• Journal of Ginseng Research
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• 제39권3호
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• pp.230-237
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• 2015

Background: Colorectal cancer (CRC) is a leading cause of death worldwide. Chronic gut inflammation is recognized as a risk factor for tumor development, including CRC. American ginseng is a very commonly used ginseng species in the West. Methods: A genetically engineered $Apc^{Min/+}$ mouse model was used in this study. We analyzed the saponin composition of American ginseng used in this project, and evaluated its effects on the progression of high-fat-diet-enhanced CRC carcinogenesis. Results: After oral ginseng administration (10-20 mg/kg/d for up to 32 wk), experimental data showed that, compared with the untreated mice, ginseng very significantly reduced tumor initiation and progression in both the small intestine (including the proximal end, middle end, and distal end) and the colon (all p < 0.01). This tumor number reduction was more obvious in those mice treated with a low dose of ginseng. The tumor multiplicity data were supported by body weight changes and gut tissue histology examinations. In addition, quantitative real-time polymerase chain reaction analysis showed that compared with the untreated group, ginseng very significantly reduced the gene expression of inflammatory cytokines, including interleukin-$1{\alpha}$ (IL-$1{\alpha}$), IL-$1{\beta}$, IL-6, tumor necrosis factor-${\alpha}$, granulocyte-colony stimulating factor, and granulocyte-macrophage colony-stimulating factor in both the small intestine and the colon (all p < 0.01). Conclusion: Further studies are needed to link our observed effects to the actions of the gut microbiome in converting the parent ginsenosides to bioactive ginseng metabolites. Our data suggest that American ginseng may have potential value in CRC chemoprevention.

• Asian Pacific Journal of Cancer Prevention
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• 제16권9호
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• pp.3621-3627
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• 2015

Colorectal cancer (CRC) is one of most common causes of cancer-related death worldwide. Recent studies have suggested that microbial and environmental factors including diet and lifestyle can impact on colon cancer development. Vitamin D deficiency and dysfunction of vitamin D receptor (VDR) also correlate with colon cancer. Moreover, leptin, a 16-kDa polypeptide, participates in the regulation of food intake and is associated with other environmental factors affecting colon cancer through the leptin receptor. Altered levels of serum leptin and patterns of expression of its receptor (LPR) may be observed in human colon tumours. Furthermore, the collected data from in vitro and in vivo studies have indicated that consuming probiotic non-pathogenic lactic acid bacteria have beneficial effects on colon cancer. Probiotics, inflammation and vitamin D/VDR have been correlated with leptin and its receptor and are also with colon cancer. Thus, in this paper, we review recent progress on the roles of probiotic, vitamin D/VDR and leptin/LPR in inflammation and colon cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제14권3호
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• pp.1781-1786
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• 2013

Objective: The study was designed to assess the skin and subcutaneous toxicity in patients with advanced colorectal carcinoma treated with four different schedules of FOLFOX. Methods: The patients with histologically confirmed advanced colorectal carcinoma (CRC) were included in the study as per specified inclusion criteria. Toxicity was graded according to CTC v2.0. The frequency of grade 3 and 4 adverse effects were comparatively assessed in each treatment arm. Results: Very severe toxicity was attributed to the FOLFOX7 schedule. The difference between the incidence rate of grade 4 toxicity with all other grades for all parameters of skin and subcutaneous toxicity was highly significant (p=0.00<0.001). Grade 4 hand and foot syndrome was reported only in the FOLFOX7 treatment arm. The most frequent adverse symptom of skin and subcutaneous toxicity reported in the patients treated with modified schedule of FOLFOX was pruritus (grade 1). Frequency and onset of skin and subcutaneous toxic symptoms like alopecia (p=0.000), nail discoloration (p=0.021) and pruritis (p=0.000) was significantly different in each FOLFOX treatment arm. A few cases of oncholysis were also reported in the FOLFOX7 treatment arm. Hand and foot syndrome was fast progressing in patients with grade 1 toxicity. Conclusion: Higher frequency and severity of hand and foot syndrome and pruritus wasa found in the FOLFOX7 treatment arm. Skin and subcutaneous toxicity was comparatively low in the FOLFOX6 treatment arm.

• Asian Pacific Journal of Cancer Prevention
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• 제16권15호
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• pp.6549-6556
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• 2015

The PI3K-Akt-mTOR, $Wnt/{\beta}$-catenin and apoptosis signaling pathways have been shown to be involved in genesis of colorectal cancer (CRC). The aim of this study was to elucidate whether combination of Gelam honey and ginger might have chemopreventive properties in HT29 colon cancer cells by modulating the mTOR, $Wnt/{\beta}$-catenin and apoptosis signaling pathways. Treatment with Gelam honey and ginger reduced the viability of the HT29 cells dose dependently with $IC_{50}$ values of 88 mg/ml and 2.15 mg/ml respectively, their while the combined treatment of 2 mg/ml of ginger with 31 mg/ml of Gelam honey inhibited growth of most HT29 cells. Gelam honey, ginger and combination induced apoptosis in a dose dependent manner with the combined treatment exhibiting the highest apoptosis rate. The combined treatment downregulated the gene expressions of Akt, mTOR, Raptor, Rictor, ${\beta}$-catenin, $Gsk3{\beta}$, Tcf4 and cyclin D1 while cytochrome C and caspase 3 genes were shown to be upregulated. In conclusion, the combination of Gelam honey and ginger may serve as a potential therapy in the treatment of colorectal cancer through inhibiton of mTOR, $Wnt/{\beta}$ catenin signaling pathways and induction of apoptosis pathway.

• BMB Reports
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• 제57권2호
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• pp.110-115
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• 2024

Alterations in DNA methylation play an important pathophysiological role in the development and progression of colorectal cancer. We comprehensively profiled DNA methylation alterations in 165 Korean patients with colorectal cancer (CRC), and conducted an in-depth investigation of cancer-specific methylation patterns. Our analysis of the tumor samples revealed a significant presence of hypomethylated probes, primarily within the gene body regions; few hypermethylated sites were observed, which were mostly enriched in promoter-like and CpG island regions. The CpG Island Methylator Phenotype-High (CIMP-H) exhibited notable enrichment of microsatellite instability-high (MSI-H). Additionally, our findings indicated a significant correlation between methylation of the MLH1 gene and MSI-H status. Furthermore, we found that the CIMP-H had a higher tendency to affect the right-side of the colon tissues and was slightly more prevalent among older patients. Through our methylome profile analysis, we successfully verified the methylation patterns and clinical characteristics of Korean patients with CRC. This valuable dataset lays a strong foundation for exploring novel molecular insights and potential therapeutic targets for the treatment of CRC.

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6669-6672
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• 2013

Colon cancer (CRC) is a serious health problem throughout the world. Development of novel drugs without side effects for this cancer is crucial. Luteolin (LUT), a bioflavonoid, has many beneficial effects such as antioxidant, anti-inflammatory and anti-proliferative potential. was a potent chemical carcinogen used for the induction of colon cancer. Colon carcinogenesis was initiated by intraperitoneal injection of azoxymethane (AOM) to mice at the dose of 15 mg/body kg weight in Balb/C mice for 3 weeks. Mice were treated with LUT at the dose of 1.2 mg/body kg weight orally. Mitochondrial enzymes such as isocitrate dehydrogenase (ICDH), ${\alpha}$-keto dehydrogenase (${\alpha}$-KDH), succinate dehydrogenase (SDH) and the activities of respiratory chain enzymes NADH dehydrogenase and cytochrome c oxidase were found to be elevated in AOM-treated animals. Treatment with LUT decreased the activities of all the parameters significantly. Hence, LUT might be a potent anticancer agent against colorectal cancer.

• Nuclear Medicine and Molecular Imaging
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• 제43권5호
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• pp.429-435
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• 2009

목적: 본 연구의 목적은 대장직장암 간전이 환자에서 수술 전 FDG-PET의 예후인자로서의 중요성을 평가하는 것이다. 대상 및 방법: 진단시부터 간전이를 동반한 대장직장암 환자로서, 수술 전 FDG-PET을 실시하고, 원발병변과 간전이병변에 대한 근치적 수술이 가능했던 24명의 환자 (남자: 여자=14:10; 나이 $63{\pm}10$세)가 연구에 포함되었다. 간전이병변은 13예는 간절제, 7예는 고주파절제술, 그리고 4예는 간절제와 고주파절제술을 함께 시행하였다. 잠재적 예후인자로 원발병변의 최대표준화섭취계수(이하 maxSUV), 간전이병변의 maxSUV, 원발병변/간전이병변의 maxSUV비(M/P ratio), 조직학적인 분화도, 수술 전 CEA, 혈관/림프계/신경 침범여부, T-병기, N-병기, 간전이 병변의 개수, 림프절 전이 개수, 간전이 치료방법을 연구에 포함시켰다. 결과: 24명의 환자 중 14명의 환자가 추적관찰기간 중 재발을 일으켰으며, 이들의 중앙 추적관찰기간은 244일이었다. 추적관찰기간 중 재발을 일으키지 않은 10명 환자의 중앙 추적관찰기간은 504일이었다. 분석에 포함한 잠재적 예후인자 중 M/P ratio만이 재발군($0.72{\pm}0.14$)과 비재발군($0.54{\pm}0.23$)에서 통계적으로 유의한 차이를 보였다(p=0.038). Cox 비례위험 모형을 이용한 생존분석에서 M/P ratio만이 유일하게 통계적으로 유의하게 재발을 예측하는 예후인자였다(상대위험도 37.7, 95% 신뢰구간 2.01-706.1, p=0.016). M/P ratio 0.61을 기준으로 이분하였을 때, 낮은군(<0.61) 11명의 무병생존률은 높은 군(${\geq}0.61$) 13명의 무병생존률에 비해 유의하게 높았다(p=0.026). 결론: 간전이병변/원발병변의 maxSUV 비(M/P ratio)는 간전이를 동반한 대장직장암 환자에서 술 후 재발을 예측하는 예후인자로서 유용하다. 간전이병변의 FDG섭취가 원발병변에 비해 상대적으로 높은 상태는 4병기의 대장직장암 중에서도 더욱 진행된 병기를 나타내는 것으로 보인다.

• The Korean journal of internal medicine
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• 제33권6호
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• pp.1084-1092
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• 2018

Background/Aims: There has been no evidence for the necessity of endoscopy in asymptomatic young men with iron deficiency anemia (IDA). To determine whether endoscopy should be recommended in asymptomatic young men with IDA, we compared the prevalence of gastrointestinal (GI) lesions between young men (< 50 years) with IDA and those without IDA. Methods: We conducted a case-control study on asymptomatic young men aged < 50 years who underwent both esophagogastroduodenoscopy (EGD) and colonoscopy as part of a health checkup between 2010 and 2014. Results: Of 77,864 participants, 128 (0.16%) had IDA and 512 subjects without IDA were matched for several variables including age. Young men with IDA had a significantly higher proportion of colorectal cancer (CRC) (0.8% vs. 0.0%, p = 0.045), villous adenoma (0.8% vs. 0.0%, p = 0.045), and inflammatory bowel disease (IBD; 2.3% vs. 0.4%, p = 0.025) than those without IDA. Additionally, the prevalence of advanced colorectal neoplasia (ACRN) tended to be higher in subjects with IDA than in those without IDA (3.1% vs. 1.0%, p = 0.084). The prevalence of significant lower GI lesions including ACRN and IBD was higher in subjects with IDA than in those without IDA (5.5% vs. 1.4%, p = 0.011). Regarding upper GI lesions, a positive association with IDA was observed only for gastric ulcer (4.7% vs. 1.0%, p = 0.011). Conclusions: GI lesions including CRC, villous adenoma, IBD, and gastric ulcer were more common in asymptomatic young men with IDA. Our results suggest that EGD and particularly colonoscopy should be recommended even in asymptomatic young men with IDA.

• Preventive Nutrition and Food Science
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• 제21권1호
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• pp.57-61
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• 2016

Dietary proteins influence colorectal cancer (CRC) risk, depending on their quantity and quality. Here, using pyrosequencing, we compared the fecal microbiota composition in Balb/c mice fed either a normal protein/carbohydrate diet (ND, 20% casein and 68% carbohydrate) or a high-protein/low-carbohydrate diet (HPLCD, 30% casein and 57% carbohydrate). The results showed that HPLCD feeding for 2 weeks reduced the diversity and altered the composition of the microbiota compared with the ND mice, which included a decrease in the proportion of the family Lachnospiraceae and Ruminococcaceae and increases in the proportions of the genus Bacteroides and Parabacteroides, especially the species EF09600_s and EF604598_s. Similar changes were reported in patients with inflammatory bowel disease, and in mouse models of CRC and colitis, respectively. This suggests that HPLCD may lead to a deleterious luminal environment and may have adverse effects on the intestinal health of individuals consuming such a diet.

• Nutrition Research and Practice
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• 제11권4호
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• pp.281-289
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• 2017

BACKGROUND/OBJECTIVE: The incidence of colorectal cancer (CRC) has been attributed to higher intake of fat and protein. However, reports on the relationship between protein intake and CRC are inconsistent, possibly due to the complexity of diet composition. In this study, we addressed a question whether alteration of protein intake is independently associated with colonic inflammation and colon carcinogenesis. MATERIALS/METHODS: Balb/c mice were randomly divided into 4 experimental groups: 20% protein (control, 20P, 20% casein/kg diet), 10% protein (10P, 10% casein/kg diet), 30% protein (30P, 30% casein/kg diet), and 50% protein (50P, 50% casein/kg diet) diet groups and were subjected to azoxymethane-dextran sodium sulfate induced colon carcinogenesis. RESULTS: As the protein content of the diet increased, clinical signs of colitis including loss of body weight, rectal bleeding, change in stool consistency, and shortening of the colon were worsened. This was associated with a significant decrease in the survival rate of the mice, an increase in proinflammatory protein expression in the colon, and an increase in mucosal cell proliferation. Further, colon tumor multiplicity was dramatically increased in the 30P (318%) and 50P (438%) groups compared with the control (20P) group. CONCLUSIONS: These results suggest that a high protein diet stimulates colon tumor formation by increasing colonic inflammation and proliferation.