Journal of Pathology and Translational Medicine

Original Articles

Expression of HuR and Cyclooxygenase-2 in Nodular Fasciitis and Low-Grade Sarcoma: An Immunohistochemical Study: Hyun-Jin Son, Tae-Hwa Baek, Seung Yun Lee, Joo-Heon Kim, Dong-Wook Kang, Hye-Kyung Lee, Mee-Ja Park; Korean J Pathol. 2014;48(4):270-275. Published online August 26, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.4.270

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Background

Nodular fasciitis is the most common reactive mesenchymal lesion to be misidentified as a type of sarcoma. HuR is an mRNA-binding protein that can stabilize cyclooxygenase-2 (COX-2) mRNA leading to COX-2 overexpression. The aim of this study is a comparison of the expressions of COX-2 and HuR and the relationships between their expressions and the clinicopathological parameters in nodular fasciitis and low-grade sarcoma.

Methods

We measured the expression of HuR and COX-2 in 21 cases of nodular fasciitis and 37 cases of low-grade sarcoma using immunohistochemistry.

Results

The frequency of cytoplasmic immunoreactivity for HuR was 5 of 21 cases of nodular fasciitis (23.8%) and 23 of 37 cases of low-grade sarcoma (62.1%) (p=.013). COX-2 expression was moderate or strong in nodular fasciitis (12/21, 57.1%) and in low-grade sarcoma (29/37, 78.4%) (p=.034). In addition, a significant difference existed between these two entities in terms of the relationship between moderate or strong COX-2 expression and HuR cytoplasmic immunoreactivity (p=.009). Moderate or strong COX-2 immunoreactivity correlated with nuclear (p=.016) or cytoplasmic HuR (p=.024) expression in low-grade sarcoma but not in nodular fasciitis.

Conclusions

This study suggests that HuR and COX-2 expression may be useful to differentiate nodular fasciitis from low-grade sarcoma.

Citations

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Nodular Fasciitis of the Cubital Fossa in a Young Female Mimicking a Neurogenic Tumor
Hyung-Joon Lee, Ji-Kang Park, Seok-Won Kim, Min-Boo Kim
Journal of the Korean Orthopaedic Association.2023; 58(2): 179. CrossRef
Nodular fasciitis of the anterior chest wall mimicking myxofibrosarcoma: A case report and literature review
Antonino Cattafi, Mariarosaria Galeano, Pietro Pitrone, Carmelo Sofia, Maria Adele Marino, Giorgio Ascenti, Maria Lentini, Antonio Ieni, Roberta Cardia, Alfio Luca Costa, Dario Familiari, Mario Barone, Francesco Monaco, Michele Rosario Colonna
Radiology Case Reports.2021; 16(6): 1557. CrossRef

Cyclooxygenase-2 Expression and Its Prognostic Significance in Clear Cell Renal Cell Carcinoma: Ji Won Lee, Jeong Hwan Park, Ja Hee Suh, Kyung Han Nam, Ji-Young Choe, Hae Yoen Jung, Ji Yoen Chae, Kyung Chul Moon; Korean J Pathol. 2012;46(3):237-245. Published online June 22, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.3.237

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Abstract PDF

Background

The prognostic value of cyclooxygenase-2 (COX-2) in human renal cell carcinoma (RCC) remains unclear. The purposes of this study are to elucidate the clinical significance of COX-2 in clear cell RCC (CCRCC) and to assess the treatment effect of COX-2 inhibition on CCRCC cell lines.

Methods

Using tumor samples obtained from 137 patients who had undergone nephrectomy at Seoul National University Hospital, we evaluated COX-2 expression on immunohistochemistry. Moreover, we performed the cell proliferation assay using 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl-2H tetrazolium bromide (MTT) and cell invasion assay. Thus, we evaluated the effect of meloxicam, an inhibitor of COX-2, in two human CCRCC cell lines.

Results

Cancer-specific survival (p=0.038) and progression-free survival (p=0.031) were shorter in the COX-2 high expression group. A multivariate logistic regression model showed that COX-2 expression was an independent risk factor for pTNM stage and Fuhrman nuclear grade. The MTT assay revealed that COX-2 inhibition led to the suppression of the proliferation of CCRCC cell lines. Moreover, it also reduced their invasion capacity.

Conclusions

This study postulates that COX-2 is a poor prognostic indicator in human CCRCC, suggesting that COX-2 inhibition can be a potential therapy in CCRCC.

Citations

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Arachidonic acid metabolism as a therapeutic target in AKI-to-CKD transition
Xiao-Jun Li, Ping Suo, Yan-Ni Wang, Liang Zou, Xiao-Li Nie, Ying-Yong Zhao, Hua Miao
Frontiers in Pharmacology.2024;[Epub] CrossRef
The tumor microenvironment and immune targeting therapy in pediatric renal tumors
Amy B. Hont, Benoit Dumont, Kathryn S. Sutton, John Anderson, Alex Kentsis, Jarno Drost, Andrew L. Hong, Arnauld Verschuur
Pediatric Blood & Cancer.2023;[Epub] CrossRef
Free-fatty acid receptor-1 (FFA1/GPR40) promotes papillary RCC proliferation and tumor growth via Src/PI3K/AKT/NF-κB but suppresses migration by inhibition of EGFR, ERK1/2, STAT3 and EMT
Priyanka F. Karmokar, Nader H. Moniri
Cancer Cell International.2023;[Epub] CrossRef
Flavonoids derived from Anemarrhenae Rhizoma ameliorate inflammation of benign prostatic hyperplasia via modulating COX/LOX pathways
Xiaotong Cao, Ying Shang, Weigui Kong, Shuqing Jiang, Jun Liao, Ronghua Dai
Journal of Ethnopharmacology.2022; 284: 114740. CrossRef
Kirenol, darutoside and hesperidin contribute to the anti-inflammatory and analgesic activities of Siegesbeckia pubescens makino by inhibiting COX-2 expression and inflammatory cell infiltration
Yu-Sang Li, Jian Zhang, Gui-Hua Tian, Hong-Cai Shang, He-Bin Tang
Journal of Ethnopharmacology.2021; 268: 113547. CrossRef
Differential expression of cyclooxygenase-2 and cyclin D1 in salivary gland tumors
Jefferson da Rocha Tenório, Leorik Pereira da Silva, Marília Gabriela de Aguiar Xavier, Thalita Santana, George João Ferreira do Nascimento, Ana Paula Veras Sobral
European Archives of Oto-Rhino-Laryngology.2018; 275(9): 2341. CrossRef
Retrospective evaluation of COX‐2 expression, histological and clinical factors as prognostic indicators in dogs with renal cell carcinomas undergoing nephrectomy
S. Carvalho, A. L. Stoll, S. L. Priestnall, A. Suarez‐Bonnet, K. Rassnick, S. Lynch, I. Schoepper, G. Romanelli, P. Buracco, M. Atherton, E. M. de Merlo, A. Lara‐Garcia
Veterinary and Comparative Oncology.2017; 15(4): 1280. CrossRef
Functional PTGS2 polymorphism-based models as novel predictive markers in metastatic renal cell carcinoma patients receiving first-line sunitinib
Arancha Cebrián, Teresa Gómez del Pulgar, María José Méndez-Vidal, María Luisa Gonzálvez, Nuria Lainez, Daniel Castellano, Iciar García-Carbonero, Emilio Esteban, Maria Isabel Sáez, Rosa Villatoro, Cristina Suárez, Alfredo Carrato, Javier Munárriz-Ferránd
Scientific Reports.2017;[Epub] CrossRef
COX-2 expression in ovarian cancer: an updated meta-analysis
Haiming Sun, Xuelong Zhang, Donglin Sun, Xueyuan Jia, Lidan Xu, Yuandong Qiao, Yan Jin
Oncotarget.2017; 8(50): 88152. CrossRef
COX-2 Expression in Renal Cell Carcinoma and Correlations with Tumor Grade, Stage and Patient Prognosis
Hedieh Moradi Tabriz, Marzieh Mirzaalizadeh, Shahram Gooran, Farzaneh Niki, Maryam Jabri
Asian Pacific Journal of Cancer Prevention.2016; 17(2): 535. CrossRef
Lipidomic Signatures and Associated Transcriptomic Profiles of Clear Cell Renal Cell Carcinoma
Kosuke Saito, Eri Arai, Keiko Maekawa, Masaki Ishikawa, Hiroyuki Fujimoto, Ryo Taguchi, Kenji Matsumoto, Yae Kanai, Yoshiro Saito
Scientific Reports.2016;[Epub] CrossRef
Intratumoral expression of cyclooxygenase-2 (COX-2) is a negative prognostic marker for patients with cutaneous melanoma
Łukasz Kuźbicki, Dariusz Lange, Agata Stanek-Widera, Barbara W. Chwirot
Melanoma Research.2016; 26(5): 448. CrossRef
New Insights on COX-2 in Chronic Inflammation Driving Breast Cancer Growth and Metastasis
Honor J. Hugo, C. Saunders, R. G. Ramsay, E. W. Thompson
Journal of Mammary Gland Biology and Neoplasia.2015; 20(3-4): 109. CrossRef
The role of prostaglandin E2 in renal cell cancer development: future implications for prognosis and therapy
Katarzyna Kaminska, Cezary Szczylik, Fei Lian, Anna M Czarnecka
Future Oncology.2014; 10(14): 2177. CrossRef
Genomics and epigenomics of clear cell renal cell carcinoma: Recent developments and potential applications
Małgorzata Rydzanicz, Tomasz Wrzesiński, Hans A.R. Bluyssen, Joanna Wesoły
Cancer Letters.2013; 341(2): 111. CrossRef
Quantitative Assessment of the Association of COX-2 (Cyclooxygenase-2) Immunoexpression with Prognosis in Human Osteosarcoma: A Meta-Analysis
Zhe Wang, Maolin He, Zengming Xiao, Hao Wu, Yang Wu, Dominique Heymann
PLoS ONE.2013; 8(12): e82907. CrossRef

Detection of Survivin and COX-2 in Thyroid Carcinoma: Anaplastic Carcinoma Shows Overexpression of Nuclear Survivin and Low COX-2 Expression: Young A Kim, Meesoo Chang, Young Joo Park, Ji Eun Kim; Korean J Pathol. 2012;46(1):55-60. Published online February 23, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.1.55

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Abstract PDF

Background

Overexpression of survivin, a member of the inhibitors of apoptosis protein, has been reported in various carcinomas, and its interaction with cyclooxygenase 2 (COX-2) results in accelerated tumor progression. The purpose of this study is to investigate the immunohistochemical expression of survivin and COX-2 in benign and malignant thyroid tissues and to define its association with pathologic and clinical features.

Methods

We examined expression of survivin and COX-2 by immunohistochemistry in 334 benign and malignant thyroid tissues and evaluated their clinical significance.

Results

Expression of survivin showed an increase along the spectrum of thyroid carcinoma progression; rarely positive in adenomatous goiter, moderately positive in papillary carcinoma, and strongly positive in anaplastic carcinoma (AC). Papillary microcarcinoma revealed the highest COX-2 positivity and AC demonstrated the lowest positivity among thyroid cancers. Node negative carcinomas showed higher COX-2 expression than node positive tumors. Survivin expression did not correlate with COX-2.

Conclusions

Our findings suggest that survivin overexpression may be related to the pathogenesis of AC and can be a predictor of disease progression. COX-2 may be involved in the early phase of thyroid carcinoma.

Citations

Citations to this article as recorded by

Survivin as a diagnostic and therapeutic marker for thyroid cancer
Mohammad-Reza Mahmoudian-Sani, Arash Alghasi, Ali Saeedi-Boroujeni, Akram Jalali, Mohammad Jamshidi, Ali Khodadadi
Pathology - Research and Practice.2019; 215(4): 619. CrossRef
TFAP2B overexpression contributes to tumor growth and progression of thyroid cancer through the COX-2 signaling pathway
Xiaoyan Fu, Huayong Zhang, Zhipeng Chen, Zhongyuan Yang, Dingbo Shi, Tianrun Liu, Weichao Chen, Fan Yao, Xuan Su, Wuguo Deng, Miao Chen, Ankui Yang
Cell Death & Disease.2019;[Epub] CrossRef
Expression of nm23-H1 and COX-2 in thyroid papillary carcinoma and microcarcinoma
Marija Milkovic Perisa, Bozena Sarcevic, Koraljka Gall Troselj, Kresimir Grsic, Sanda Sitic, Sven Seiwerth
Oncology Letters.2017; 13(5): 3547. CrossRef
The Diagnostic Usefulness of HMGA2, Survivin, CEACAM6, and SFN/14-3-3 δ in Follicular Thyroid Carcinoma
Min Hye Jang, Kyeong Cheon Jung, Hye Sook Min
Journal of Pathology and Translational Medicine.2015; 49(2): 112. CrossRef
Evaluation of survivin expression and its prognostic value in papillary thyroid carcinoma
Sonja Selemetjev, Tijana Isic Dencic, Ilona Marecko, Jelena Jankovic, Ivan Paunovic, Svetlana Savin, Dubravka Cvejic
Pathology - Research and Practice.2014; 210(1): 30. CrossRef

Effect of Selective Cyclooxygenase 2 Inhibitor in TCDD Pre-exposed Thyroid Papillary Carcinoma Cell Line.: Hae Sung Kim, Kwang Sung Ahn, Jeong Hyeon Lee, Yang Seok Chae, Nam Hee Won, Jong Sang Choi, Chul Hwan Kim; Korean J Pathol. 2011;45(1):1-8.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.1.1

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Abstract PDF

BACKGROUND
Cyclooxygenase 2 (COX-2) is related to carcinogenesis and progression of cancer. COX-2 has been detected in thyroid cancer. This suggests that COX-2 inhibitor may be useful to control the growth of thyroid cancer cells as well as the progression of thyroid cancer. Tetrachlorodibenzodioxin (TCDD), acting as an inflammatory cytokine, directly induces the expression of COX-2. We examine whether TCDD controls the effect of COX-2 inhibitor on thyroid cancer cells.
METHODS
The effects of TCDD and celecoxib on thyroid papillary carcinoma cell line (SNU790) were examined using cell proliferation and fluorescence-activated cell sorting analysis. Western blot analysis was performed to determine the expressed COX-2 levels and the cell cycle-related proteins. The matrix metalloproteinase-2 (MMP-2) expression and gelatinolytic activity were examined using real time-polymerase chain reaction and zymography.
RESULTS
TCDD directly induced the growth of SNU790 and the expression of cyclin D1, cyclin A, cyclin E, p21 and COX-2. Celecoxib suppressed the growth of SNU790 and the expression of cyclin D1 and cyclin E. Celecoxib reduced the MMP-2 expression and the gelatinolytic activity, but those effects were decreased in the SNU790 by either pre-treatment with TCDD or co-treatment with TCDD and celecoxib.
CONCLUSIONS
Celocoxib effect is directly reduced depending on the exposure to TCDD. TCDD exposure should be considered in the treatment with Celecoxib.

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Histone H3 phosphorylation, immediate-early gene expression, and the nucleosomal response: a historical perspective1This article is part of Special Issue entitled Asilomar Chromatin and has undergone the Journal’s usual peer review process.
Shannon Healy, Protiti Khan, Shihua He, James R. Davie
Biochemistry and Cell Biology.2012; 90(1): 39. CrossRef

Expression of Cyclooxygenase-2 and Embryonic Lethal Abnormal Vision-Like Protein HuR in Gallbladder Carcinoma.: Sung Im Do, Gou Young Kim, Sung Jig Lim, Youn Wha Kim; Korean J Pathol. 2010;44(1):42-47.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.1.42

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Abstract PDF

BACKGROUND
Cyclooxygenase-2 (COX-2) is an enzyme that promotes proliferation of tumor cells. HuR is a member of the family of embryonic lethal abnormal vision-like proteins. Recent studies show that cytoplasmic HuR stabilizes the mRNA of COX-2 and regulates the expression of COX-2. Moreover, cytoplasmic HuR expression is associated with a poorer prognosis for patients with some cancers. The aim of this study was to investigate the expression patterns of and the relationship between COX-2 and HuR in gallbladder carcinoma.
METHODS
We analyzed COX-2 and HuR expression by immunohistochemical staining of 108 gallbladder carcinomas.
RESULTS
COX-2 expression and nuclear and cytoplasmic HuR expression were seen in, respectively, 61 (56.5%), 77 (71.3%), and 4 (3.7%) cases. COX-2 and nuclear HuR were simultaneously expressed in 44 of the 108 samples without any quantitative association between the levels of each. COX-2 expression correlated with tumor stage, differentiation (based on histology), lymph node metastasis, perineural invasion, and survival. Nuclear and cytological expression of HuR did not correlate with any clinical parameters.
CONCLUSIONS
COX-2 expression but not HuR may play an important role in the prognosis of patients with gallbladder carcinoma.

Citations

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Prognostic molecular markers in resected extrahepatic biliary tract cancers; a systematic review and meta-analysis of immunohistochemically detected biomarkers
Robert P Jones, Nicholas TE Bird, Richard A Smith, Daniel H Palmer, Steven W Fenwick, Graeme J Poston, Hassan Z Malik
Biomarkers in Medicine.2015; 9(8): 763. CrossRef

Effects of Selective Cyclooxygenase-2 Inhibitor NS-398 Pretreatment on the Rat Spinal Cord after Contusion Injury.: Hyeon Dae Cheong, Joo Kyung Sung, In Suk Ham, Ku Seong Kang, Joung Ok Kim, Jung Wan Kim, Tae In Park, Yoon Kyung Sohn; Korean J Pathol. 2006;40(4):255-262.

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Abstract PDF: BACKGROUND
Secondary spinal cord injury (SCI) that follows an initial mechanical insult can exacerbate the overall damage, limit the restorative processes and eventually lead to an in- creased neurological deficit. We hypothesized that selective inhibition of cyclooxygenase-2 (COX-2) may decrease the delayed cell death, and so this will contribute to decreased level of the secondary injury.
METHODS
The dorsal surface of the cord at the T9 level was subjected to weight drop impact using a 10 g rod. To block COX-2 activation, a selective COX-2 inhibitor (NS-398) was administered (5 mg/kg, i.p.) 15 min prior to SCI. The COX-1, COX-2, Caspase-3 and PGE2 expressions were measured by real time quantitative RT-PCR and fluorescence immunostaining.
RESULTS
Many activated caspase-3 positive cells were observed at 6 h and they increased until 72 h after SCI. The expression of COX-2 peaked at 6 h after SCI, while the COX-1 expression was unaffected. The principal cells that showed a COX-2 expression were the neurons and microglia. Pretreatment with NS-398 caused a significant decrease in the expression of prostaglandin E2 and activated caspase-3 positive cells after SCI.
CONCLUSION
These data suggest that COX-2 is one of the main factors related with the pathologic deficits from secondary SCI.

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