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cyclooxygenase-2 expression is associated with initiation of hepatocellular carcinoma, while prostaglandin receptor-1 expression predicts survival

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World Journal of Gastroenterology 2016年第39期22卷 8798-8805页

作者： Hao-Jie Yang Jing-Hang Jiang Yu-ting Yang Xiang-Di Yang Zhe Guo Ya-Peng Qi Feng-Hua Zeng Ke-Lan Zhang Neng-Zhi Chen Bang-De Xiang Le-Qun Li Department of Hepatobiliary Surgery Affiliated Tumor Hospital of Guangxi Medical University Department of General Surgery The First People’s Hospital of Changde Department of General Surgery Second People’s Hospital of Jing Men Department of Chemotherapy Affiliated Tumor Hospital of Guangxi Medical University Department of Oncology Chenzhou No.1 People’s Hospital Department of Thyroid and Breast Surgery Central Hospital of Wuhan

AIM to determine whether cyclooxygenase-2(COX-2) and prostaglandin E1 receptor(EP1) contribute to disease and whether they help predict *** We retrospectively reviewed the records of 116 patients with hepatocellular carcinoma(HCC) who underwent surgery between 2008 and 2011 at our hospital. Expression of COX-2 and EP1 receptor was examined by immunohistochemistry of formalin-fixed, paraffinembedded tissues using polyclonal antibodies. Possible associations between immunohistochemical scores and survival were *** Factors associated with poor overall survival(OS) were alpha-fetoprotein > 400 ng/m L, tumor size ≥ 5 cm, and high EP1 receptor expression, but not high COX-2 expression. Disease-free survival was not significantly different between patients with low or high levels of COX-2 or EP1. COX-2 immunoreactivity was significantly higher in well-differentiated HCC tissues(Edmondson grade Ⅰ-Ⅱ) than in poorly differentiated tissues(Edmondson grade Ⅲ-Ⅳ)(P = 0.003). EP1 receptor immunoreactivity was significantly higher in poorly differentiated tissue than in well-differentiated tissue(P = 0.001).CONCLUSION COX-2 expression appears to be linked to early HCC events(initiation), while EP1 receptor expression may participate in tumor progression and predict survival.

关键词： cyclooxygenase-2 Hepatocellular carcinoma Liver resection Prognosis Prostaglandin E1 receptor

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EFFECTS OF cyclooxygenase-2 ANTISENSE VECTOR ON PROLIFERATION OF HUMAN CHOLANGIOCARCINOMA CELLS

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Chinese Medical Sciences Journal 2004年第2期19卷 89-92页

作者： Gao-songWu Sheng-quanZou Xiao-yongWu Fa-zuQiu DepartmentofGeneralSurgery TongjiHospitalTongjiMedicalCollegeHuazhongUniversityofScienceandTechnologyWuhan430030

Objective To transfect antisense vector of human cyclooxygenase-2 (COX-2) gene into COX-2 highly expressing chol-angiocarcinoma cell line QBC939 and explore its biological activities and role in carcinogenesis. Methods QBC939 cells were transfected with antisense vector of human COX-2 gene using LipoVecTM transfecting te-chnique. Transfected cells were selected with G418; COX-2 mRNA was examined using reverse transcription polymerase chain reaction (RT-PCR) and COX-2 protein expression was detected by immunocytochemistry using isozyme selective anti-bodies. The proliferative status of transfected cells was measured by using methabenzthiazuron (MTT) assay; Cell cycle and apoptosis were analyzed by using flow cytometry. Results RT-PCR showed a lower COX-2 mRNA level in antisense vector transfected cells and immunocytochemistry showed a weaker COX-2 protein expression in antisense vector transfected cells. The antisense vector transfected cells proli-ferative index decreased significantly (P27% ±1.91%) compared with that in QBC939 cells without transfection(16.35% ±2.87%), and the percentage of G0/G1 phase increased remarkably (P2 gene had no significant influence on the apoptosis in QBC939 cells (P> 0.05). Conclusion Transfection with antisense vector of human COX-2 gene could inhibit the proliferation of human cholan-giocarcinoma QBC939 cells.

关键词： cyclooxygenase-2 bile tract neoplasm gene transfer

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Near-infrared fluorescent probe for fast track of cyclooxygenase-2 in Golgi apparatus in cancer cells

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Frontiers of Chemical Science and Engineering 2020年第1期14卷 41-52页

作者： Bhaskar Gurram Miao Li Jiangli Fan Jingyun Wang Xiaojun Peng State Key Laboratory of Fine Chemicals Dalian University of TechnologyDalian 116024China School of Life Science and Biotechnology Dalian University of TechnologyDalian 116024China

cyclooxygenase-2(COX-2)has been used as an excellent traceable biomarker,and exists maximally in Golgi apparatus(Cancer cells).Celecoxib(CCB)is a selective inhibitor for COX-2,and has been used as one of non-steroidal anti-inflammatory *** we report the conjugation of nile blue(NB)with CCB via a six-carbon linkage to form a fluorescence probe NB-C6-CCB for the detection of ***-C6-CCB displays strong fluorescence with the emission peak centered at near-infrared wavelength(700 nm)in tumor cells or tumor tissues with high expression of ***,NB-C6-CCB can discriminate cancer cells(MCF-7)fluorescence intensity from normal ones(COS-7)in the co-culture medium under confocal *** localization of the NBC6-CCB preferentially points to the Golgi apparatus and increases the fluorescent *** competitive analysis(with CCB)and Native-PAGE analysis confirmed that NB-C6-CCB shows selective binding affinity towards COX-2 *** analysis with CCB(flow cytometry assay)revealed the fluorescence intensity fluctuation due to pretreatment of CCB with different concentrations,indicating that the NB-C6-CCB is a precise or sensitive probe for the *** tissue(depth:500μm),organs and mice imaging tests show excellent nearinfrared visualization,specific localization and identification of tumors.

关键词： cyclooxygenase-2 nile blue CCB Golgi apparatus NIR imaging

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cyclooxygenase-2 and the inflammogenesis of breast cancer

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World Journal of Clinical Oncology 2014年第4期5卷 677-692页

作者： Randall E Harris Bruce C Casto Zachary M Harris The Ohio State University Comprehensive Cancer Center The Ohio State University College of Medicine Columbus OH 43210-1351 United States College of Medicine and College of Public Health Center of Molecular Epidemiology and Environmental Health The Ohio State University Medical Center Columbus OH 43210-1351 United States

Cohesive scientific evidence from molecular, animal, and human investigations supports the hypothesis that constitutive overexpression of cyclooxygenase-2(COX-2) is a ubiquitous driver of mammary carcinogenesis, and reciprocally, that COX-2 blockade has strong potential for breast cancer prevention and therapy. Key findings include the following:(1) COX-2 is constitutively expressed throughout breast cancer development and expression intensifies with stage at detection, cancer progression and metastasis;(2) essential features of mammary carcinogenesis(mutagenesis, mitogenesis, angiogenesis, reduced apoptosis, metastasis and immunosuppression) are linked to COX-2-driven prostaglandin E2(PGE-2) biosynthesis;(3) upregulation of COX-2 and PGE-2 expression induces transcription of CYP-19 and aromatase-catalyzed estrogen biosynthesis which stimulates unbridled mitogenesis;(4) extrahe-patic CYP-1B1 in mammary adipose tissue converts paracrine estrogen to carcinogenic quinones with mutagenic impact; and(5) agents that inhibit COX-2 reduce the risk of breast cancer in women without disease and reduce recurrence risk and mortality in women with breast cancer. Recent sharp increases in global breast cancer incidence and mortality are likely driven by chronic inflammation of mammary adipose and upregulation of COX-2 associated with the obesity pandemic. The totality of evidence clearly supports the supposition that mammary carcinogenesis often evolves as a progressive series of highly specific cellular and molecular changes in response to induction of constitutive overexpression of COX-2 and the prostaglandin cascade in the "inflammogenesis of breast cancer".

关键词： Breast Cancer cyclooxygenase-2 Nonsteroidal anti-inflammatory drugs Inflammogenesis Estrogen Aromatase

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cyclooxygenase-2 plays a central role in the genesis of pancreatitis and associated lung injury

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Hepatobiliary & Pancreatic Diseases International 2005年第1期4卷 126-129页

作者： Gavin O'Brien Conor J Shields Desmond C Winter John P Dillon Department Of Academic Surgery Cork University Hospital and National University of Ireland Cork Ireland William O Kirwan and H. Paul RedmondCork Ireland

BACKGROUND: The exact mechanism by which cyclooxy- genase-2 (COX-2) promotes inflammation in pancreatitis in obscure. This study was undertaken to investigate the role of COX-2 inhibition in an animal model of pancreati- tis , a disease process characterized by a systemic inflamma- tory response and ensuing neutrophil-mediated lung injury. METHODS: Pancreatitis was induced in 24 Sprague-Daw- ley rats by intraperitoneal injection of 20% L-arginine (500 mg/100 g body weight). The animals were randomized into 3 groups (8 rats in each group); controls and rats with pancreatitis intravenously resuscitated with either normal saline (0.9% NaCl 3 ml/kg) at 24 and 48 hours or COX-2 inhibitor (parecoxib 1 mg/kg). Pancreatic and lung inju- ries were assessed histologically. Lung injury was assessed utilizing wet;dry ratio and myeloperoxidase activity to in- dicate pulmonary neutrophil infiltration. A Western blot was used to determine COX-2 protein expression in pancrea- tic tissue. RESULTS: The animals treated with COX-2 inhibitors dis- played significantly less pancreatic and lung injuries than their normal saline counterparts. Histological pancreatic and lung injury scores were significantly reduced (P 2 treated group. Lung wet: dry ratios were sig- nificantly improved and pulmonary neutrophil infiltration was attenuated in the COX-2 group (P2 protein expression. CONCLUSION: This study shows, for the first time in a rat model, that adjuvant COX-2 inhibition significandy attenu- ates the severity of both pancreatitis and its associated sys- temic inflammatory response and end-organ injury.

关键词： cyclooxygenase-2 pancreatitis genesis lung injury

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Involvement of eicosanoids in the pathogenesis of pancreatic cancer: the roles of cyclooxygenase-2 and 5-lipoxygenase

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World Journal of Gastroenterology 2014年第31期20卷 10729-10739页

作者： Lawrence M Knab Paul J Grippo David J Bentrem Department of Surgery Northwestern University Feinberg School of Medicine Robert H Lurie Comprehensive Cancer Center Northwestern University Jesse Brown VA Medical Center

The interplay between inflammation and cancer progression is a growing area of research. A combination of clinical, epidemiological, and basic science investigations indicate that there is a relationship between inflammatory changes in the pancreas and neoplastic progression. Diets high in ω-6 polyunsaturated fatty acids provide increased substrate for arachidonic acid metabolism by cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) to form eicosanoids. These eicosanoids directly contribute to pancreatic cancer cell proliferation. Both COX-2 and 5-LOX are upregulated in multiple cancer types, including pancreatic cancer. In vitro studies using pancreatic cancer cell lines have demonstrated upregulation of COX-2 and 5-LOX at both the mRNA and protein levels. When COX-2 and 5-LOX are blocked via a variety of mechanisms, cancer cell proliferation is abrogated both in vitro and in vivo. The mechanism of COX-2 has been shown to include effects on apoptosis as well as angiogenesis. 5-LOX has been implicated in apoptosis. The use of COX-2 and 5-LOX inhibitors in clinical studies in patients with pancreatic cancer has been limited. Patient enrollment has been restricted to those with advanced disease which makes evaluation of these drugs as chemopreventive agents difficult. COX-2 and 5-LOX expression have been shown to be present during the early neoplastic changes of pancreatic cancer, well before progression to invasive disease. This indicates that the ideal role for these interventions is early in the disease process as preventive agents, perhaps in patients with chronic pancreatitis or hereditary pancreatitis.

关键词： Arachidonic acid Eicosanoid cyclooxygenase-2 5-lipoxygenase Pancreatic cancer Inflammation

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Co-nanoencapsulated meloxicam and curcumin improves cognitive impairment induced by amyloid-beta through modulation of cyclooxygenase-2 in mice

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Neural Regeneration Research 2021年第4期16卷 780-786页

作者： Maria Eduarda Ziani Gutierrez Anne Suély Pinto Savall Edina da Luz Abreu Kelly Ayumi Nakama Renata Bem Dos Santos Marina Costa Monteiro Guedes Daiana SilvaÁvila Cristiane Luchese Sandra Elisa Haas Caroline Brandão Quines Simone Pinton Postgraduation Program in Biochemistry Federal University of Pampa(UNIPAMPA)UruguaianaRSBrazil Postgraduation Program in Pharmaceutical Science Federal University of Pampa(UNIPAMPA)UruguaianaRSBrazil Postgraduation Program in Biochemistry and Bioprospecting Federal University of Pelotas(UFPEL)Capão do LeãoRSBrazil

Alzheimer’s disease is a progressive brain disorder and complex mechanisms are involved in the physiopathology of Alzheimer’s ***,there is data suggesting that inflammation plays a role in its development and ***,some non-steroidal antiinflammatory drugs,such as meloxicam,which act by inhibiting cyclooxygenase-2 have been used as neuroprotective agents in different neurodegenerative disease *** purpose of this study was to investigate the effects of co-nanoencapsulated curcumin and meloxicam in lipid core nanocapsules(LCN)on cognitive impairment induced by amyloid-beta peptide injection in *** were prepared by the nanoprecipitation *** Swiss mice received a single intracerebroventricular injection of amyloid-beta peptide aggregates(fragment 25–35,3 nmol/3μL)or vehicle and were subsequently treated with curcumin-loaded LCN(10 mg/kg)or meloxicam-loaded LCN(5 mg/kg)or meloxicam+curcumin-co-loaded LCN(5 and 10 mg/kg,respectively).Treatments were given on alternate days for 12 days(i.e.,six doses,once every 48 hours,by intragastric gavage).Our data showed that amyloid-beta peptide infusion caused long-term memory deficits in the inhibitory avoidance and object recognition tests in *** the inhibitory avoidance test,both meloxicam and curcumin formulations(oil or co-loaded LCN)improved amyloid-beta-induced memory impairment in ***,only meloxicam and curcumin-co-loaded LCN attenuated non-aversive memory impairment in the object recognition ***,the beneficial effects of meloxicam and curcuminco-loaded LCN could be explained by the anti-inflammatory properties of these drugs through cortical cyclooxygenase-2 *** study suggests that the neuroprotective potential of meloxicam and curcumin co-nanoencapsulation is associated with cortical cyclooxygenase-2 *** study was approved by the Committee on Care and Use of Experimental Animal Resources,the Federal University of Pampa,Brazil(app

关键词： Alzheimer’s disease curcumin cyclooxygenase-2 lipid core nanocapsules meloxicam memory rats inflammation

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Adipose-derived stem cells inhibit dermal fibroblast growth and induce apoptosis in keloids through the arachidonic acid-derived cyclooxygenase-2/prostaglandin E2 cascade by paracrine

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Burns & Trauma 2021年第1期9卷 288-298页

作者： Jinxiu Yang Shiyi Li Leren He Minliang Chen Department of Burn and Plastic Surgery the Fourth Medical CentreChinese People’s Liberation Army General HospitalNo.51 Fucheng RoadHaidian DistrictBeijing100038China Chinese People’s Liberation Army General Hospital No.28 Fuxing RoadHaidian DistrictBeijing100853China 7th Department of Plastic Surgery Plastic Surgery HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeNo.33 Ba Dachu RoadShi Jingshan DistrictBeijing100144China

Background:The clinical features of keloids consist of aberrant proliferation,secretion,differentiation and apoptosis of keloid dermis-derived fibroblasts(KFBs).Notably,the apoptosis rate of KFBs is lower than the proliferation *** the anti-fibrotic effect of adipose-derived stem cells(ADSCs)on keloids has become a hot topic of research,the exact anti-fibrotic mechanism of the paracrine effect remains *** study aimed to find out how the conditioned medium of ADSCs(ADSC-CM)exerts an anti-fibrotic effect in ***:KFBs and ADSCs were extracted and ***,ADSC-CM was *** ADSC-CM could inhibit KFB growth and induce apoptosis was verified by the use of a cell counting kit-8,an 5-Ethynyl-2-deoxyuridine(Edu)kit and flow *** expressions of cyclooxygenase-1(COX-1),COX-2,caspase 3 and B-cell lymphoma-2(Bcl-2)in ADSC-CM-cultured KFBs were tested by real-time PCR and western *** clarify the role of COX-2 in ADSC-CM-induced KFB apoptosis,a specific COX-2 inhibitor,celecoxib,was applied to KFBs cultured in ***,we tested the production of arachidonic acid(AA)and prostaglandin E2(PGE2)by ***,we established a keloid transplantation model in a nude mouse to validate the therapeutic effect in ***:The proliferation ability of KFBs cultured in ADSC-CM was found to be weakened and apoptosis was significantly *** 3 expression was significantly upregulated and Bcl-2 was downregulated in ADSC-CM-cultured ***,ADSC-CM strikingly elevated COX-2 mRNA and protein expressions,but COX-1 expression was ***-2 inhibitors reduced ADSC-CM-induced ***,COX-2 inhibition blocked the elevation of caspase 3 and reversed the decrease in Bcl-2 ***-CM increased PGE2 levels by 1.5-fold and this effect was restrained by COX-2 *** the nude mouse model,expressions of AA,COX-2 and PGE2 were higher in the translated keloid tissues after ADSC-CM injecti

关键词： Keloids Adipose-derived stem cells Fibroblasts Apoptosis Anti-fibrosis cyclooxygenase-2 Arachidonic acid

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Role of cyclooxygenase-2 in gastric cancer development and progression

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World Journal of Gastroenterology 2013年第42期19卷 7361-7368页

作者： Jian Cheng Xiao-Ming Fan Department of Gastroenterology and Hepatology Jinshan Hospital of Fudan University

Although the incidence of gastric cancer has been declining in recent decades,it remains a major public health issue as the second leading cause of cancer death *** China,gastric cancer is still the main cause of death in patients with malignant *** patients are diagnosed at an advanced stage and mortality is ***-2(COX-2)is a ratelimiting enzyme in prostanoid synthesis and plays an important role in the development and progression of gastric *** expression of COX-2 in gastric cancer is upregulated and its molecular mechanisms have been *** pylori infection,tumor suppressor gene mutation and the activation of nuclear factor-kappa B may be responsible for the elevated expression of COX-2 in gastric *** mechanisms of COX-2 in the development and progression of gastric cancer are probably through promoting the proliferation of gastric cancer cells,while inhibiting apoptosis,assisting angiogenesis and lymphatic metastasis,and participating in cancer invasion and *** review is intended to discuss,comment and summarize recent research progress on the role of COX-2 in gastric cancer development and progression,and elucidate the molecular mechanisms which might be involved in the carcinogenesis.

关键词： cyclooxygenase-2 Gastric cancer Prostagladin Carcinogenesis Molecular mechanism

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Pelvic lipomatosis with cystitis glandularis managed with cyclooxygenase-2 inhibitor:A case report

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World Journal of Clinical Cases 2021年第17期9卷 4373-4380页

作者： Li-Cai Mo Song-Zhe Piao Hai-Hong Zheng Tao Hong Qin Feng Mang Ke Department of Urology Taizhou Hospital of Zhejiang Province Affiliated with Wenzhou Medical UniversityTaizhou 317000Zhejiang ProvinceChina Department of Pathology Taizhou Hospital of Zhejiang Province Affiliated with Wenzhou Medical UniversityTaizhou 317000Zhejiang ProvinceChina

BACKGROUND Pelvic lipomatosis(PL)is a rare benign condition with characteristic overgrowth of histologically benign fat and invasion and compression of pelvic organs,often leading to non-specific lower urinary tract symptoms(LUTS).Approximately 40%of patients with PL have cystitis glandularis(CG).The cause of PL combined with CG is poorly understood,and there is currently no effective *** CG with upper urinary tract obstruction even requires partial or radical bladder *** SUMMARY In this case,a patient suffering from PL with CG was treated by transurethral resection of bladder tumour(TUR-BT)and oral administration of celecoxib,a selective cyclooxygenase-2(COX-2)*** LUTS were alleviated,and the cystoscopy results improved *** showed upregulated COX-2 expression in the epithelium of TUR-BT samples,suggesting that COX-2 may participate in the pathophysiological process of PL combined with *** We report for the first time that celecoxib may be an effective treatment strategy for PL combined with refractory CG.

关键词： Pelvic lipomatosis Cystitis glandularis cyclooxygenase-2 Celecoxib Lower urinary tract symptoms Case report

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