• Journal of Digestive Cancer Research
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• v.4 no.2
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• pp.64-76
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• 2016

The step-wise process of colorectal carcinogenesis from aberrant crypt foci, adenoma to adenocarcinoma, is relatively suitable for chemopreventive intervention. Accumulated evidences have revealed that maintaining an undifferentiated state (stemness), inflammation, and oxidative stress play important roles in this colon carcinogenesis process. However, appropriate molecular targets that are applicable to chemopreventive intervention regarding those three factors are still unclear. In this review, we summarized appropriate molecular targets by identification and validation of the prospective targets from a comprehensive overview of data that showed colon cancer preventive effects in clinical trials, epidemiological studies and basic research. We first selected a study that used aspirin, statins and metformin from FDA approved drugs, and epigallocatechin-gallate and curcumin from natural compounds as potential chemopreventive agents against colon cancer because these agents are considered to be promising chemopreventive agents. Experimental and observational data revealed that there are common target molecules in these potential chemopreventive agents: T-cell factor/lymphoid enhancer factor (TCF/LEF), nuclear factor-&B (NF-κB) and nuclear factor-erythroid 2-related factor 2(NRF2). Moreover, these targets, TCF/LEF, NF-κB and NRF2, have been also indicated to suppress maintenance of the undifferentiated state, inflammation and oxidative stress, respectively. In the near future, novel promising candidate agents for colon cancer chemoprevention could be identified by integral evaluation of their effects on these three transcriptional activities.

• International Journal of Oral Biology
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• v.46 no.1
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• pp.7-14
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• 2021

Vinpocetine induces anti-inflammatory effects in various inflammatory diseases via the inhibition of phosphodiesterase type-1-independent nuclear factor-κB signaling pathway and the release of inflammatory cytokines. In this study, we investigated the effect of vinpocetine on the proliferation of colon cancer cells and its underlying molecular mechanisms. Our data showed that vinpocetine inhibits the viability and proliferation of colon cancer cells. Vinpocetine treatment induced cell death in HCT116 cells, which the percentages of sub-G1 phase were significantly increased, and the apoptosis-related genes were regulated after HCT116 cells were treated with vinpocetine. In sum, our findings indicated that vinpocetine could be a therapeutically useful candidate in the treatment of colon cancer.

• Journal of Yeungnam Medical Science
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• v.26 no.2
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• pp.114-119
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• 2009

Colon cancer is the second most common malignancy in Korea. It is classified as superficial type, the mass type, the ulcerative type, the ulceroinfiltrative type, the diffuse infiltrative type and the unclassified type according to the colonoscopic findings. We report here on a case of colon cancer that was initially misdiagnosed as acute infectious colitis at the initial presentation. A 64-year-old man visited to Yeungnam University Hospital for watery diarrhea and lower abdominal pain. Colonoscopy revealed long segmental edematous mucosa and hyperemic mucosa with stenosis in the transverse colon. He was diagnosed as having acute infectious colitis according to the colonoscopic finding. However, two days later after colonoscopy, he visited the emergency room for hematochezia. We performed computerized tomography (CT) and obtained blood samples to find the origin of the bleeding. We found thickening of the transverse colon lumen and ascites on the CT finding and an elevated level of tumor markers; we also obtained the results of the colonoscopic biopsy that was done via colonoscopy. He was finally diagnosed as having colon cancer with carcinomatosis, a poorly differentiated adenocarcinoma.

• Journal of Microbiology and Biotechnology
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• v.14 no.4
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• pp.852-858
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• 2004

The morbidity and mortality of colon cancer are increasing, because of the westernization of food habit. Probiotics such as lactic acid bacteria (LAB) have been known to play an important role in retarding colon carcinogenesis by possibly influencing metabolic, immunologic, and protective functions in the colon. In this study, we evaluated the effect of B. polyfermenticus SCD on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) induced DNA damage in CHO-K, cells and human lymphocytes, and on proliferation of human colon cancer cell. Using the Comet assay to detect DNA damage, we found that B. polyfermenticus SCD protected cells from the DNA damage induced by MNNG in $CHO-K_1$ cells and in human lymphocytes. B. polyfermenticus SCD was also found to inhibit the growth of colon cancer cells in a dose-dependent manner, detected by the MTT assay. These results indicate that B. polyfermenticus SCD has the potential to inhibit not only DNA damage induced by a carcinogen, but also the proliferation of colon cancer cells.

• Annals of Surgical Treatment and Research
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• v.96 no.2
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• pp.78-85
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• 2019

Purpose: Insistence that total regression of primary tumor would not represent long-term oncologic outcomes has been raised. Therefore, this study aimed to evaluate the outcomes of these patients after preoperative chemoradiotherapy (PCRT) and radical surgery and to evaluate the associated risk factors. Methods: We included 189 patients with rectal cancer who showed total regression of the primary tumor after PCRT, followed by radical resection, between 2001 and 2012. Recurrence-free survival (RFS) was calculated using the Kaplan-Meier method, and the results were compared with 77 patients with Tis rectal cancer who received only radical resection. Factors associated with RFS were evaluated using Cox regression analysis. Results: Sphincter-saving resection was performed for 146 patients (77.2%). Adjuvant chemotherapy was administered to 168 patients (88.9%). During the follow-up period, recurrence occurred in 17 patients (9%). The 5-year RFS was 91.3%, which was significantly lower than that of patients with Tis rectal cancer without PCRT (P = 0.005). In univariate analysis, preoperative CEA and histologic differentiation were associated with RFS. However, no factors were found to be associated with RFS. Conclusion: RFS was lower in patients with total regression of primary rectal cancer after PCRT than in those with Tis rectal cancer without PCRT, and it would not be considered as the same entity with early rectal cancer or "disappeared tumor" status.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.11
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• pp.4991-4998
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• 2016

Objective: This research was conducted to explore mechanisms behind the potency of quercetin in inhibiting colon cancer induced in an experimental model. Materials and Methods: Forty adult male rats of Wistar strain were distributed into 4 groups; a negative control group, a colon cancer bearing group, a quercetin-treated group and a 5-fluorouracil (5-FU)-treated group. Serum TAG72 and GAL3 levels were quantified by ELISA. Colonic Wnt5a and Axin-1 gene expression was estimated by PCR. In addition, colonic tissues were subjected to immunohistochemical examination of Bax expression and histological investigation of histopathological alterations. Results: Quercetin elicited significant reduction in serum TAG72 and GAL3 levels, in addition to significant suppression of colonic Wnt5a gene expression and amplification of colonic Axin-1 gene expression. Also, it caused moderate positive reaction for Bax in mucosal epithelium. Conclusion: The present research provides experimental evidence about the activity of quercetin in the colon cancer of rats. Inhibitory effects on cancer development might be ascribable to regulatory action on Wnt signaling and induction of apoptosis.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7245-7249
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• 2014

Glucose regulated protein 78 (GRP78) is usually recognized as a chaperone in the endoplasmic reticulum. However, increasing evidence indicates that GRP78 can be translocated to the cell surface, acting as a signaling receptor for a variety of ligands. Since little is known about the secretion of GRP78 and its role in the progression of colon cancer we here focused on GRP78 from colon cancer cells, and purified GRP78 protein mimicking the secreted GRP78 was able to utilize cell surface GRP78 as its receptor, activating downstream PI3K/Akt and Wnt/${\beta}$-catenin signaling and promote colon cancer cell proliferation. Our study revealed a new mode of action of autocrine GRP78 in cancer progression: secreted GRP78 binds to cell surface GRP78 as its receptor and activates intracellular proliferation signaling.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.1083-1087
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• 2013

Background: Colorectal cancer has several modifiable behavioural risk factors but their relationship to the risk of colon and rectum cancer separately and between countries with high and low incidence is not clear. Methods: Data from participants in the Asia Pacific Cohort Studies Collaboration (APCSC) were used to estimate mortality from colon (International Classification of Diseases, revision 9 (ICD-9) 153, ICD-10 C18) and rectum (ICD-9 154, ICD-10 C19-20) cancers. Data on age, body mass index (BMI), serum cholesterol, height, smoking, physical activity, alcohol and diabetes mellitus were entered into Cox proportional hazards models. Results: 600,427 adults contributed 4,281,239 person-years follow-up. The mean ages (SD) for Asian and Australia/New Zealand cohorts were 44.0 (9.5) and 53.4 (14.5) years, respectively. 455 colon and 158 rectum cancer deaths were observed. Increasing age, BMI and attained adult height were associated with increased hazards of death from colorectal cancer, and physical activity was associated with a reduced hazard. After multiple adjustment, any physical activity was associated with a 28% lower hazard of colon cancer mortality (HR 0.72, 95%CI 0.53-0.96) and lower rectum cancer mortality (HR 0.75, 95%CI 0.45-1.27). A 2cm increase in height increased colon and all colorectal cancer mortality by 7% and 6% respectively. Conclusions: Physical inactivity and greater BMI are modifiable risk factors for colon cancer in both Western and Asian populations. Further efforts are needed to promote physical activity and reduce obesity while biological research is needed to understand the mechanisms by which they act to cause cancer mortality.

• Journal of Preventive Medicine and Public Health
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• v.55 no.5
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• pp.475-484
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• 2022

Objectives: This study aimed to determine the association between metabolic syndrome (MetS) and the incidence of colorectal cancer (CRC) in Korean women with obesity. Methods: Cancer-free women (n=6 142 486) aged 40-79 years, who underwent National Health Insurance Service health examinations in 2009 and 2010 were included. The incidence of CRC was followed until 2018. The hazard ratio (HR) of MetS for the incidence of colon and rectal cancer was analyzed according to body mass index (BMI) categories, adjusting for confounders such as women's reproductive factors. In addition, the heterogeneity of associations across BMI categories was assessed. Results: Women with MetS were at increased risk of colon and rectal cancer compared to women without MetS (HR, 1.20; 95% confidence interval [CI], 1.16 to 1.23 and HR,1.15; 95% CI, 1.11 to 1.20), respectively. The HR of MetS for colon cancer across BMI categories was 1.12 (95% CI, 1.06 to 1.19), 1.14 (95% CI, 1.08 to 1.20), and 1.16 (95% CI, 1.12 to 1.21) in women with BMIs <23.0 kg/m², 23.0-24.9 kg/m², and ≥25.0 kg/m², respectively. The HR of MetS for rectal cancer across corresponding BMI categories was 1.16 (95% CI, 1.06 to 1.26), 1.14 (95% CI, 1.05 to 1.23), and 1.13 (95% CI, 1.06 to 1.20). The heterogeneity of associations across BMI categories was not significant in either colon or rectal cancer (p=0.587 for colon cancer and p=0.927 for rectal cancer). Conclusions: Women with MetS were at increased risk of colon and rectal cancer. Clinical and public health strategies should be considered for primary CRC prevention with an emphasis on improving women's metabolic health across all BMI groups.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1023-1035
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• 2016

The purpose of this study was to investigate the role of colon cancer stem cells (CSCs) during chemically-induced rat multi-step colon carcinogenesis with or without the treatment with a specific cyclooxygenase-2 inhibitor drug (celecoxib). Two experiments were performed, the first, a short term 12 week colon carcinogenesis bioassay in which only surrogate markers for colon cancer, aberrant crypt foci (ACF) lesions, were formed. The other experiment was a medium term colon cancer rat assay in which tumors had developed after 32 weeks. Treatment with celecoxib lowered the numbers of ACF, as well as the tumor volumes and multiplicities after 32 weeks. Immunohistochemical proliferating cell nuclear antigen (PCNA) labeling indexes LI (%) were downregulated after treatment by celecoxib. Also different cell surface antigens known to associate with CSCs such as the epithelial cell adhesion molecule (EpCAM), CD44 and CD133 were compared between the two experiments and showed differential expression patterns depending on the stage of carcinogenesis and treatment with celecoxib. Flow cytometric analysis demonstrated that the numbers of CD133 cells were increased in the colonic epithelium after 12 weeks while those of CD44 but not CD133 cells were increased after 32 weeks. Moreover, aldehyde dehydrogenase-1 activity levels in the colonic epithelium (a known CSC marker) detected by ELISA assay were found down-regulated after 12 weeks, but were up-regulated after 32 weeks. The data have also shown that the protective effect of celecoxib on these specific markers and populations of CSCs and on other molecular processes such as apoptosis targeted by this drug may vary depending on the genetic and phenotypic stages of carcinogenesis. Therefore, uncovering these distinction roles of CSCs during different phases of carcinogenesis and during specific treatment could be useful for targeted therapy.