a predictor of outcome in colorectal carcinoma

World Journal of Gastroenterology 2012年第15期18卷 1793-1799页

作者： Jaudah Al-Maghrabi Abdelbaset Buhmeida Eman Emam Kari Syrjnen Abdulrahman Sibiany Mohmmad Al-Qahtani Mahmoud Al-Ahwal Department of Pathology King Abdulaziz UniversityJeddah 21589Saudi Arabia Center of Excellence in Genomic Medicine Research King Abdulaziz UniversityJeddah 21589Saudi Arabia Department of Oncology and Radiotherapy Turku University HospitalT-Hospital(Administration)FIN20521 TurkuFinland Department of Surgery King Abdulaziz UniversityJeddah 21589Saudi Arabia Department of Medicine Scientific Chair for Colorectal CancerKing Abdulaziz UniversityJeddah 21589Saudi Arabia

AIM:To correlate cyclooxygenase-2(COX-2)expression profile with clinical and pathological variables to assess their prognostic/predictive value in colorectal carcinoma(CRC).METHODS:Archival tumor samples were analyzed using immunohistochemistry for COX-2 expression in 94 patients with *** were diagnosed and treatedat the Departments of Surgery and Oncology,King Abdulaziz University Hospital,Saudi ***:Fifty-six percent of the tumors showed positive cytoplasmic COX-2 expression,whereas 44%of cases were completely *** were no significant correlations between COX-2 expression and sex,age,grade or tumor ***,COX-2 expression revealed a significant correlation with tumor stage(P=0.01)and distant metastasis(P=0.02),and a borderline association with lymph node involvement(P =0.07).Tumors with high COX-2 expression showed a higher recurrence rate than tumors with no expression(P26)difference in disease-free survival between COX-2-positive and negative tumors in favor of the ***-2 expression did not significantly predict disease-specific survival,which was much shorter for COX-2-positive *** multivariate(COX)models,COX-2 did not appear among the independent predictors of disease-free survival or disease-specific ***:COX-2 expression seems to provide useful prognostic information in CRC,while predicting the patients at high risk for recurrent disease.

关键词： Colorectal carcinoma cyclooxygenase-2 Immunohistochemistry Disease outcome Adjuvant therapy

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cyclooxygenase-2 polymorphisms and the risk of esophageal adeno-or squamous cell carcinoma

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World Journal of Gastroenterology 2009年第28期15卷 3493-3497页

作者： Jón O Kristinsson Paul van Westerveld Rene HM te Morsche Hennie MJ Roelofs T Wobbes Ben JM Witteman Adriaan CITL Tan Martijn GH van Oijen Jan BMJ Jansen Wilbert HM Peters Department of Gastroenterolog Radboud University Nijmegen Medical Center PO Box 9106500 HB Nijmegen The Netherlands Department of Surgery Radboud UniversityNijmegen Medical Center PO Box 9101 6500 HB NijmegenThe Netherlands Department of Gastroenterology Hospital Gelderse Vallei PO Box 9025 6710 HN Ede The Netherlands Department of Gastroenterology Canisius Wilhelmina Hospital Weg door Jonkerbos 100 6532 SZ Nijmegen The Netherlands

AIM： TO determine whether -1195 A→G and/or -765 G→C polymorphisms in cyclooxygenase-2 CCOX-2） may have a risk modifying effect on the development of esophageal carcinoma in a Dutch Caucasian population. METHODS： Two study groups were recruited, 252 patients with esophageal carcinoma and 240 healthy controls, matched for race, age, gender and recruiting area. DNA was isolated from whole blood and used for genotyping. PCR products were digested with restriction enzymes and products were analyzed by agarose gel electrophoresis. Odds ratios （OR） and 95% confidence intervals （CI） were estimated. RESULTS： The distribution of the -1195A→G polymorphism was significantly different in esophageal cancer patients compared to controls. The -1195 GG genotype resulted in a higher risk of developing esophageal adenocarcinoma （OR = 3.85, 95% CI： 1.45-10.3） compared with the -1195AA genotype as a reference. The -765 G→C genotype distribution was not different between the two groups. The GG/ GG haplotype was present more often in esophageal adenocarcinoma patients than in controls （OR = 3.45, 95% CI： 1.24-9.58; with AG/AG as a reference）. The same trends were observed in patients with squamous cell carcinomas, however, the results did not reach statistical significance. CONCLUSION： Presence of the COX-2 -1195 GG genotype and of the GG/GG haplotype may result in a higher risk of developing esophageal carcinoma.

关键词： Adenocarcinoma cyclooxygenase-2 Esophagus Genetic polymorphism Squamous cellcarcinoma

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Expression of cyclooxygenase-2 is associated with p53 accumulation in premalignant and malignant gallbladder lesions

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World Journal of Gastroenterology 2006年第21期12卷 3425-3429页

作者： Mateja Legan Bo(s|ˇ)tjan Luzar Vera Ferlan Marolt Andrej C(o|¨)r Institute for Histology and Embryology Medical Faculty University of Ljubljana Korytkova 21000 LjubljanaSlovenia Institute of Pathology Medical Faculty University of Ljubljana Korytkova 21000 LjubljanaSlovenia

AIM： To examine the relationship between cyclooxygenase-2 （COX-2） overexpression and p53 accumulation in gallbladder carcinoma and its precursor ***： Sixty-eight gallbladder tissue samples comprising 14 cases of normal gallblader epithelium, 27 cases of dysplasia （11 low-grade dyplasia and 16 high-grade dysplasia） and 27 adenocarcinomas were evaluated by immunohistochemistry for COX-2 expression and p53 accumulation. The relationship among COX-2 expression, p53 accumulation and clinicopathological characteristics was ***： COX-2 was expressed in 14.3% of normal gallbladder epithelium, 70.3% of dysplastic epite hlium, and 59.2% of adenocarcinomas. When divided into low- and high-grade dysplasia, COX-2 was positive in 5 （45.4%） cases of low-grade and 2d （87.5%） of high- grade dysplasia （P = 0.019）. Accumulation of p53 was detected in 5 （32.2%） cases of high-grade dysplasia and in 23 （48.2%） of carcinomas. No p53 accumulation was found in normal epithelium or low-grade dysplasia. COX-2 overexpression was observed in 27 of 28 （94.4%） cases with p53-accumulation in comparison with 20 （40.0%） out of 50 cases without p53 accumulation （P 〈 0.001）.CONCLUSION： The significant differences in COX-2 expression among normal epithelium, low-grade dysplasia and high-grade dysplasia suggest that overexpression of COX-2 enzyme is an early event in gallbladder carcinogenensis. Furthermore, since accumulation of p53 correlates with COX-2 expression, COX-2 overexpression observed in gallbladder high-grade dysplasia and carcinoma might be partly due to the dysfunction of p53.

关键词： Gallbladder Carcinogenesis cyclooxygenase-2 p53 Immunohystochemistry

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UP-REGULATION OF cyclooxygenase-2 GENE EXPRESSION CORRELATES WITH TUMOR ANGIOGENESIS IN HUMAN BREAST CANCER

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Chinese Journal of Cancer Research 2003年第2期15卷 149-151,156页

作者：代志军王西京刘小旭康华峰姜建涛管海涛张淑群薛兴欢薛锋杰 Department of Oncology Second Hospital Xi'an Jiaotong University

Objective: To study the relationship between cyclooxygenase-2 (COX-2) expression and tumor angiogenesis in human breast cancer. Methods: Archival primary breast carcinomas (n = 62), adjacent ductal carcinoma in situ (DCIS, n = 13) and DCIS alone (n = 5) were analyzed for COX-2 and VEGF expression by immunohistochemistry using specific monoclonal antibodies. Microvessel density (MVD) was also examined the using CD34 staining. Results: A significant correlation was found between COX-2 and VEGF expression (P2 and VEGF were significantly correlated with MVD (P2 and VEGF genes were overexpressed in tumor specimens as compared with normal epithelia. Conclusion: COX-2 is related to tumor angiogenesis in breast cancer. It is likely that VEGF is one of the most important mediators of the COX-2 angiogenic pathway.

关键词： Breast carcinoma cyclooxygenase-2 VEGF Microvessel density

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cyclooxygenase-2 promoter polymorphism -899G/C is associated with hepatitis B-related liver cancer in a Chinese population of Gansu province

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Chinese Medical Journal 2011年第24期000卷 4193-4197页

作者： HE Jian-hong LI Yu-min ZHANG Quan-bao REN Zhi-jian LI Xun ZHOU Wen-ce ZHANG Hui MENG Wen-bo HE Wen-ting The Second Department of General Surgery the First Hospital ofLanzhou University Lanzhou Gansu 730000 China Department of General Surgery the Second Hospital of LanzhouUniversity Lanzhou Gansu 730000 China Key Laboratory of Digestive System Tumors of Gansu Province Lanzhou Gansu 730000 China

Background Hepatitis B virus infection is closely related to hepatocellular carcinoma （HCC）. cyclooxygenase-2 （COX-2） is overexpressed in HCC and considered to play a role in hepatic carcinogenesis. In this study, we analyzed the polymorphism of COX-2 promoter -899G/C in healthy controls, chronic hepatitis B （CHB） patients, liver cirrhosis patients, and hepatocellular carcinoma （HCC） patients, to investigate the relationship between COX-2 -899G/C polymorphism and the risk for hepatitis B-related liver cancer in a Chinese population from Gansu province. Methods Patients were divided into four groups： 300 patients with CHB, 300 patients with liver cirrhosis, 300 patients with HCC, and 300 healthy controls. The polymorphism of COX-2 -899G/C was detected by PCR-TaqMan probes. The results were analyzed by SPSS 17.0. Results The COX-2 -899G/C genotypes were GG, GC, and CC. Frequencies in CHB were 87.00%, 12.67%, 0.33%; in liver cirrhosis were 85.33%, 14.00%, 0.67%; in HCC were 77.00%, 21.67%, 1.33%; and in healthy controls were 90.67%, 9.00%, 0.33%, respectively. COX-2 -899C carriers may have an increased risk for hepatitis B-related liver cancer. Compared with the frequency of GG genotype, there were significant differences in the frequency of GC genotype between HCC and healthy control groups （0R=2.835, 95%C/： 1.751-4.589）; HCC and CHB groups （OR=1.933, 95%C/： 1.248-2.994）; and HCC and liver cirrhosis groups （OR=1. 175, 95%C/： 1.119-2.628）. Stratification analyses showed that COX-2 -899C allele carriers with a drinking history are more susceptible to develop HCC. Conclusion COX-2 -899C genotype may increase the susceptibility of individuals to hepatitis B-related liver cancer in Gansu province, China.

关键词： cyclooxygenase-2 polymorphisms hepatitis B-related liver cancer

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cyclooxygenase-2 Blockade Inhibits Accumulation and Function of Myeloid-derived Suppressor Cells and Restores T Cell Response after Traumatic Stress

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2014年第2期34卷 234-240页

作者：李仁杰刘琳高伟宋先舟白祥军李占飞 Department of Traumatic Surgery Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Department of Biochemistry and Molecular Biology Tongji Medical College Huazhong University of Science and Technology

Myeloid-derived suppressor cells （MDSCs） play a crucial role in T cell dysfunction, which is related to poor outcome in patients with severe trauma. cyclooxygenase-2 （Cox-2） contributes to immune disorder in trauma and infection via production of prostaglandin E2. However, the role of Cox-2 in the accumulation and function of MDSCs after traumatic stress has not been fully elucidated. In the present study, we treated murine trauma model with NS398, a selective Cox-2 inhibitor. Then the percentages of CD1 lb＋/Gr-l＋ cells, proliferation and apoptosis of CD4＋ T cells were determined. Ar- ginase activity and arginase-1 （Arg-1） protein expression of splenic CDllb＋/Gr-I＋ cells, and de- layed-type hypersensitivity （DTH） response were analyzed. The results showed that Cox-2 blockade significantly decreased the percentages of CD1 lb＋/Gr-l＋ cells in the spleen and bone marrow 48 and 72 h after traumatic stress. NS398 inhibited arginase activity and down-regulated the Arg-1 expression of splenic CD1 lb＋/Gr-l＋ ceils. Moreover, NS398 could promote proliferation and inhibit apoptosis of CD4＋ T cells. It also restored DTH response of traumatic mice. Taken together, our data revealed that Cox-2 might play a pivotal role in the accumulation and function of MDSC after traumatic stress.

关键词： myeloid-derived suppressor cells trauma T cell dysfunction cyclooxygenase-2

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Precise Detection and Visualization of cyclooxygenase-2 for Golgi Imaging by a Light-Up AggregationInduced Emission-Based Probe

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CCS Chemistry 2022年第2期4卷 456-463页

作者： Yuchao Luo Song Zhang Hui Wang Quan Luo Zhigang Xie Bin Xu Wenjing Tian State Key Laboratory of Supramolecular Structure and Materials Department of ChemistryJilin UniversityChangchun 130012 Department State Key Laboratory of Polymer Physics and Chemistry Institution Changchun Institute of Applied ChemistryChangchun 130022

Precision-targeted detection of cancer in a rapid and sensitive fashion remains a significant challenge in prevention,management,and in particular,***,we have designed and synthesized a unique cyclooxygenase-2(COX-2)fluorescence probe,dimethylamine-9,10-distyrylanthracene-indomethacin(NDSA-IMC),that could visualize the site of highly expressed COX-2 in the Golgi apparatus of cancer cells,using 9,10-diatyrylanthracene derivative as the luminous unit and a selective inhibitor,indomethacin(IMC),as the recognizing moiety for *** an aqueous solution,the free state NDSA-IMC showed a weak emission in the absence of COX-2 but enhanced emission in the presence of the enzyme due to the restriction of intramolecular motion of aggregation-induced emission-active NDSA-IMC when bound to *** imaging and flow cytometry experiments indicated that NDSA-IMC could discriminate between cancer and normal cells and visualize the Golgi apparatus of cancer cells via specific targeting of ***,NDSA-IMC might potentially detect early cancer lesions and ultimately mitigate the population of cancer burden in society.

关键词： cyclooxygenase-2 Golgi aggregation-induced emission

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A Phase Ⅱ Clinical Trial of Celecoxib Combined with Platinum-Based Regimen as First-Line Chemotherapy for Advanced Non-Small Cell Lung Cancer Patients with cyclooxygenase-2 Positive Expression

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Chinese Journal of Cancer Research 2009年第1期21卷 1-12页

作者： Jun Zhao Zhi-jie Wang Jian-chun Duan Qing-zhi Guo Hua Bai Lu Yang Tong-tong An Xin Wang Yu-yan Wang Mei-na Wu Xu-yi Liu Jie Wang Key Laboratory of Carcinogenesis and Translational Research （Ministry of Education） Department of Thoracic Medical Oncology Peking University School of Oncology Beijing Cancer Hospital ＆ Institute Beijing 100142 China

Objective： To evaluate the efficacy and safety of celecoxib treatment of advanced non-small cell lung cancer （NSCLC）, and combined therapy by molecular analysis. plus platinum-doublet as first-line chemotherapy in to determine the subgroup benefiting from celecoxib Methods： A total of 44 treatment-naive patients of advanced NSCLC with positive cyclooxygenase-2 （COX-2） expression confirmed by immunohistochemical （IHC） staining were designed to receive celecoxib plus platinum-doublet chemotherapy （cisplatin plus gemcitabine, novelbine or docetaxol） from February 2005 to May 2007. On 5-7 day before chemotherapy, 400 mg celecoxib was administered twice a day orally until obvious evidence of disease progression or intolerable toxicity was found. Adverse events were recorded according to NCI-CTC criteria. The primary endpoint was overall survival （OS）. The secondary endpoints included progression-free survival （PFS）, 1-year survival rate, response rate （RR） and safety. Additionally, we detected epithelial growth factor receptor （EGFR） status including EGFR gene amplification by real-time PCR and gene mutations by DHPLC followed by sequencing. Results： The response rate was 45% （20/44）, and the disease control rate （DCR） was 59% （26/44）. The median progression-free survival time and median survival time were 6 m and 18 m, respectively. The l-year survival rate was 68%. Chemotherapy cycle numbers and best response were found to be the predictive factors for PFS by COX model analysis （P=0.023 and P=0.000, respectively）. No factor was found to affect OS. The most common toxicities included neutropenia and nausea/vomit. EGFR gene amplification was an independent prognostic factor influencing OS （P=0.0002）. Patients with EGFR mutations （exon 21） had a tendency of disease progression （P=0.041）. Conclusion： Encouraging activities of celecoxib combined with platinum-doublet chemotherapy were demonstrated in treatment-naive patients with advanced NSCLC, with good tolerances. For

关键词： cyclooxygenase-2 Epithelial growth factor receptor Non-small-cell lung cancer

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Expression of cyclooxygenase-2 and Transforming Growth Factor-Beta 1 in Patients with the Early Recurrence of Hepatocellular Carcinoma Following Hepatectomy

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Surgical Science 2012年第6期3卷 322-331页

作者： Takayuki Nakase Masaki Ueno Kazuhisa Uchiyama Nariaki Matsuura Hiroki Yamaue Department of Functional Diagnostic Science Osaka University Graduate School of Medicine Osaka Japan Second Department of Surgery School of Medicine Wakayama Medical University Wakayama Japan

Background: cyclooxygenase-2 (COX-2) and transforming growth factor-beta1 (TGF-β1) are modulated in variety cancers including Hepatocellular carcinoma (HCC). However, there is a paucity of data concerning their role in the pathologic process of recurrence of HCC following hepatectomy. We herein assessed the role of the hepatic expression of COX-2 and TGF-β as predictors for patients with early recurrence within 2 years of HCC diagnosis. Methods: Sixty patients with HCC who underwent curative hepatectomy between 2000 and 2003 were entered in the present study. The immunoreactivity and distribution patterns of COX-2 and TGF-β1 were examined in both the HCC and the adjacent nonHCC tissues of the liver. Risk factors of tumor recurrence within 2 years, including COX-2 and TGF-β1 expression, were investigated by univariate and multivariate analyses. Results: Among 60 patients, 31 patients had early recurrences within 2 years and 14 patients recurred after 2 years following surgery. Patients with low COX-2 expression in the HCC tissues and adjacent nonHCC tissues had favorable disease-free survival (p = 0.002 and p β1 expression in the nonHCC tissues had also longer disease-free survival (p = 0.045). Based on the expression patterns of COX-2 and TGF-β1, patients with low COX-2 and positive TGF-β1 expression in the nonHCC tissues had favorable overall and disease-free survival (p β1 signaling in nontumor tissues suggested high risk of recurrence and poor survival to the HCC patients following hepatectomy.

关键词： cyclooxygenase-2 Transforming Growth Factor-Beta1 Hepatocellular Carcinoma Early Recurrence Hepatectomy

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cyclooxygenase-2 and Decidual Immune Cells

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Reproductive and Developmental Medicine 2019年第3期3卷 177-184页

作者： Si-Yao Ha Hui-Li Yang Zhen-Zhen Lai Lu-Yu Ruan Jia-Wei Shi Ming-Qing Li Laboratory for Reproductive Immunology Institute of Obstetrics and GynecologyHospital of Obstetrics and GynecologyFudan UniversityShanghai 200080China Laboratory for Reproductive Immunology Shanghai Key Laboratory of Female Reproductive Endocrine Related DiseasesHospital of Obstetrics and GynecologyFudan UniversityShanghai 200011China Laboratory for Reproductive Immunology NHC Key Laboratory of Reproduction Regulation(Shanghai Institute of Planned Parenthood Research)Fudan UniversityShanghai 230032China

cyclooxygenase-2(COX-2)is a rate-limiting enzyme in arachidonic acid(AA)***-2 and its products(prostanoids)serve versatile biological functions during *** evidences demonstrate special reprogramming of COX-2-catalyzing AA metabolism in decidual immune cells(DICs),particularly in decidual macrophages,corresponding to special gestational *** review summarizes the reprogramming of COX-2-catalyzing AA metabolism in DICs as well as the immunoregulation of diverse COX-2-generating prostanoids in DICs during the different phases of gestation.

关键词： cyclooxygenase-2 Decidual Immune Cell Metabolism Pregnancy Prostanoid

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