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Kelly P, Lauwers GY. Polyps and tumour‐like lesions of the stomach. MORSON AND DAWSON'S GASTROINTESTINAL PATHOLOGY 2024:195-226. [DOI: 10.1002/9781119423195.ch12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Ma B, Huang XT, Zou GJ, Hou WY, Du XH. Relationship between Ki-67 and CD44 expression and microvascular formation in gastric stromal tumor tissues. World J Clin Cases 2022; 10:469-476. [PMID: 35097071 PMCID: PMC8771385 DOI: 10.12998/wjcc.v10.i2.469] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Revised: 10/08/2021] [Accepted: 11/29/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND A gastric stromal tumor (GST) is a mesenchymal tumor that occurs in the gastrointestinal tract; its biological characteristics are highly complex. Clinically, the severity of a GST is often evaluated by factors such as risk classification, tumor size, and mitotic figures. However, these indicators are not very accurate. Even patients classified as low risk are also at risk of metastasis and recurrence. Therefore, more accurate and objective clinical biological behavior evaluations are urgently needed.
AIM To determine the relationship between Ki-67 and CD44 expression in GSTs and microvessel formation and prognosis.
METHODS Eighty-six GST tissue specimens from our hospital were selected for this study. The immunohistochemical staining technique was used to detect Ki-67, CD44, and microvessel density (MVD) in the collected samples to analyze the different risk grades and mitotic figures. In addition, this approach was used to determine the differences in the expression of Ki-67 and CD44 in GST tissues with varying lesion diameters.
RESULTS In GSTs with positive expression of the Ki-67 protein, the proportions of patients with medium-to-high risk and more than five mitotic counts were 24.07% and 38.89%, respectively. In GSTs with positive expression of the CD44 protein, the proportions of patients with medium-to-high risk and more than five mitotic counts were 23.73% and 38.98%, respectively. In GSTs with negative expression of the Ki-67 protein, these values were relatively high (3.70% and 11.11%, respectively). The MVD in GSTs with positive and negative expression of the CD44 protein was 15.92 ± 2.94 and 13.86 ± 2.98/Hp, respectively; the difference between the two groups was significant (P < 0.05).
CONCLUSION Ki-67 and CD44 expression in GSTs is correlated with the grade of tumor risk and mitotic figures. CD44 expression is correlated with microvessel formation in tumor tissues.
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Affiliation(s)
- Bing Ma
- Department of General Surgery, The PLA General Hospital, Beijing 100853, China
| | - Xiao-Tian Huang
- Department of General Surgery, The PLA General Hospital, Beijing 100853, China
| | - Gui-Jun Zou
- Department of General Surgery, The PLA General Hospital, Beijing 100853, China
| | - Wen-Yu Hou
- Department of General Surgery, The PLA General Hospital, Beijing 100853, China
| | - Xiao-Hui Du
- Department of General Surgery, The PLA General Hospital, Beijing 100853, China
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Kim K, Clauditz TS, Lee JH, Lauwers GY. Polyps of the Stomach. GASTROINTESTINAL PATHOLOGY 2021:99-123. [DOI: 10.1002/9781119073048.ch5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Gosepath J, Brieger J, Mann WJ. New Immunohistologic Findings on the Differential Role of Cyclooxygenase 1 and Cyclooxygenase 2 in Nasal Polyposis. ACTA ACUST UNITED AC 2018. [DOI: 10.1177/194589240501900201] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Background Cyclooxygenase 1 (Cox-1) plays a key role in arachidonic acid metabolism and in the pathophysiology and immunology of nasal polyposis in patients suffering from aspirin intolerance. We hypothesize that Cox-2 also might be relevant in the etiology of nasal polyps of aspirin-tolerant patients by their effects on inflammatory mediators as well as on microvascular permeability. Methods Fifty-two surgical specimens were immunohistochemically labeled for Cox-1 and Cox-2. Specimens were taken from chronically inflamed mucosa (n = 19) and from nasal polyps (n = 19) during endonasal sinus surgery. Controls were obtained from healthy nasal respiratory mucosa (n = 14), harvested during turbinate surgery in patients with nasal obstruction without inflammatory disease. Staining intensities were semiquantitatively assessed and statistically analyzed. Results In chronically inflamed tissue the expression of Cox-1 and Cox-2 was strongly labeled. However, in nasal polyps the staining pattern of Cox-1 was similar, but Cox-2 expression in epithelial cells was significantly less than in inflamed, nonpolypous specimens. Conclusion These data suggest that while Cox-1 is strongly up-regulated, Cox-2 expression is significantly lower in epithelial cells of nasal polyps than in those of chronic sinusitis without polyps. The relevance of this finding has to be discussed with respect to the regulatory function of Cox on the inflammatory reaction in nasal respiratory mucosa and its hypothetical role in alterations of capillary permeability via vascular permeability factor/vascular endothelial growth factor.
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Affiliation(s)
- Jan Gosepath
- Department of Otolaryngology, Head and Neck Surgery, University of Mainz, School of Medicine, Mainz, Germany
| | - Juergen Brieger
- Department of Otolaryngology, Head and Neck Surgery, University of Mainz, School of Medicine, Mainz, Germany
| | - Wolf J. Mann
- Department of Otolaryngology, Head and Neck Surgery, University of Mainz, School of Medicine, Mainz, Germany
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Gosepath J, Brieger J, Lehr HA, Mann WJ. Expression, Localization, and Significance of Vascular Permeability/Vascular Endothelial Growth Factor in Nasal Polyps. ACTA ACUST UNITED AC 2018. [DOI: 10.1177/194589240501900102] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Background The exact etiologic mechanisms leading to the formation of nasal polyps have remained largely obscure. A key phenomenon of this specific type of chronic inflammatory disease in nasal respiratory mucosa is remarkable edema. Vascular permeability/vascular endothelial growth factor (VPF/VEGF) plays an important role in inducing angiogenesis and modulating capillary permeability. Objective To study the expression and localization of VPF/VEGF as a putative key factor in nasal polyp development. Methods Specimens of nasal polyps (n = 12) were harvested during endonasal sinus surgery in patients with polypous chronic rhinosinusitis. Specimens of healthy nasal respiratory mucosa (n = 12) served as controls and were obtained from inferior turbinates of patients undergoing surgery for nasal obstruction without signs and symptoms of inflammatory disease. Frozen sections were immunohistochemically stained for VPF/VEGF and quantitatively analyzed, using computer-based image analysis. Results The expression of VPF/VEGF in specimens of nasal polyps was significantly stronger than in specimens of healthy nasal mucosa of controls. VPF/VEGF in polypous tissue was mainly localized in vascular endothelial cells, in basal membranes and perivascular spaces, and in epithelial cells. Conclusion The markedly increased expression in nasal polyps as opposed to healthy nasal mucosa suggests that VPF/VEGF may play a significant role in both the formation of nasal polyps and in the induction of heavy tissue edema. This finding is discussed with respect to the differential expression of cyclooxygenase (COX) isoenzymes-1 and -2 (COX-1 and COX-2) in nasal polyps.
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Affiliation(s)
- Jan Gosepath
- Department of Otolaryngology, Head and Neck Surgery, University of Mainz, School of Medicine, Mainz, Germany
| | - Juergen Brieger
- Department of Otolaryngology, Head and Neck Surgery, University of Mainz, School of Medicine, Mainz, Germany
| | - Hans Anton Lehr
- Institute of Pathology, University of Mainz, School of Medicine, Mainz, Germany
| | - Wolf J. Mann
- Department of Otolaryngology, Head and Neck Surgery, University of Mainz, School of Medicine, Mainz, Germany
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Parikh M, Kelley B, Rendon G, Abraham B. Intermittent gastric outlet obstruction caused by a prolapsing antral gastric polyp. World J Gastrointest Oncol 2010; 2:242-6. [PMID: 21160624 PMCID: PMC2998838 DOI: 10.4251/wjgo.v2.i5.242] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2009] [Revised: 11/30/2009] [Accepted: 12/07/2009] [Indexed: 02/05/2023] Open
Abstract
Most gastric polyps have an asymptomatic presentation and are an incidental finding on upper endoscopy. Symptomatic presentations can range from an ulcerated polyp leading to anemia and occult bleed to complete gastric outlet obstruction. We report a case of an 89-year-old woman who presented with postprandial nausea and early satiety. Her upper endoscopy revealed a 2 cm pedunculated hyperplastic polyp arising from the antrum of the stomach which was seen prolapsing into the pylorus causing intermittent gastric outlet obstruction. In the present report, we statistically analyzed 39 prolapsing gastric polyps previously reported in the English literature and demonstrate the current utility of monopolar snare polypectomy in establishing a histological diagnosis while offering simultaneous treatment. Additionally, we review the literature for the management of all hyperplastic gastric polyps in relation to advancements in digestive endoscopy.
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Affiliation(s)
- Mehul Parikh
- Mehul Parikh, Brian Kelley, Gabriel Rendon, Bincy Abraham, Department of Internal Medicine, Baylor College of Medicine, Houston, TX 77030, United States
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Kim K, Jeon YT, Park IA, Kim JW, Park NH, Kang SB, Lee HP, Song YS. Cyclooxygenase-2 expression in cervical intraepithelial neoplasia. Ann N Y Acad Sci 2009; 1171:111-5. [PMID: 19723044 DOI: 10.1111/j.1749-6632.2009.04724.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
To evaluate the role of cyclooxygenase (COX)-2 during cervical carcinogenesis, we investigated COX-2 expression in the dysplastic epithelium and stromal cells of cervical intraepithelial neoplasia (CIN). Immunohistochemical analysis with COX-2 antibody was performed on 148 paraffin-embedded tissue specimens of patients who were diagnosed as CIN in our institute. COX-2 expression was evaluated separately in the dysplastic epithelium and stromal cells of CIN. The relationships between COX-2 expression and clinicopathologic variables were examined. For the dysplastic epithelium, COX-2 expression was negative in 137 (92.6%) and positive in 11 (7.4%) specimens. For the stromal cells, COX-2 expression was negative in all specimens. The COX-2 expression in dysplastic epithelium was higher in older (P= 0.038) or postmenopausal (P= 0.025) women. In conclusion, COX-2 expression was observed only in the dysplastic epithelium but not in the stromal cells of CIN. The COX-2 expression in dysplastic epithelium was associated with age and menopausal status.
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Affiliation(s)
- Kidong Kim
- Department of Obstetrics and Gynecology, Korea Institute of Radiological & Medical Sciences, Seoul, Korea
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Dursun P, Yuce K, Usubutun A, Ayhan A. Cyclooxygenase-2 expression in cervical intraepithelial neoplasia III and squamous cell cervical carcinoma, and its correlation with clinicopathologic variables. Int J Gynecol Cancer 2007; 17:164-73. [PMID: 17291249 DOI: 10.1111/j.1525-1438.2007.00798.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
Abstract
The objective of the study was to compare cyclooxygenase-2 (COX-2) expression in cervical intraepithelial neoplasia III (CIN III) and squamous cell carcinoma (SCC) of the cervix, and its correlation with clinicopathologic factors of SCC with a review of the available literature. This study included 25 patients with CIN III and 67 patients with stage I-IIa SCC. All patients in the SCC group were treated with radical hysterectomy plus pelvic and para-aortic lymphadenectomy and postoperative chemoradiotherapy based on their histopathologic risk factors. Immunohistochemical analysis was performed on paraffin-embedded sections with COX-2 antibody. COX-2 expression in the SCC group was significantly higher than in the CIN III group (55.2% [37/67] vs 24% [6/25]; P= 0.008). Significantly higher expression of COX-2 was observed in patients with lymphovascular space invasion (LVSI) compared to patients without LVSI (61.9% [34/55] vs 33.3% [3/9]; P= 0.02). Additionally, patients with tumor sizes >4 cm had significantly higher COX-2 expression than patients with tumor sizes <4 cm (65.9% [27/41] vs 39% [10/26] P= 0.028). There was no significant relationship with respect to COX-2 expression and parametrial involvement, lymph node metastasis, recurrences, and survival. In multivariate analysis, LVSI was the only statistically significant determinant for COX-2 expression (P= 0.024; OR = 2.35; 95% CI = 1.1-4.9). Our results and a review of the literature both suggest that COX-2 expression may have a role in the development and progression of CIN III and it is related to some clinicopathologic variables of cervical carcinoma. Further studies are needed to clarify the role of COX-2 inhibitors in the management of CIN and SCC.
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Affiliation(s)
- P Dursun
- Department of Obstetrics and Gynecology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
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Gosepath J, Mann WJ. Current concepts in therapy of chronic rhinosinusitis and nasal polyposis. ORL J Otorhinolaryngol Relat Spec 2006; 67:125-36. [PMID: 15942266 DOI: 10.1159/000086075] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2004] [Accepted: 07/01/2004] [Indexed: 01/02/2023]
Abstract
The exact pathophysiological mechanisms leading to chronic rhinosinusitis (CRS) still to a large extent remain obscure. However, recently there has been some progress in elucidating the etiology of nasal polyposis, especially regarding tissue eosinophilia as well as the role of aspirin intolerance and eicosanoid mediators. Endonasal sinus surgery has evolved to be the treatment of choice in CRS and nasal polyposis in all cases where conservative treatment has failed or resulted in only a partial or temporary relief. Today, state of the art in surgical technique includes the ability to combine microscopic and endoscopic procedures. Regardless of technical advances like powered instrumentation or computer-aided surgery, in a modern protocol, surgical therapy can offer only one option within a complex and individually tailored therapeutical concept. This review discusses current concepts and new developments in the diagnosis and treatment of CRS and nasal polyposis.
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Affiliation(s)
- Jan Gosepath
- Department of Otolaryngology, Head and Neck Surgery, School of Medicine, University of Mainz, Mainz, Germany.
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Kanda N, Seno H, Kawada M, Sawabu T, Uenoyoma Y, Nakajima T, Konda Y, Fukui H, Takeuchi T, Chiba T. Involvement of cyclooxygenase-2 in gastric mucosal hypertrophy in gastrin transgenic mice. Am J Physiol Gastrointest Liver Physiol 2006; 290:G519-27. [PMID: 16254046 DOI: 10.1152/ajpgi.00113.2005] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Gastrin promotes gastric mucosal growth, and hypergastrinemia induces gastric mucosal hypertrophy. Recently, it has been reported that gastrin induces cyclooxygenase-2 (COX-2) in human gastric and colorectal cancer cell lines. However, whether COX-2 is involved in gastrin-induced gastric mucosal growth in vivo is unknown. We investigated the role of COX-2 in gastrin-induced gastric mucosal hypertrophy using gastrin transgenic mice. Hypergastrinemic mice [mice with mutated gastrin under the control of the beta-actin promoter (ACT-GAS mice)] received the COX-2 inhibitor celecoxib (0, 200, or 500 mg/kg of diet) from 5 wk of age and were killed at 16 or 24 wk. Some ACT-GAS mice received celecoxib from 16 wk and were killed at 24 wk. Eighty-week-old ACT-GAS mice without celecoxib treatment were also examined. The thickness of the gastric mucosa, cell populations, COX-2 expression, and PGE(2) levels were evaluated. All ACT-GAS mice showed gastric mucosal hypertrophy, and four of six 80-wk-old ACT-GAS mice developed gastric cancer. COX-2 was expressed in interstitial cells of the hypertrophic gastric mucosa and gastric cancers. Moreover, PGE(2) levels in the gastric mucosa of ACT-GAS mice were significantly higher than those of normal mice. With treatment with celecoxib, PGE(2) levels, the gastric mucosal thickness, and the number of total gastric cells per gastric gland of ACT-GAS mice were significantly decreased. The decrease in gastric mucosal thickness was caused by a reduction of foveolar hyperplasia. The thickness of glandules and the number of Ki67-positive cells were not significantly changed. In conclusion, COX-2 contributes to gastrin-induced mucosal hypertrophy of the stomach.
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Affiliation(s)
- Naoki Kanda
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Shogoin-Kawara-cho 54, Sakyo-ku, Kyoto 606-8507, Japan
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Uenoyama Y, Seno H, Fukuda A, Sekikawa A, Nanakin A, Sawabu T, Kawada M, Kanda N, Suzuki K, Yada N, Fukui H, Chiba T. Hypoxia induced by benign intestinal epithelial cells is associated with cyclooxygenase-2 expression in stromal cells through AP-1-dependent pathway. Oncogene 2006; 25:3277-85. [PMID: 16407821 DOI: 10.1038/sj.onc.1209359] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Cyclooxygenase-2 (COX-2) plays important roles in tumor development. Especially in the early-stage colorectal tumors, COX-2 expression is often observed in the tumor stroma. However, the mechanism regulating such stromal expression of COX-2 remains unknown. In the present study, we simulated the indirect interaction between epithelial cells and stromal cells in the process of colorectal tumor development using an in vitro co-culture model in which NIH3T3 fibroblasts were co-cultured with 'sparsely' or 'densely' populated intestinal epithelial cells, Intestine-407 as a model of premalignant or benign intestinal epithelial cells, and DLD-1 and Caco-2 as models of malignant epithelial cells. COX-2 expression in NIH3T3 fibroblasts was upregulated when co-cultured with the 'dense' epithelial cells regardless of their character. Interestingly, there was pericellular hypoxia in the vicinity of NIH3T3 fibroblasts when co-cultured with 'dense' epithelial cells, and the recovery of the partial pressure of oxygen level resulted in the reduction of enhanced COX-2 expression only in NIH3T3 fibroblasts co-cultured with 'dense' Intestine-407 cells. Furthermore, COX-2 expression was also reduced by the inhibition of transcription factor AP-1. Thus, pericellular hypoxia of the stromal cells caused by densely populated epithelial cells may be one of the potent COX-2 enhancers before completion of malignant transformation during intestinal tumor development.
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Affiliation(s)
- Y Uenoyama
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
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Park JH, Kang KH, Kim SH, Lee JH, Cho CM, Kweon YO, Kim SK, Choi YH, Bae HI, Kim MS. Expression of Cyclooxygenase-2 and Bcl-2 in human gastric adenomas. Korean J Intern Med 2005; 20:198-204. [PMID: 16295777 PMCID: PMC3891153 DOI: 10.3904/kjim.2005.20.3.198] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
BACKGROUND Cyclooxygenase (COX)-2 is the rate-limiting enzyme in prostaglandin synthesis. An increased expression has been implicated in the development and progression of human gastric cancers and colorectal adenomas and cancers. This study aimed to determine the involvement and association of COX-2 and Bcl-2 in precancerous gastric adenomas. METHODS Seventy-nine gastric polyps were obtained by endoscopic mucosal resection or polypectomy from January, 2000 to July, 2003. Immunohistochemical expression of COX-2 and Bcl-2 was observed, and their relationships with various clinicopathological factors were analyzed. RESULTS Histologically, 13 hyperplastic polyps and 66 tubular adenomas, of which 17 showed high-grade dysplasia, were observed. Increased COX-2 expression was observed in low-grade and high-grade tubular adenomas compared to hyperplastic polyps (p=0.004 and p=0.001, respectively). COX-2 expression was significantly higher in larger (>1 cm) compared with smaller (<1 cm) tubular adenomas (o=0.034), but no relation was observed in hyperplastic polyps. While Bcl-2 expression differed significantly according to histology, increased Bcl-2 expression was observed especially in COX-2 positive low-grade tubular adenomas. CONCLUSION COX-2 expression increased in a size-dependent manner in tubular adenomas, suggesting a role in polyp growth. The increased expression of Bcl-2 in tubular adenomas, especially in COX-2 positive tubular adenomas, suggests that COX-2 action may be related to Bcl-2 expression.
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Affiliation(s)
- Jee Hyun Park
- Department of Internal Medicine, Kumi Cha Medical Center, Gumisi, Kyungsangbukdo, Korea.
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Yasuda H, Yamada M, Endo Y, Inoue K, Yoshiba M. Elevated cyclooxygenase-2 expression in patients with early gastric cancer in the gastric pylorus. J Gastroenterol 2005; 40:690-697. [PMID: 16082585 DOI: 10.1007/s00535-005-1612-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2004] [Accepted: 03/01/2005] [Indexed: 02/04/2023]
Abstract
BACKGROUND Duodenogastric reflux after surgery increases the risk of gastric carcinoma. To determine whether bile reflux influences the development of gastric cancer in patients who have not had surgery, we compared cyclooxygenase-2 (COX-2) immunoreactivity in early gastric cancer originating from the gastric pylorus and that originating from other locations. We also examined the effects of bile acids on the expression and activity of COX-2 in gastric cells in vitro. METHODS Tumor sections from 79 patients who underwent endoscopic mucosal resection for early intestinal-type gastric carcinoma were stained using a COX-2-specific monoclonal antibody. Immunoblotting of COX-2 was used to assess the effects of bile acids on COX-2 expression and activity in human gastric cell lines. RESULTS Among the 79 early gastric cancer lesions studied, 13 (16%) arose in the gastric pylorus. In this group, COX-2 immunoreactivity was negative to weak in 38% (5 of 13 lesions) and moderate to strong in 62% (8 of 13 lesions). In the control group, COX-2 immunoreactivity was negative to weak in 70% (46 of 66 lesions) and moderate to strong in 30% (20 of 66 lesions). COX-2 expression was significantly elevated in early gastric cancer located in the gastric pylorus, compared with that in the other locations. In human gastric cell lines, bile acids induced COX-2 expression, mediated by the ERK 1/2 mitogen-activated protein kinase pathway. CONCLUSIONS COX-2 expression is elevated in early gastric cancer of the gastric pylorus, a common site of gastric cancer. Bile acids induced COX-2 expression in human gastric cell lines, suggesting a role of bile reflux in gastric carcinogenesis.
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Affiliation(s)
- Hiroshi Yasuda
- Division of Gastroenterology, Showa University Fujigaoka Hospital, 1-30 Fujigaoka, Yokohama, 227-8501, Japan
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Sun BC, Zhao XL, Zhang SW, Liu YX, Wang L, Wang X. Sulindac induces apoptosis and protects against colon carcinoma in mice. World J Gastroenterol 2005; 11:2822-6. [PMID: 15884131 PMCID: PMC4305925 DOI: 10.3748/wjg.v11.i18.2822] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To study the effect of sulindac on colon cancer induction in mice.
METHODS: The chemo-preventive action of 80 ppm sulindac fed during initiation and post-initiation and 100 ppm sulindac fed during progressive stages of induction of colon carcinogenesis in mice was investigated using 1,2-dimethylhydrazine (DMH). Using the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) technique and PCNA immunohistochemical staining, we observed the apoptotic and proliferative cell density changes at different carcinogenic stages and the effect of sulindac on these two phenomena.
RESULTS: Dietary sulindac significantly inhibited the incidence of colonic neoplasmas in mice. Compared with the control group, feeding sulindac during initiation and post-initiation stages inhibited the incidence by 46.7-50.4%, and feeding sulindac during progressive stages inhibited the incidence by 41.1%. Animals that were fed sulindac showed less serious pathological changes than those that were fed the control diet (P<0.01, H = 33.35). There was no difference in the density of proliferating cells among those groups which were or were not fed sulindac. In the same period, feeding sulindac resulted in a higher density of apoptotic cells than feeding control diet.
CONCLUSION: Sulindac has an anti-carcinogenic function in mice. Its effect on preventing colon carcinogenesis is better than its effect on treating established tumors. By inducing apoptosis, sulindac inhibited the development of colon cancer and delayed canceration. Sulindac has no effect on proliferation. The anti-carcinogenic properties of sulindac are most effective in the moderate and severe stages of dysplasia and canceration.
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Affiliation(s)
- Bao-Cun Sun
- Department of Pathology, Tianjin Medical University, Tianjin 300070, China.
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Brazowski E, Rozen P, Misonzhnick-Bedny F, Gitstein G. Characteristics of familial juvenile polyps expressing cyclooxygenase-2. Am J Gastroenterol 2005; 100:130-8. [PMID: 15654792 DOI: 10.1111/j.1572-0241.2005.40775.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Familial juvenile polyposis (FJP) is a dominant genetic disorder characterized by colorectal, gastric, and small bowel juvenile polyps, and high risk for gastrointestinal cancer. Patients are treated by repeated endoscopic polypectomies and elective surgery. We determined the characteristics of FJP polyps expressing cyclooxygenase-2 (COX-2). METHODS A total of 115 colorectal and 6 gastric polyps were available from 17 FJP patients. Comparison tissues were 18 sporadic juvenile colorectal polyps, 6 gastric hyperplastic polyps, 9 normal colons, and 3 colorectal cancers (CRCs). Histology sections were classified and stained for COX-2. The polyps' epithelium and stroma and comparison tissues were quantified for COX-2 by: area of staining (0-3) x intensity (0-3). Epithelial and stromal scores (0-9) and total scores (0-18) were evaluated in relationship to patient's age, polyp site, size, dysplasia, and stromal cellularity. RESULTS Colonic FJP polyps mean total COX-2 score was 10.3 +/- 6.0, and that of sporadic juvenile polyps 3.6 +/- 2.2 (p < 0.01), and in contrast to the latter, FJP COX-2 scores increased significantly (p < 0.01) with polyp size. Linear regression analysis showed significant associations of COX-2 in FJP polyps with dysplasia (p < 0.01), stromal cellularity (p < 0.01), size (> or =1.5 cm) (p= 0.02), and site (right colon) (p= 0.01), and not with age. COX-2 total scores of gastric FJP polyps and hyperplastic polyps were similar. CONCLUSIONS Expression of COX-2 in FJP polyps and its association with size and dysplasia suggest that, in these patients, chemoprevention with selective COX-2 inhibitors might be a useful adjunct therapy to colonoscopic polypectomy.
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Affiliation(s)
- Eli Brazowski
- Departments of Pathology & Gastroenterology, Tel Aviv Medical Center & Tel Aviv University, 6 Weizmann Street, Tel Aviv 64239, Israel
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Brazowski E, Misonzhnick-Bedny F, Rozen P. Cyclooxygenase-2 expression in the hereditary mixed polyposis syndrome. Dig Dis Sci 2004; 49:1906-11. [PMID: 15628724 DOI: 10.1007/s10620-004-9591-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Hereditary mixed polyposis syndrome (HMPS), characterized by hyperplastic, juvenile, admixed, serrated adenomas and eventually colorectal cancer, is managed by repeated polypectomy and surgery. We determined if HMPS polyps express cyclooxygenase-2 (COX-2). Nineteen recent HMPS polyps, from five family members, were stained for COX-2. Polyps' epithelium and stroma and comparison tissues (normal colonic mucosa [9], sporadic juvenile polyps [18], colorectal cancers [3]) were quantified for COX-2 by: area of staining (0-3) x intensity (0-3). Epithelial, stromal, and total scores were evaluated in relationship to histology and dysplasia. HMPS polyps COX-2 mean epithelial (5.0+/-3.0), stromal (6.9+/-1.9), and total (11.8+/-4.6) scores were significantly higher (P < 0.01) than sporadic juvenile polyps (0.6+/-0.7, 3.1+/-2.2, and 3.6+/- 2.2 respectively), while colorectal cancer scored 9, 9, and 18. There was a positive association (P < 0.01) among histology, degree of dysplasia, and COX-2 expression. COX-2 expression in HMPS polyps and its association with dysplasia suggest that chemoprevention might be a useful adjunct therapy.
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Affiliation(s)
- Eli Brazowski
- Department of Pathology, Tel Aviv Medical Center, Tel Aviv, Israel
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