• Journal of Medicine and Life Science
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• v.15 no.2
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• pp.42-45
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• 2018

Colorectal cancer (CRC) is a third leading cause of cancer-related death in cancer patients. Sporadic and inflammation-related colon carcinogenesis are major mechanism of colorectal cancer. In vivo CRC models have been developed and implicated to understand their mechanisms upon a different type of CRC. Moreover, recently animal models have played important roles in chemopreventive and preclinical trials over the years. In this mini-review, the aim is to introduce various animal models of CRC and help the understanding to establish in vivo experimental plans according to the cancer type of CRC.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.5
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• pp.1945-1952
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• 2015

Inflammatory bowel disease (IBD) is a disease strongly associated with colorectal cancer (CRC) as a well-known precancerous condition. Alterations in DNA methylation and mutation in K-ras are believed to play an early etiopathogenic role in CRC and may also an initiating event through deregulation of molecular signaling. Epigenetic silencing of APC and SFRP2 in the WNT signaling pathway may also be involved in IBD-CRC. The role of aberrant DNA methylation in precancerous state of colorectal cancer (CRC) is under intensive investigation worldwide. The aim of this study was to investigate the status of promoter methylation of MGMT-B, APC1A and SFRP2 genes, in inflamed and normal colon tissues of patients with IBD compared with control normal tissues. A total of 52 IBD tissues as well as corresponding normal tissues and 30 samples from healthy participants were obtained. We determined promoter methylation status of MGMT-B, SFRP2 and APC1A genes by chemical treatment with sodium bisulfite and subsequent MSP. The most frequently methylated locus was MGMT-B (71%; 34 of 48), followed by SFRP2 (66.6 %; 32 of 48), and APC1A (43.7%; 21 of 48). Our study demonstrated for the first time that hypermethylation of the MGMT-B and the SFRP2 gene promoter regions might be involved in IBD development. Methylation of MGMT-B and SFRP2 in IBD patients may provide a method for early detection of IBD-associated neoplasia.

• Clinical Endoscopy
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• v.56 no.2
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• pp.245-251
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• 2023

A plethora of paraneoplastic syndromes have been reported as remote effects of colorectal carcinoma (CRC). However, there is a dearth of data pertaining to the association of this cancer with demyelinating neuropathies. Herein, we describe the case of a young woman diagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP). Treatment with intravenous immunoglobulins and prednisone did not improve her condition, and her neurological symptoms worsened. Subsequently, she was readmitted with exertional dyspnea, lightheadedness, malaise, and black stools. Colonoscopy revealed a necrotic mass in the ascending colon, which directly invaded the second part of the duodenum. Pathologic results confirmed the diagnosis of locally advanced CRC. Upon surgical resection of the cancer, her CIDP showed dramatic resolution without any additional therapy. Patients with CRC may develop CIDP as a type of paraneoplastic syndrome. Clinicians should remain cognizant of this potential association, as it is of paramount importance for the necessary holistic clinical management.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.6
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• pp.2647-2650
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• 2014

Background: Colorectal cancers(CRC) are the third most common cancer in the western world, with surgery preferred for management of non-metastatic disease and post surgical treatment usually arranged according to the TNM staging system. However, there is still prognostic variation between patients who have the same stage. It is increasingly recognized that variations within disease course and clinical outcome in colorectal cancer patients are influenced by not only oncological characteristics of the tumor itself but also host response factors. Recent studies have shown correlation between the inflammatory response and clinical outcomes in various cancers. The neutrophil/lymphocyte ratio (NLR) has been described as a marker for immune response to various stimuli including cancer. Material-Methods: Two hundred eighty-one CRC patients were included in our retrospective analysis, separated into two groups according to a cut-off value for the NLR. Patient data including age, gender, vertical penetration, anatomic location, and differentiation of the tumor, TNM stage, survival rate, and disease-free survival were analyzed for correlations with the NLR. Results: Using ROC curve analysis, we determined a cut-off value of 2.2 for NLR to be best to discriminate between patient survival in the whole group. In univariate analysis, high pretreatment NLR (p=0.001, 95%CI 1.483-4.846), pathologic nodal stage (p<0.001, 95%CI 1.082-3.289) and advanced pathologic TNM stage (p<0.001, 95%CI 1.462-4.213) were predictive of shorter survival. In multivariate analysis, advanced pathologic TNM stage (p=0.001, 95%CI 1.303-26.542) and high pretreatment NLR (p=0.005, 95%CI 1.713-6.378) remained independently associated with poor survival. Conclusions: High pre-treatment NLR is a significant independent predictor of shorter survival in patients with colorectal cancer. This parameter is a simple, easily accessible laboratory value for identifying patients with poorer prognosis.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.12
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• pp.5047-5056
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• 2016

Colorectal cancer (CRC) is a major worldwide health problem owing to its high prevalence and mortality rates. Carcinogenesis in the colon is a multistage and multifactorial process. An imbalance between free radical exposure and anti-oxidant defense systems may leads to oxidative stress and attack of macromolecules which can alter signal transduction pathways and gene expression. Consequently, oxidative damage can lead to cellular dysfunction and contribute to pathophysiological processes in a variety of diseases including CRC. One factor tightly associated with CRC is chronic inflammation, which can be present from the earliest stage of tumor onset. Unpolished rice is an attractive chemoprevention in CRC due to their anti-oxidant and anti-inflammatory activities. The aim of this paper is to review evidence linking oxidative stress and inflammation to CRC and to provide essential background information for understanding future research on oxidative stress and inflammation on CRC. Mechanisms of action of unpolished rice in CRC carcinogenesis are also discussed.

• Annals of Coloproctology
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• v.34 no.6
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• pp.299-305
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• 2018

Purpose: Inflammatory bowel disease (IBD) in Korea has been increasing in recent years, but accurate statistics about operations for IBD are lacking. The purpose of this study was to investigate the trends and current status of IBD surgeries in Korea. Methods: Using a national database from the Korea Health Insurance Review and Assessment Service, we analyzed data from patients who underwent surgery for Crohn disease and ulcerative colitis from January 2009 to October 2016. Results: The mean number of patients who underwent surgery for Crohn disease was 791.8 per year. Colorectal surgery, small bowel surgery, and anal surgery were performed fairly often (31.2%, 29.4%, 39.4%, respectively), and laparoscopic surgery continued to increase, recently exceeding 30%. About 50% of Crohn patients used biologics before and after surgery, and those patients also underwent a relatively high rate of anal surgeries (44.2%). The mean number of patients who underwent surgery for ulcerative colitis was 247.6 per year. Colorectal surgery accounted for more than half of all operations, and laparoscopic surgery has been increasing rapidly, having been performed in about 60% of patients in recent years. The incidence of colorectal cancer in patients with ulcerative colitis was very high and increased rapidly during the study period, reaching about 80%. Conclusion: The number of patients undergoing laparoscopic surgery for IBD in Korea has increased significantly. Biologics are actively used by patients with Crohn disease, with a high proportion of anal surgeries required. Many of the surgical indications for ulcerative colitis have shifted into colorectal cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.14
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• pp.5501-5508
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• 2014

Luteolin, 3', 4', 5,7-tetrahydroxyflavone, belongs to a group of naturally occurring compounds called flavonoids that are found widely in the plant kingdom. It possesses many beneficial properties including antioxidant, anti-inflammatory, anti-bacterial, anti-diabetic and anti-proliferative actions. Colorectal cancer (CRC) is a leading cause of cancer related deaths worldwide. Many signaling pathways are deregulated during the progression of colon cancer. In this review we aimed to analyze the protection offered by luteolin on colon cancer. During colon cancer genesis, luteolin known to reduce oxidative stress thereby protects the cell to undergo damage in vivo. Wnt/${\beta}$-catenin signaling, deregulated during neoplastic development, is modified by luteolin. Hence, luteolin can be considered as a potential drug to treat CRC.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7673-7677
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• 2014

Background: Patients with long-standing inflammatory bowel disease (IBD) have an increased risk of developing colorectal cancer (CRC). Colon cancer risk in IBD increases with longer duration and greater anatomic extent of colitis, the presence of primary sclerosing cholangitis, family history of CRC and degree of inflammation of the bowel. This study aimed to characterize the histopathological pattern of benign colorectal diseases among Saudi patients and to highlight age and gender variations of lesions as base line data for future studies to investigate the link between benign/IBD and colorectal cancers in the local population. Materials and Methods: The materials consisted of 684 biopsies, reported as benign (excluding malignancies and polyps) at the Department of Pathology, King Fahad Hospital, Madinah, Saudi Arabia from January 2006 to December 2013. Data collected and entered in MS-Excel and were analyzed using SPSS-20. Results: Of 684 colorectal tissues reviewed, 408 specimens (59.6%) were from male patients and 276 specimens (40.4%) were from females giving a male: female ratio of 1.5:1. Age of the patients ranged from 4 to 75 years with a mean of 39.6 years. The most frequent histologic diagnosis was a chronic non specific proctocolitis followed by ulcerative colitis, accounting respectively for 52.6% and 31.7% of all cases. These were followed by Crohn's disease 22 (3.2%), ischemic bowel disease 20 (2.9%), diverticular disease 14 (2%), eosinophilic colitis 12 (1.7%) and solitary rectal ulcer 12 (1.7%). A minority of 21 patients (3.1%) were cases of acute nonspecific proctocolitis, schistosomiasis, tuberculosis, volvulus and pseudomembranous colitis. Conclusions: These data show that although chronic non specific proctocolitis and ulcerative colitis were the dominant diagnoses, Crohn's disease, ischemic bowel disease and diverticular disease also existed to a lesser extent and should be considered in the differential diagnosis of benign colorectal diseases. This study provides a base line data for future studies which would be taken up to investigate the link between benign/IBD and colorectal cancers in the local population.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.2689-2698
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• 2013

Epithelial-to-mesenchymal transition (EMT) is a collection of events that allows the conversion of adherent epithelial cells, tightly bound to each other within an organized tissue, into independent fibroblastic cells possessing migratory properties and the ability to invade the extracellular matrix. EMT contributes to the complex architecture of the embryo by permitting the progression of embryogenesis from a simple single-cell layer epithelium to a complex three-dimensional organism composed of both epithelial and mesenchymal cells. However, in most tissues EMT is a developmentally restricted process and fully differentiated epithelia typically maintain their epithelial phenotype. Recently, elements of EMT, specially the loss of epithelial markers and the gain of mesenchymal markers, have been observed in pathological states, including epithelial cancers. Increasing evidence has confirmed its presence in human colon during colorectal carcinogenesis. In general, chronic inflammation is considered to be one of the causes of many human cancers including colorectal cancer(CRC). Accordingly, epidemiologic and clinical studies indicate that patients affected by ulcerative colitis and Crohn's disease, the two major forms of inflammatory bowel disease, have an increased risk of developing CRC. A large body of evidence supports roles for the SMAD/STAT3 signaling pathway, the NF-kB pathway, the Ras-mitogenactivated protein kinase/Snail/Slug and microRNAs in the development of colorectal cancers via epithelial-tomesenchymal transition. Thus, EMT appears to be closely involved in the pathogenesis of colorectal cancer, and analysis refered to it can yield novel targets for therapy.

• Nutrition Research and Practice
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• v.11 no.2
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• pp.90-96
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• 2017

BACKGROUND/OBJECTIVES: Although the antioxidative effects of lycopene are generally known, the molecular mechanisms underlying the anti-inflammatory properties of lycopene are not fully elucidated. This study aimed to examine the role and mechanism of lycopene as an inhibitor of inflammation. METHODS/MATERIALS: Lipopolysaccharide (LPS)-stimulated SW 480 human colorectal cancer cells were treated with 0, 10, 20, and $30{\mu}M$ lycopene. The MTT assay was performed to determine the effects of lycopene on cell proliferation. Western blotting was performed to observe the expression of inflammation-related proteins, including nuclear factor-kappa B ($NF-{\kappa}B$), inhibitor kappa B ($I{\kappa}B$), mitogen-activated protein kinase (MAPK), extracellular signal-related kinase (ERK), c-jun NH2-terminal kinase (JNK), and p38 (p38 MAP kinase). Real-time polymerase chain reaction was performed to investigate the mRNA expression of tumor necrosis factor ${\alpha}$ ($TNF-{\alpha}$), interleukin-1 beta ($IL-1{\beta}$), interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). Concentrations of nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) were determined via enzyme-linked immunosorbent assays. RESULTS: In cells treated with lycopene and LPS, the mRNA expression of $TNF-{\alpha}$, $IL-1{\beta}$, IL-6, iNOS, and COX-2 were decreased significantly in a dose-dependent manner (P < 0.05). The concentrations of $PGE_2$ and NO decreased according to the lycopene concentration (P < 0.05). The protein expressions of $NF-{\kappa}B$ and JNK were decreased significantly according to lycopene concertation (P < 0.05). CONCLUSIONS: Lycopene restrains $NF-{\kappa}B$ and JNK activation, which causes inflammation, and suppresses the expression of $TNF-{\alpha}$, $IL-1{\beta}$, IL-6, COX-2, and iNOS in SW480 human colorectal cancer cells.