Relation of the Expression of Cyclooxygenase-2 in Colorectal Adenomas and Adenocarcinomas to Angiogenesis and Prognosis

Han, Young Mi; Hong, Young Ki; Kang, Jung Gu; Choi, Yoon Jung; Park, Chan Heun

doi:10.3393/jksc.2010.26.5.339

Cited by 11 publications

(5 citation statements)

References 26 publications

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“…Wasilewicz et al showed that the expression of COX-2 in colon polyps is associated with polyp length (20). In addition, Han et al found higher COX-2 expression in patients with colorectal cancer who also had polyps, but consistent with our results, there was no correlation between the clinicopathological variables and COX-2 levels (21). Here we measured, for the first time, plasma COX-2 protein levels in control, polyp, and cancer groups; however, no significant differences were found.…”

Section: Discussionsupporting

confidence: 84%

The Importance of Fecal and Plasma CEA, COX-2, MMP-7, and TIMP-1 in the Diagnosis of Colorectal Cancer

Kiyak

Keles

Bengi

et al. 2018

J Basic Clin Health Sci

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Purpose: Colorectal cancer (CRC) is one of the most common and death related cancers in the world. Therefore, the early diagnosis of CRC remains with a great importance to prevent its further progression and increase survival rates. Colonoscopy and pathological examinations which are invasive and painful procedures, are needed to make a definitive diagnosis of CRC. The carcinoembryonic antigen (CEA) is particularly used for postoperative follow-up of CRC patients. The imbalance between matrix metalloproteinases (MMPs) and their tissue inhibitors of metalloproteinases (TIMPs) leads to degradation of extracellular matrix which is the most important step in invasion and metastasis. It was also observed that cyclooxygenase-2 (COX-2) has crucial roles in the development and progression of colorectal cancer. The purpose of our study is to detect fecal and plasma MMP-7, COX-2, TIMP-1, and CEA protein levels in patients with colorectal cancer, colorectal polyps, and healthy individuals, and assess their association with each other and with clinicopathological variables. We also aimed to evaluate plasma and fecal MMP-7, COX-2, TIMP-1, and CEA protein levels as potential diagnostic markers in colorectal carcinoma.Methods: Plasma and fecal samples were taken from patients with fifteen colorectal cancers, twenty-six colorectal polyps, and thirty-three healthy volunteers. Protein extraction was carried out from fecal samples. Plasma and fecal MMP-7, TIMP-1, and COX-2 protein levels were determined by ELISA whereas plasma and fecal CEA protein levels were detected with CEIA.Results: Plasma and fecal CEA levels were significantly higher in CRC than the control. In addition, plasma TIMP-1 and plasma CEA levels were significantly elevated in cancer according to polyp group. We also detected decreased plasma MMP-7 levels in polyps compared to control group. Positive correlations were observed among plasma COX-2 and TIMP-1 levels (r=0.571), fecal COX-2 and CEA levels (r=0.764) in CRC. However, no association was found between biochemical parameters and clinicopathological variables. ROC analysis for discriminating CRC from healthy controls showed that area under curves (AUC) for fecal and plasma CEA levels were 0.763 and 0.692, respectively. Plasma CEA (AUC=0.735), plasma TIMP-1 (AUC=0.706), and their combination (AUC=0.760) exhibited significant diagnostic performances to differentiate CRC from polyp. In discrimination colorectal polyps from healthy tissues, MMP-7 showed the highest AUC value (0.667). Conclusion:Here we suggested that plasma and fecal CEA protein levels may be potential predictive noninvasive markers for diagnosis of colorectal adenocarcinoma. In addition, plasma CEA and TIMP-1 are also valuable biomarker candidates in differentiating colorectal cancer from colorectal polyps.

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Section: Discussionsupporting

confidence: 84%

The Importance of Fecal and Plasma CEA, COX-2, MMP-7, and TIMP-1 in the Diagnosis of Colorectal Cancer

Kiyak

Keles

Bengi

et al. 2018

J Basic Clin Health Sci

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“…Among them, TNFα or IL-1β induce the expression of growth factors, stimulate epithelial tumor motility and tumor angiogenesis ( 30 , 31 ). Another proinflammatory molecule commonly upregulated in colon cancer, COX-2, has been implicated in the growth and progression of colorectal cancer via multiple pathways ( 32 – 34 ) including the acquisition of resistance to apoptosis and promoting angiogenesis through VEGF production ( 35 , 36 ). Moreover, a decrease in COX-2 expression at RNA levels in total liver caused by OOS administration might be related to a reduction in VEGF levels ( 36 ).…”

Section: Discussionmentioning

confidence: 99%

Ocoxin® oral solution slows down tumor growth in an experimental model of colorectal cancer metastasis to the liver in Balb/c mice

et al. 2015

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Liver metastatic disease is the main cause of death in colorectal cancer (CRC) patients. During metastatic spread of the disease an imbalance in the oxidative stress and inflammation plays a crucial role in tumor progression. In order to improve the efficacy of current therapies, new complementary therapeutic approaches are being analyzed including biologically active compounds with low side effects. The anti-inflammatory and anti-oxidant properties of Ocoxin® oral solution (OOS) prompt us to analyze its effect on the metastatic development of CRC to the liver. First, in vitro effect of OOS in tumor cell viability and migration was analyzed. Second, in vivo effect of different dosage patterns and concentrations in the development of hepatic metastasis was analyzed by intrasplenic inoculation of C26 colon carcinoma cells in Balb/c mice. Third, the expression of alpha smooth muscle actin, caspase-3 and Ki-67 expression was quantified by immunohistochemistry, then gene expression levels of inflammatory factors were measured by quantitative RT-PCR. According to our results, OOS reduced tumor cell viability and migration in vitro. Moreover, in vivo daily administration of OOS from the 7th day after tumor cell inoculation decreased the total area and size of metastatic foci in the liver. Furthermore, cell proliferation and fibroblast recruitment was decreased in tumor foci while a higher number of apoptotic cells were observed. Finally, RNA levels for the inflammatory mediators COX-2, IFNγ, IL1β, IL6 and TNFα were reduced in total liver. In conclusion, OOS reduced the metastatic development of colorectal cancer to the liver by increasing apoptosis, and decreasing tumor cell proliferation and fibroblast recruitment in the tumor foci, as well as the expression of inflammatory mediators in total liver. These results point out OOS as a potential supplement to be applied as complementary therapy for the treatment of liver metastasis from colorectal cancer.

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“…Han et al ( 30 ) correlated the expression of COX-2 with the tumor size in 50 colorectal adenomas and 40 carcinomas and did not determine a significant relationship. In the present study, the association between the expression of COX-2 and the degree of dysplasia, size, and histological type of the adenomas was not significant.…”

Section: Discussionmentioning

confidence: 99%

Imunoexpressão das proteínas COX-2, p53 e caspase-3 em adenoma colorretal e mucosa não neoplásica

Nogueira

Pires

Soares³

et al. 2013

Einstein (São Paulo)

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Objective:To analyze the immunoexpression of the COX-2, p53, and caspase-3 proteins in colorectal adenomas and non-neoplastic mucosa.Methods:72 individuals were subjected to colonoscopy, which provided 50 samples of adenomas and 45 samples of non-neoplastic colorectal mucosa. The tissue samples were obtained via the tissue microarray technique and subjected to immunohistochemical analysis using primary anti-p53, anti-COX-2, and anti-caspase-3 antibodies. The positivity and intensity of the immunoreaction were classified. The analyzed variables were as follows: site of the adenomas in the colon, degree of dysplasia, size, and score of positivity and intensity of immunoexpression of the p-53, caspase-3, and COX-2 proteins.Results:The immunoexpression of mutated protein p53 was positive in 30 (60%) adenoma samples and negative in 20 (40%) adenoma samples. The immunoexpression of mutated protein p53 was negative in 39 (86.6%) samples and positive in 6 (13.3%) samples of the non-neoplastic colorectal mucosa (p<0.0001). Significant differences were seen between both the largest size (p=0.006) and the highest degree of dysplasia (p<0.0001) of the adenomas and the intensity of immunoexpression of mutated protein p53. The positivity and intensity of immunoexpression of COX-2 (p=0.14) and caspase-3 (p=0.23) showed no significant differences between the adenomas and the non-neoplastic colorectal mucosa.Conclusion:Mutated protein p53 was hyperexpressed in the adenomas compared with the non-neoplastic mucosa. Greater size and greater degree of dysplasia in the adenomas were associated with higher expression of mutated protein p53. The immunoexpression of COX-2 and caspase-3 in the adenomas did not exhibit a correlation with the anatomical-pathological features of the tumors and did not differ from the corresponding expression levels in the non-neoplastic mucosa.

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Relation of the Expression of Cyclooxygenase-2 in Colorectal Adenomas and Adenocarcinomas to Angiogenesis and Prognosis

Cited by 11 publications

References 26 publications

The Importance of Fecal and Plasma CEA, COX-2, MMP-7, and TIMP-1 in the Diagnosis of Colorectal Cancer

The Importance of Fecal and Plasma CEA, COX-2, MMP-7, and TIMP-1 in the Diagnosis of Colorectal Cancer

Ocoxin® oral solution slows down tumor growth in an experimental model of colorectal cancer metastasis to the liver in Balb/c mice

Imunoexpressão das proteínas COX-2, p53 e caspase-3 em adenoma colorretal e mucosa não neoplásica

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