• 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.

• Korean Journal of Radiology
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• v.24 no.9
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• pp.849-859
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• 2023

Objective: The prognostic value of the volume and density of skeletal muscles in the abdominal waist of patients with colon cancer remains unclear. This study aimed to investigate the association between the automated computed tomography (CT)-based volume and density of the muscle in the abdominal waist and survival outcomes in patients with colon cancer. Materials and Methods: We retrospectively evaluated 474 patients with colon cancer who underwent surgery with curative intent between January 2010 and October 2017. Volumetric skeletal muscle index and muscular density were measured at the abdominal waist using artificial intelligence (AI)-based volumetric segmentation of body composition on preoperative pre-contrast CT images. Patients were grouped based on their skeletal muscle index (sarcopenia vs. not) and muscular density (myosteatosis vs. not) values and combinations (normal, sarcopenia alone, myosteatosis alone, and combined sarcopenia and myosteatosis). Postsurgical disease-free survival (DFS) and overall survival (OS) were analyzed using univariable and multivariable analyses, including multivariable Cox proportional hazard regression. Results: Univariable analysis showed that DFS and OS were significantly worse for the sarcopenia group than for the non-sarcopenia group (P = 0.044 and P = 0.003, respectively, by log-rank test) and for the myosteatosis group than for the non-myosteatosis group (P < 0.001 by log-rank test for all). In the multivariable analysis, the myosteatotic muscle type was associated with worse DFS (adjusted hazard ratio [aHR], 1.89 [95% confidence interval, 1.25-2.86]; P = 0.003) and OS (aHR, 1.90 [95% confidence interval, 1.84-3.04]; P = 0.008) than the normal muscle type. The combined muscle type showed worse OS than the normal muscle type (aHR, 1.95 [95% confidence interval, 1.08-3.54]; P = 0.027). Conclusion: Preoperative volumetric sarcopenia and myosteatosis, automatically assessed from pre-contrast CT scans using AI-based software, adversely affect survival outcomes in patients with colon cancer.

• Communications for Statistical Applications and Methods
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• v.13 no.1
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• pp.177-190
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• 2006

The aim of this study is to propose a Bayesian model for fitting mortality rate of colon cancer. For the analysis of mortality rate of a disease, factors such as age classes of population and spatial characteristics of the location are very important. The model proposed in this study allows the age class to be a random effect in addition to its conventional role as the covariate of a linear regression, while the spatial factor being a random effect. The model is fitted using Metropolis-Hastings algorithm. Posterior expected predictive deviances, standardized residuals, and residual plots are used for comparison of models. It is found that the proposed model has smaller residuals and better predictive accuracy. Lastly, we described patterns in disease maps for colon cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3747-3752
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• 2015

Background: Colorectal cancer is one of the most commonly occurring cancers in China. Dietary fibre has been thought to decrease the risk of colorectal cancer in Western countries. However, studies investigating the association between dietary fibre (particularly soluble and insoluble fibres) and colorectal cancer have hitherto been lacking in China. Objective: This case-control study examined the effect of dietary fibre intake on the risk of colorectal cancer, stratified by tumour site. Materials and Methods: The study included 265 cases (colon cancer, 105; rectal cancer, 144; colon and rectal cancer, 16) and 252 controls residing in Qingdao. A food frequency questionnaire that included 121 food items was used to collect dietary information. Odds ratio (OR) and 95% confidence intervals (CI) were calculated using unconditional logistic regression analysis. Results: For food groups, controls in the study consumed more vegetables, soy food and total fibre than did colorectal cancer patients (p<0.05). The intakes of fruit, meat and sea-food did not differ significantly between cases and controls. However, we did not find any association between soy food intake and colon cancer. We observed inverse associations between total fibre intake and colorectal, colon and rectal cancer (Q4 vs Q1: OR=0.44, 95%CI, 0.27-0.73; OR=0.40, 95%CI, 0.21-0.76; OR=0.52, 95%CI, 0.29-0.91). Vegetable fibre intake showed similar inverse associations (Q4 vs Q1: OR=0.51, 95%CI, 0.31-0.85; OR=0.48, 95%CI, 0.25-0.91; OR=0.53, 95%CI, 0.29-0.97). In addition, inverse associations were observed between soluble fibre and insoluble fibre and both colorectal cancer and colon cancer. No relationship was found between colorectal cancer and fruit, soy or grain fibre intakewhen the results were stratified by tumour site. Conclusions: The present study suggests that vegetable fibre and total fibre play very important roles in protecting against colorectal cancer. Soluble and insoluble fibres were inversely associated with only colorectal cancer and colon cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4263-4266
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• 2012

Colorectal cancer has become a major disease threatening human health. To establish animal models that exhibit the characteristics of human colorectal cancer will not only help to study the mechanisms underlying the genesis and development effectively, but also provide ideal carriers for the screening of medicines and examining their therapeutic effects. In this study, we established a stable, colon cancer nude mouse model highly expressing green fluorescent protein (GFP) for spontaneous metastasis after surgical orthotopic implantation (SOI). GFP-labeled colon cancer models for metastasis after SOI were successfully established in all of 15 nude mice and there were no surgery-related complications or deaths. In week 3, primary tumors expressing GFP were observed in all model animals under fluoroscopy and two metastatic tumors were monitored by fluorescent imaging at the same time. The tumor volumes progressively increased with time. Seven out of 15 tumor transplanted mice died and the major causes of death were intestinal obstruction and cachexia resulting from malignant tumor growth. Eight model animals survived at the end of the experiment, 6 of which had metastases (6 cases to mesenteric lymph nodes, 4 hepatic, 2 pancreatic and 1 mediastinal lymph node). Our results indicate that our GFP-labeled colon cancer orthotopic transplantation model is useful with a high success rate; the transplanted tumors exhibit similar biological properties to human colorectal cancer, and can be used for real-time, in vivo, non-invasive and dynamic observation and analysis of the growth and metastasis of tumor cells.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.6
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• pp.2237-2243
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• 2015

Background: Adjuvant chemotherapy improves survival in Dukes C colon cancers post-curative resection. However, the evidence for a role with Dukes B lesions remains unproven despite frequent use for disease characterized by poor prognostic features. In view of limited Asia-specific data, this study aimed to determine survival outcomes and identify prognostic factors in a tertiary teaching hospital in Malaysia. Materials and Methods: A total of 116 subjects who underwent curative surgery with and without adjuvant chemotherapy for Duke B and C primary colon adenocarcinomas diagnosed from 2004-2009 were recruited and data were collected retrospectively. Five-year overall survival (OS) and disease free survival (DFS) were analysed using Kaplan-Meier survival analysis and log-rank (Mantel-Cox) test. Prognostic factors were determined using Cox proportional hazards regression with both univariate and multivariate analyses. Results: The survival analysis demonstrated a 5-year OS of 74.0% for all patients, with 74.9% for Dukes C subjects receiving chemotherapy compared to 28.6% in those not receiving chemotherapy (p=0.001). For Dukes B disease, the 5-year survival rate was 82.6% compared to 75.0% for subjects receiving and not receiving chemotherapy, respectively (p=0.17). Independent prognostic factors identified included a CEA level more than 3.5 ng/ml (hazard ratio (HR)=4.78; p=0.008), serosal involvement (HR=3.75; p=0.028) and completion of chemotherapy (HR= 0.20; p=0.007). Conclusions: In a regional context, this study supports current evidence from the West that adjuvant chemotherapy improves survival in Dukes C colon cancers post curative surgery. However, although a clear benefit has yet to be proven for Dukes B disease, our results suggest survival improvement in selected cases.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1605-1610
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• 2012

Gelam and Nenas monofloral honeys were investigated in this study for their chemopreventive effects against HT 29 colon cancer cells. MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolim) assays showed more effective inhibition of colon cancer cells proliferation by Gelam honey with $IC_{50}$ values of 39.0 mg/ml and 85.5 mg/ml respectively after 24 hours of treatment. Alkali comet assays revealed both honeys increased DNA damage significantly in a dose dependent manner. In addition, annexin V-FITC/PI flow cytometry demonstrated that at $IC_{50}$ concentrations and above, both Gelam and Nenas honeys induced apoptosis significantlyat values higher than for necrosis (p<0.05). Measurement of prostaglandin $E_2$ ($PGE_2$) confirmed that Gelam and Nenas honeys reduced its production in $H_2O_2$ inflammation-induced colon cancer cells. In conclusion, our study indicated and confirmed that both Gelam and Nenas honeys are capable of suppressing the growth of HT 29 colon cancer cells by inducing apoptosis and suppressing inflammation.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.1
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• pp.73-80
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• 2016

Colorectal cancer is a very prevalent diagnosed cancer. The current study was performed in order to examine the role of BRAE (Basella rubra aqueous extract) in regulating aberrant crypt foci (ACF) formation, cell proliferation and inhibition of apoptosis in a colon carcinogenesis model in male Wistar rats. Rats were randomly allocated into six groups. Group I served as control, and group II acted as a drug control administered BRAE (250mg/kg b.w.) orally for 30 weeks. Rats in group III-VI were given subcutaneous injections of DMH (25mg/kg b.w. weekly) for 15 weeks to initiate colon carcinogenesis. Those in group IV and VI were administered BRAE along with DMH injections. Rats in group V were administered with BRAE after cessation of DMH injection. After 30 weeks of experimental period colons were obtained from experimental groups and analyzed for ACF incidence, argyrophilic nucleolar organizing region-associated proteins (AgNOR) count, histopathological and immunohistochemical changes. Only in DMH exposed groups were ACF and AgNOR numbers increased. Administration of BRAE appreciably decreased the numbers of ACF and AgNOR in BRAE treated groups. Histopathological findings revealed a high level of dysplastic changes with decreased number of goblet cells found only in only DMH injected rats. Administration of BRAE in treated group rats reversed these changes. Expression markers for cell proliferation (PCNA and Ki67) were elevated in DMH treated rats, but reduced with BRAE treatement. This expression was reversed with apoptosis markers (p53 and Caspase-3). Thus the results results of the present study were found to be significant and confirmed the potential efficacy of BRAE against colon carcinogenesis.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5331-5339
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• 2013

Colorectal cancer is one of the leading causes of cancer death, both in men and women. This study investigated the effects of Amorphophallus campanulatus tuber methanolic extract (ACME) on aberrant crypt foci (ACF) formation, colonic cell proliferation, lipid peroxidative damage and the antioxidant status in a long term preclinical model of 1, 2-dimethylhydrazine (DMH) induced colon carcinogenesis in rats. Male Wistar rats were divided into six groups, viz., group I rats served as controls; group II rats treated as drug controls receiving 250 mg/kg body weight of ACME orally; group III rats received DMH (20 mg/kg body weight) subcutaneously once a week for the first 15 weeks; groups IV, V and VI rats received ACME along with DMH during the initiation, post-initiation stages and the entire period of the study, respectively. All the rats were sacrificed at the end of 30 weeks and the intestinal and colonic tissues from different groups were subjected to biochemical and histological studies. Administration of DMH resulted in significant ($p{\leq}0.05$) intestinal and colonic lipid peroxidation (MDA) and reduction of antioxidants such as catalase, glutathione peroxidase, glutathione reductase, glutathione-Stransferase and reduced glutathione. Whereas the supplementation of ACME significantly ($p{\leq}0.05$) improved the intestinal and colonic MDA and reduced glutathione levels and the activities of antioxidant enzymes in DMH intoxicated rats. ACME administration also significantly suppressed the formation and multiplicity of ACF. In addition, the DMH administered rats showed amplified expression of PCNA in the colon and decreased expression of this proliferative marker was clearly noted with initiation, post-initiation and entire period of ACME treatment regimens. These results indicate that ACME could exert a significant chemopreventive effect on colon carcinogenesis induced by DMH.

• Herbal Formula Science
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• v.16 no.2
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• pp.171-182
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• 2008

The aqueous extract of Schisandra chinensis, Evodia rutaecarpa and meal (SEM-Ex) has been traditionally used in the Oriental countries as an astringent. However, little is known about the effects of aqueous extract of SEM-Ex on dextran-sulfate sodium (DSS)-induced colitis in mice. In this study, we investigated the protective effects of SEM-Ex on DSS-induced colitis in mice. An experimental colitis was induced by daily treatment with 5% DSS. SEM-Ex was orally administered from day 2 of DSS treatment in the different dose (10-50 mg/kg body weight). SEM-Ex reduced significantly clinical sign of DSS-induced colitis, including body weight loss, shorten colon length, increased disease activity index (DAI), and histological colon injury. Moreover, SEM-Ex suppressed significantly not only the serum haptoglobin levels and the activities of myeloperoxidase (MPO), but also the colon tissue expression levels of monocyte chemoattractant protein-1 (MCP-1) in DSS-induced mice. In contrast, SEM-Ex increased significantly the colon tissue expression levels of granular colony stimulating factor (G-CSF) well known as anti-inflammatory cytokine. These results suggest that SEM-Ex administration could reduce significantly the clinical signs and regulate of chemokine and anti-inflammatory cytokine in DSS-induced model mice. Therefore, these properties may contribute to the strong anti-ulcerative colitis (UC) response effect of SEM-Ex.