• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.2051-2055
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• 2012

Background: The cell cycle checkpoint kinase 2 (CHEK2) gene I157T variant may be associated with an increased risk of colorectal cancer, but it is unclear whether the evidence is sufficient to recommend testing for the mutation in clinical practice. Materials and Methods: We systematically searched PubMed, EMBASES, Elsevier and Springer for relevant articles before Apr 2012. Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using a fixed-effects or random-effects models with Review Manager 5.0 software. Results: A total of seven studies including 4,029 cases and 13,844 controls based on the search criteria were included for analysis. A significant association of the CHEK2 I157T C variant with unselected CRC was found (OR = 1.61, 95% CI = 1.40-1.87, P < 0.001). We also found a significant association with sporadic CRC (OR = 1.48, 95% CI = 1.23-1.77, P < 0.001) and separately with familial CRC (OR = 1.97, 95% CI = 1.41-2.74, P < 0.001). Conclusion: This meta-analysis demonstrates that the CHEK2 I157T variant may be another important CRC-predisposing gene, which increases CRC risk, especially in familial CRC.

• BMB Reports
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• 제41권10호
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• pp.685-692
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• 2008

Colorectal cancer (CRC) is the third most common malignancy in the world. Because CRC develops slowly from removable precancerous lesions, detection of the disease at an early stage during regular health examinations can reduce both the incidence and mortality of the disease. Although sigmoidoscopy offers significant improvements in the detection rate of CRC, its diagnostic value is limited by its high costs and inconvenience. Therefore, there is a compelling need for the identification of noninvasive biomarkers that can enable earlier detection of CRC. Accordingly, many validation studies have been conducted to evaluate genetic, epigenetic or protein markers that can be detected in the stool or in serum. Currently, the fecal-occult blood test is the most widely used method of screening for CRC. However, advances in genomics and proteomics combined with developments in other relevant fields will lead to the discovery of novel non invasive biomarkers whose usefulness will be tested in larger validation studies. Here, non-invasive molecular biomarkers that are currently used in clinical settings and have the potential for use as CRC biomarkers are discussed.

• Molecules and Cells
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• 제45권9호
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• pp.622-630
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• 2022

Colorectal cancer (CRC) has a high mortality rate among cancers worldwide. To reduce this mortality rate, chemotherapy (5-fluorouracil, oxaliplatin, and irinotecan) or targeted therapy (bevacizumab, cetuximab, and panitumumab) has been used to treat CRC. However, due to various side effects and poor responses to CRC treatment, novel therapeutic targets for drug development are needed. In this study, we identified the overexpression of EHMT1 in CRC using RNA sequencing (RNA-seq) data derived from TCGA, and we observed that knocking down EHMT1 expression suppressed cell growth by inducing cell apoptosis in CRC cell lines. In Gene Ontology (GO) term analysis using RNA-seq data, apoptosis-related terms were enriched after EHMT1 knockdown. Moreover, we identified the CHOP gene as a direct target of EHMT1 using a ChIP (chromatin immunoprecipitation) assay with an anti-histone 3 lysine 9 dimethylation (H3K9me2) antibody. Finally, after cotransfection with siEHMT1 and siCHOP, we again confirmed that CHOP-mediated cell apoptosis was induced by EHMT1 knockdown. Our findings reveal that EHMT1 plays a key role in regulating CRC cell apoptosis, suggesting that EHMT1 may be a therapeutic target for the development of cancer inhibitors.

• Biomolecules & Therapeutics
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• 제31권6호
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• pp.655-660
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• 2023

Colorectal cancer (CRC) is one of the most high-risk cancers; however, it has been suggested that estrogen signaling in CRC could have a protective effect. Therefore, we focused on the function of the G protein-coupled estrogen receptor (GPER) among the estrogen receptors in CRC. In this study, we investigated the therapeutic effect of resveratrol via GPER in CRC (RKO and WiDr) cells, CRC cell-derived xenograft models, and organoids (30T and 33T). Resveratrol significantly suppressed cell viability and proliferation in highly GPER-expressing RKO cells compared to that in low GPER-expressing WiDr cells. In xenograft models, resveratrol also delayed tumor growth and exhibited a high survival rate depending on GPER expression in RKO-derived tumors. Furthermore, resveratrol significantly inhibited the viability of organoids with high GPER expression. Additionally, the anticancer effect of resveratrol on CRC showed that resveratrol rapidly responded to GPER, while increasing the expression of p-ERK and Bax and cleaving PARP proteins.

• Asian Pacific Journal of Cancer Prevention
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• 제14권2호
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• pp.909-913
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• 2013

Purpose: The liver is the organ to which colorectal carcinomas (CRCs) most commonly metastasize, and surgical resection has been established as the most effective and potentially curative treatment for CRC with liver metastasis (LM). Therefore, surveillance of LM is vital for improvement of prognosis of CRC patients. In this study, we aimed to explore the potential value of carbohydrate antigen 19-9 (CA 19-9), carcinoembryonic antigen (CEA), and marker enzymes in indicating LM with CRC. Methods: Three groups of eligible patients with metastatic cancers were retrospectively included: CRC patients with LM (CRC-LM) or without LM (CRC-NLM), and non-CRC patients with LM (NCRC-LM). All metastatic lesions were identified by CT or MRI. Data on characteristics of the patients, the primary site, the locations of metastasis, CA 19-9, CEA, and biochemical parameters were collected for analysis. Results: A total of 493 patients were retrospectively included. More alcohol consumption was found in CRC-LM than CRC-NLM. Some biochemical enzymes were found to be significantly higher in groups with LM than without (CRC-LM or NCRC-LM v.s CRC-NLM). Both CEA and CA 19-9 were much higher in CRC-LM than CRC-NLM or NCRC-LM. For CRC patients, CA 19-9, ${\gamma}$-glutamyl transpeptidase, CEA and alcohol consumption were identified as independent factors associated with LM. Conclusion: Our analysis suggested the CA 19-9 might be a potential valuable indicator for LM of CRC in the clinic.

• Asian Pacific Journal of Cancer Prevention
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• 제15권11호
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• pp.4589-4594
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• 2014

The mammalian target of rapamycin (mTOR) signaling pathway is upregulated in the pathogenesis of many cancers, including colorectal cancer (CRC). DEPTOR is an mTOR inhibitor whose expression is negatively regulated by mTOR. However, the role of DEPTOR in the development of CRC is not known. The aim of this study was to investigate the expression of DEPTOR and mTORC1 activity (P-S6) in a subset of CRC patients and determine their relation to tumor differentiation, invasion, nodal metastasis and disease-free survival. Here, Immunohistochemical expression of P-S6 (S235/236) and DEPTOR were evaluated in 1.5 mm tumor cores from 90 CRC patients and in 90 samples of adjacent normal mucosa by tissue microarray. The expression of P-S6 (S235/236) was upregulated in CRC, with the positive rate of P-S6 (S235/236) in CRC (63.3%) significantly higher than that in control tissues (36.7%, 30%) (p<0.05). P-S6 (S235/236) also correlated with high tumor histologic grade (p=0.002), and positive nodal metastasis (p=0.002). In contrast, the expression level of DEPTOR was correlated with low tumor histological grade (p=0.006), and negative nodal metastasis (p=0.001). Interestingly, P-S6 (S235/236) expression showed a significant negative association with the expression of DEPTOR in CRC (p=0.011, R= -0.279). However, upregulation of P-S6 (S235/236) (p=0.693) and downregulation of DEPTOR (p=0.331) in CRC were not significantly associated with overall survival. Thus, we conclude that expression of DEPTOR negatively correlates with mTORC1 activity and tumor progression in CRC. DEPTOR is a potential marker for prognostic evaluation and a target for the treatment of CRC.

• 문화기술의 융합
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• 제6권4호
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• pp.621-626
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• 2020

한국의 대장암 발병율은 점차 증가하고 있으며 대장암 발생은 식생활과 밀접하게 연관이 있는 것으로 보고되고 있다. 대장암 발생에 영향을 미칠 수 있는 식생활 태도 및 영양적 위험요인을 연구하기 위해 대구·경북지역에 거주하는 최근 1년 이내에 대장직장암으로 진단받은 환자 34명과 소화기계 질환이 없는 대조군 51명을 대상으로 식생활태도 및 반정량적 식품섭취빈도조사를 통한 영양섭취상태를 비교 분석하였다. 그 결과, 식사의 규칙성 및 식품섭취의 다양성은 대조군이 대장직장암 환자에 비해 높았으며 대장암 환자는 동식물성 단백질 섭취와 튀긴 음식, 그리고 녹황색 채소 및 과일류의 섭취가 대조군에 비해 높게 나타났다. 영양섭취분석에서는 대장직장암 환자가 대조군에 비해 비타민 A, E, K, C, 나트륨, 마그네슘, 요오드, 콜레스테롤의 섭취량이 유의적으로 높았으며 그 중 비타민 K와 나트륨 섭취는 대장직장암 발생의 위험요인으로 분석되었다. 향후 보다 많은 수의 연구대상자들을 통한 임상연구를 통하여 이들 영양소와 대장직장암 발생과의 상관관계를 확인하고 적절한 영양 교육을 시행한다면 대장직장암 발생의 위험을 예방하는데 도움이 될 것으로 사료된다.

• 한국구조물진단유지관리공학회 논문집
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• 제22권2호
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• pp.161-168
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• 2018

이 연구는 CRC기둥강도곡선의 비탄성영역에 대한 해석적 고찰이다. CRC기둥강도곡선의 비탄성영역은 최대 잔류응력 크기 $0.5{\sigma}_y$와 Bleich이론을 기초로 하고 있다. 이는 실제로 알려진 최대 압축 잔류응력의 크기가 $0.3{\sigma}_y$인 경우 보다 다소 보수적이다. 본 연구는 열압연강재의 최대 압축 잔류응력의 크기를 $0.3{\sigma}_y$으로 고려하여 그에 따른 기둥강도곡선과 접선탄성계수 Et를 제안하고 이를 CRC에서 제안하고 있는 값들과 각각 비교 고찰한다. 축 압축력을 받는 비탄성 기둥의 응력은 기둥에 작용하는 하중이 좌굴을 일으키기 전에 재료의 비례한도를 넘어 항복점에 도달할 것이다. 따라서 점차적인 단면의 항복 상태에 따른 기둥강도곡선을 검토할 필요가 있다. 본 연구는 최대 압축 잔류응력 ${\sigma}_r=0.5{\sigma}_y$을 사용하여 재료의 항복에 따른 임계하중 곡선식을 유도하고 이를 CRC기둥강도곡선과 비교 고찰한다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권6호
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• pp.2397-2402
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• 2015

Previous studies have shown that miR-454 plays an important role in a variety of biological processes in various human cancer cells. However, the underlying mechanisms of this microRNA in colorectal cancer (CRC) cells remain largely unknown. In the present study, we investigated the miR-454 role in CRC cell proliferation. We found that miR-454 expression is markedly upregulated in CRC tissues and CRC cells compared with the matched tumor adjacent tissues and the FHC normal colonic cell line. Ectopic expression of miR-454 promoted the proliferation and anchorage-independent growth of CRC cells, whereas inhibition of miR-454 reduced this effect. Bioinformatics analysis further revealed cylindromatosis (CYLD), a putative tumor suppressor as a potential target of miR-454. Data from luciferase reporter assays showed that miR-454 directly binds to the 3'-untranslated region (3'-UTR) of CYLD mRNA and repressed expression at both transcriptional and translational levels. In functional assays, CYLD-silenced in miR-454-in-transfected SW480 cells have positive effect to promote cell proliferation, suggesting that direct CYLD downregulation is required for miR-454-induced CRC cell proliferation. In sum, our data provide compelling evidence that miR-454 functions as an onco-miRNA, playing a crucial role in the promoting cell proliferation in CRC, and its oncogenic effect is mediated chiefly through direct suppression of CYLD expression.

• Asian Pacific Journal of Cancer Prevention
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• 제15권12호
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• pp.4801-4807
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• 2014

Background: Previous studies have investigated the association between the vitamin D receptor (VDR) BsmI polymorphism and colorectal cancer (CRC) susceptibility, but the results were conflicting. The aim of this study is to quantitatively summarize the relationship between this polymorphism and CRC risk. Materials and Methods: Two investigators independently searched the Medline, Embase, China National Knowledge Infrastructure (CNKI) and Chinese Biomedicine databases for studies published before November 2013. Summary odds ratios (ORs) and 95% confidence intervals (95%CIs) for VDR BsmI polymorphism and CRC were calculated in a fixed-effects model (the Mantel-Haenszel method) and a random-effects model (the DerSimonian and Laird method) when appropriate. Results: This meta-analysis included 14 case-control studies, which included 10,822 CRC cases and 11,779 controls. Overall, the variant genotype (BB) of the BsmI was associated with a lower CRC risk when compared with the wild-type bb homozygote (OR=0.66, 95%CI: 0.49-0.88). Similarly, a decreased CRC risk was also found in the dominant and recessive models. When stratifying for ethnicity, source of controls, and study sample size, associations were observed among Caucasians, population-based studies and studies with large study sample size (>1000 subjects). Limiting the analysis to the studies within Hardy-Weinberg equilibrium, the results were persistent and robust. No publication bias was found in the present study. Conclusions: This updated meta-analysis suggests that the VDR BsmI polymorphism may be associated with a moderate protective effect against CRC.