Annals of Coloproctology

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Malignant disease,Colorectal cancer

Upregulation of prostaglandin E₂ by inducible microsomal prostaglandin E synthase-1 in colon cancer: Young Hun Kim, Kyung Jong Kim; Ann Coloproctol. 2022;38(2):153-159. Published online August 31, 2021; DOI: https://doi.org/10.3393/ac.2021.00374.0053

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Purpose
Prostaglandin E₂ (PGE₂) is known to promote carcinogenesis and cancer progression in colon cancer. Enzymes involved in the metabolism of PGE₂ include cyclooxygenase (COX)-2, microsomal prostaglandin E synthase-1 (mPGES-1), and 15-prostaglandin dehydrogenase (15-PGDH). The current study aims to determine how PGE₂ is expressed by examining patients with colorectal cancer and evaluating colon cancer cells to gain insight into changes in relevant enzymes upon induction of PGE₂.
Methods
The concentration of PGE₂ was measured in tumor tissues and adjacent normal mucosal tissues of 26 patients with colon cancer. The expression of COX-1, COX-2, mPGES-1, and 15-PGDH proteins was measured. The concentration of PGE₂ in FET colon cancer cells was measured both in the initial status and after stimulation by tumor necrosis factor (TNF)-α. The expression levels of PGE₂-related enzymes were measured as well.
Results
There was no significant difference in the average concentration of PGE₂, which was measured at 453.1 pg/mL in cancer tissues and 401.2 pg/mL in normal mucosa. Among PGE₂-related enzymes, 15-PGDH was expressed at a lower level in tumor cells than in normal mucosa. In colon cancer cells, PGE₂ was found to be upregulated upon stimulation by TNF-α, which led to strong induction of mPGES-1 without any change in the expression of COX-2 among the PGE₂-related enzymes.
Conclusion
These results demonstrated that PGE₂ can be induced by stimuli such as TNF-α, and suggest that activation of mPGES-1 is more closely related than that of COX-2 in the induction of PGE₂ on colon cancer.

Citations

Citations to this article as recorded by

Stage-Dependent Role of Eicosanoids in Colorectal Cancer
Jakub Klekowski, Paulina Fortuna, Mariusz Chabowski, Łukasz Lewandowski, Wioleta Szewczak, Karolina Mosna, Gabriela Maciejewska, Marek Zawadzki, Małgorzata Krzystek-Korpacka, Mariusz Fleszar
International Journal of Molecular Sciences.2026; 27(4): 1641. CrossRef
5‐methyl‐2‐carboxamidepyrrole‐based novel dual mPGES‐1/sEH inhibitors as promising anticancer candidates
Ester Colarusso, Gianluigi Lauro, Marianna Potenza, Paola Galatello, Maria Luisa d'Aulisio Garigliota, Maria Grazia Ferraro, Marialuisa Piccolo, Maria Giovanna Chini, Carlo Irace, Pietro Campiglia, Robert Klaus Hoffstetter, Oliver Werz, Anna Ramunno, Gius
Archiv der Pharmazie.2025;[Epub] CrossRef
Furazanopyrazine-based novel promising anticancer agents interfering with the eicosanoid biosynthesis pathways by dual mPGES-1 and sEH inhibition
Gianluigi Lauro, Michela Aliberti, Mauro De Nisco, Silvana Pedatella, Giacomo Pepe, Manuela Giovanna Basilicata, Maria Giovanna Chini, Katrin Fischer, Robert K. Hofstetter, Oliver Werz, Maria Grazia Ferraro, Marialuisa Piccolo, Carlo Irace, Anella Saviano
European Journal of Medicinal Chemistry.2025; 289: 117402. CrossRef
Antioxidant, Antidiabetic, Anti-Obesity, and Anti-Inflammatory Activity of Tomato-Based Functional Snack Bars Enriched with Pea and RuBisCO Proteins
Elena Tomassi, Morena Gabriele, Agnese Sgalippa, Muhammed Rasim Gul, Ozan Tas, Mecit Halil Oztop, Laura Pucci
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The Role of Prostaglandins as Major Inflammatory Mediators in Colorectal Cancer
Mario Macia Guardado, Valentina Lutz, Markus Hengstschläger, Helmut Dolznig
International Journal of Molecular Sciences.2025; 26(24): 12191. CrossRef
Prostaglandin E2 in the Tumor Microenvironment, a Convoluted Affair Mediated by EP Receptors 2 and 4
Ana Santiso, Akos Heinemann, Julia Kargl
Pharmacological Reviews.2024; 76(3): 388. CrossRef
The calcium-sensing receptor modulates the prostaglandin E2 pathway in intestinal inflammation
Valeriya Gushchina, Nadja Kupper, Michael Schwarzkopf, Gitta Frisch, Karina Piatek, Cornelia Aigner, Alexandra Michel, Hemma Schueffl, Luca Iamartino, Taha Elajnaf, Teresa Manhardt, Andrea Vlasaty, Petra Heffeter, Marcella Bassetto, Enikö Kállay, Martin S
Frontiers in Pharmacology.2023;[Epub] CrossRef
Impact of Postoperative Naples Prognostic Score to Predict Survival in Patients with Stage II–III Colorectal Cancer
Su Hyeong Park, Hye Seung Woo, In Kyung Hong, Eun Jung Park
Cancers.2023; 15(20): 5098. CrossRef
Prostaglandin E2 Exposure Disrupts E-Cadherin/Caveolin-1-Mediated Tumor Suppression to Favor Caveolin-1-Enhanced Migration, Invasion, and Metastasis in Melanoma Models
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International Journal of Molecular Sciences.2023; 24(23): 16947. CrossRef
Inflammatory Response Markers as Predictors of Colorectal Cancer Prognosis
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The Ewha Medical Journal.2023;[Epub] CrossRef

Relation of the Expression of Cyclooxygenase-2 in Colorectal Adenomas and Adenocarcinomas to Angiogenesis and Prognosis: Yoon Dae Han, Young Ki Hong, Jung Gu Kang, Yoon Jung Choi, Chan Heun Park; J Korean Soc Coloproctol. 2010;26(5):339-346. Published online October 31, 2010; DOI: https://doi.org/10.3393/jksc.2010.26.5.339

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Abstract PDF

Purpose

Recent studies have shown that cyclooxygenase (COX)-2 may be involved in tumor growth, invasion and apoptosis in various carcinomas. Vascular endothelial growth factor (VEGF) has a potent angiogenic activity, and COX-2 promotes angiogenesis by modulating angiogenic factors, including VEGF. Endothelial growth factor receptor (EGFR) is considered as a factor of cell growth, maturation and cell death. The current study was designed to investigate the possible roles of COX-2 in colorectal tumor progression and angiogenesis.

Methods

Fifty colorectal adenomas and forty adenocarcinomas were investigated by using immunohistochemical staining for COX-2, VEGF and EGFR. The correlations of COX-2, VEGF and EGFR with the grade of dysplasia, the size of the adenoma, and various clinicopathologic factors were studied.

Results

The expressions of COX-2, VEGF and EGFR were each significantly correlated with carcinomatous transformation, and the expressions of COX-2 and VEGF were significantly correlated. COX-2 and EGFR showed correlations with adenomas rather than adenocarcinomas. However, no correlations of COX-2, VEGF and EGFR expression to other clinicopathologic factors, except tumor size in EGFR expression, were detected.

Conclusion

These results suggest that COX-2 may play an important role in carcinogenesis through interaction with VEGF and EGFR in human colorectal cancer.

Citations

Citations to this article as recorded by

In Vitro Anticancer Effects of Unitein and Deep Seawater Salt Minerals on HT-29 Human Colon Carcinoma Cells
Kyunghwa Lee, WoonSeo Song, YeonJun Lee, Yanni Pan, Suk-Chan Hahm, Kun-Young Park
Journal of the Korean Society of Food Science and Nutrition.2023; 52(1): 8. CrossRef
Ocoxin® oral solution slows down tumor growth in an experimental model of colorectal cancer metastasis to the liver in Balb/c mice
JOANA MÁRQUEZ, JORGE MENA, IERA HERNANDEZ-UNZUETA, AITOR BENEDICTO, EDUARDO SANZ, BEATRIZ ARTETA, ELVIRA OLASO
Oncology Reports.2016; 35(3): 1265. CrossRef
In vivo molecular imaging of epidermal growth factor receptor in patients with colorectal neoplasia using confocal laser endomicroscopy
Jun Liu, Xiuli Zuo, Changqing Li, Tao Yu, Xiaomeng Gu, Chengjun Zhou, Zhen Li, Martin Goetz, Ralf Kiesslich, Yanqing Li
Cancer Letters.2013; 330(2): 200. CrossRef
Imunoexpressão das proteínas COX-2, p53 e caspase-3 em adenoma colorretal e mucosa não neoplásica
Renan Brito Nogueira, Andréa Rodrigues Cordovil Pires, Thélia Maria Santos Soares, Simone Rabello de Souza Rodrigues, Mariane Antonieta Menino Campos, Giovanna Canato Toloi, Jaques Waisberg
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Oldhamianoside II, a New Triterpenoid Saponin, Prevents Tumor Growth via Inducing Cell Apoptosis and Inhibiting Angiogenesis
Feng-Ling Wang, Jing-Yong Sun, Yan Wang, Yan-Ling Mu, Yu-Ji Liang, Zhao-Zhong Chong, San-Hai Qin, Qing-Qiang Yao
Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics.2013; 20(8): 369. CrossRef
Effects of Resveratrol on Migration and Proliferation in HT-29 Colon Cancer Cells
Sol Hwa Lee, Song Yi Park, In-Seop Kim, Ock Jin Park, Young Min Kim
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Anti-Proliferative Effects of Selenium in HT-29 Colon Cancer Cells via Inhibition of Akt
Song-Yi Park, In-Seop Kim, Se-Hee Lee, Sol-Hwa Lee, Da-Woon Jung, Ock-Jin Park, Young-Min Kim
Journal of Life Science.2012; 22(1): 55. CrossRef

Clinical Significance of Cyclooxygenase-2 Expression in Colorectal Adenoma and Carcinoma.: Rhyou, Jai Hyun , Kim, Kwang Ho , Shim, Kang Sup , Koo, Hae Soo , Park, Eung Bum; J Korean Soc Coloproctol. 2000;16(6):351-355.

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Abstract PDF: PURPOSE
Interest is mounting in developing prevention strategies for patients at high risk of developing colorectal cancer. Recent epidemiological investigations indicate an inverse relationship between the intake of NSAIDs and colorectal cancer risk. Cyclooxygenase (COX) enzyme may be involved in the initiation and/or the promotion of carcinogenesis. A major action of NSAIDs is the inhibition of COX. We have studied the clinical significance of COX-2 expression in colorectal adenoma and carcinoma.
METHODS
We studied 19 patients with colorectal adenomas (15 males and 4 females: ages 30~73 years) and 20 patients with colorectal carcinoma (12 males and 8 females: ages 35~80 years). COX-2 status were determined by immunohistochemical methods using the mouse monocolnal antibody for COX-2 (Transduction Lab, USA) on paraffin sections.
RESULTS
Immunoreactive COX-2 were expressed in 9 patients (47%) of colorectal adenoma and 9 patients (45%) of colorectal carcinoma. 57% of villous adenoma and 42% of tubular adenoma were positive for COX-2 in colorectal adenoma (p=0.650). COX-2 were expressed in 12.5% of stage B and 73% of stage C of colorectal cancer (p=0.006). COX-2 expression did not relate with the size of adenoma and carcinoma.
CONCLUSIONS
The data suggest that COX-2 may be more expressed in villous adenoma and advanced carcinoma. Therefore, enhanced expression of COX-2 may play a role in the carcinogenesis of colorectal cancer.

Expression of Cyclooxygenase-2 and Inducible Nitric Oxide Synthase in Colorectal Cancer.: Yang, Keun Ho , Bae, Byung Noe , Kim, Jung Yeon , Kim, Ki Hwan , Han, Se hwan , Kim, Hong Joo , Kim, Young Duck , Kim, Hong Yong , Kim, Sung Jun; J Korean Soc Coloproctol. 2003;19(3):144-150.

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Abstract PDF: PURPOSE
Recently, it has been recognized that both cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) produce important endogeneous factors of human tumor progression. The aims of this study is to investigate the correlation between the expression of COX-2 and iNOS and to assess the clinicopathological significance of COX-2 and iNOS expression in patients with colorectal cancer.
METHODS
One hundred and five patients, who underwent curative resection of colorectal cancer from 1994 to 1997 were analyzed retrospectively. The monoclonal antibody to the COX-2 and iNOS were used for the immunohistochemical analysis.
RESULTS
In 105 patients the COX-2 and iNOS positive rate were 86.7% and 69.5% respectively. There was significant correlation between COX-2 and iNOS expression (r= 0.378, P<0.01), that is, the lesions which expressed high level of COX-2 also expressed iNOS highly. The proliferation index (Ki-67 labeling index) was correlated with iNOS (P=0.013), and the microscopic differentiation with COX-2 (P=0.004). However, the expression of COX-2 and iNOS proteins did not correlate with any other clinicopathological parameters including patient survival.
CONCLUSIONS
Although the pattern of positive expression was similar in both enzymes, the expression of both enzymes was not related to prognosis in patients with colorectal cancer. But COX-2 and iNOS seems to have a role not only in carcinogenesis but also tumor cells proliferation. To evaluate the exact role of these enzymes, further studies of the apoptosis and cancer metastasis and of links between the cancer related factors of COX-2 and iNOS are warranted.

Review

Colorectal Cancer and Prostaglandin.: Chang, Woong Ki; J Korean Soc Coloproctol. 2003;19(1):52-59.

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Abstract PDF: The possibility for cyclooxygenase (COX) inhibitors in colorectal cancer prevention and theraphy is evident from epidemiologic data (reduction of colorectal cancer in nonsteroidal anti-inflammatory drugs (NSAIDs) users), animal experiments (nude mouse xenograft tumor reduced by NSAIDs or reduction of colorectal cancer in APCmin mouse and azoxymethane treated rat by using NSAIDs), and molecular genetics. Among two variant COX, inducible COX-2 enzyme is more involved in tumorigenesis than constitutive COX-1 enzyme and molecular method have given us insight into the mechanism of colorectal cancer development by COX-2 such as, apoptosis, angiogenesis, invasiveness, and immune modulation. Based on that COX-2 is involved in tumor promotion during colorectal cancer progress, a large number of prevention and treatment trials of colorectal cancer have been started. And many trials to elucidate the function of prostaglandin produced by COX-2 are now in progress.

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