• 제목/요약/키워드: Colon Cancer

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암 진단 분자 마커로서 이동성 유전인자의 응용 (Application of Transposable Elements as Molecular-marker for Cancer Diagnosis)

  • 김혜민;김정안;우효정;홍정현;김진엽;김희수
    • 생명과학회지
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    • 제27권10호
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    • pp.1215-1224
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    • 2017
  • 현재까지 다양한 암의 발병 원인이 밝혀졌는데, 그 중 하나로써 DNA에 돌연변이가 축적되어 유전체가 불안정 해짐에 따라 암이 발생될 수 있는 기작들이 주목받고 있다. 생물정보학과 유전체학의 발달에 따라 질병 연구에 있어서 보다 더 정확하고 신뢰성 있는 바이오마커를 찾는 것이 가능해졌다. 따라서, 생물정보학과 유전체학의 연구 기반을 바탕으로 한 암의 바이오마커는 암의 조기진단뿐만 아니라, 더 나아가 암 발생 예측과 암환자의 예후 진단에 적용될 수 있다. 최근 들어 인간 유전체에서 약 45%를 차지하는 이동성 유전인자(transposable elements, TEs)가 유전자의 발현 조절과 DNA의 돌연변이를 유도함으로써 다양한 질병에 영향을 미친다는 사실이 밝혀짐에 따라, 이러한 이동성 유전인자들이 암의 발생과 어떤 연관이 있는지에 대한 연구 또한 활발히 진행되고 있다. 따라서 우리는 이동성 유전인자가 대장암과 어떤 연관성이 있는지에 대해 조사를 하였으며, 이를 어떻게 바이오마커로 활용할 수 있는지 알아보았다. 우선, 이동성 유전인자 중 인간 유전체에 많이 존재하면서 유전체에 많은 영향을 미치는 LINE-1 (long interspersed nuclear element-1, L1)과 Alu, LTR (long terminal repeat) 위주로 확인하였다. 흥미롭게도, 대장암 세포에서 LINE-1의 저메틸화, APC 유전자 내에 LINE-1 삽입, Alu의 저메틸화와 과메틸화, LTR 삽입에 따른 isoform 발생 등이 특징적으로 나타나는 것을 알 수 있었다. 또한 원발암유전자에서의 L1 저메틸화가 대장암 전이의 바이오마커로 쓰일 수 있다는 것과 Alu에 의한 MLH1 돌연변이가 가족성 및 유전성 대장암에서 흔히 발견된다는 것을 알 수 있었다. 이 때 이동성 유전인자에 의하여 영향 받는 유전자들의 발현을 in silico 발현 분석을 통하여 분석하였으며, 조직별, 성별 특이적 발현 양상을 제시하였다. 이들을 토대로 대장암 바이오마커를 개발하여 유전성 대장암의 예측 및 대장암 진단 또는 대장암 예후 예측을 통한 개인 맞춤형 치료에 활용할 수 있을 것으로 예상된다.

Preventive and Therapeutic Roles of Ginseng - Focus on Colon Cancer

  • Vayghan, Hamed Jafari;Ghadimi, Sevda Saleh;Nourazarian, Ali Reza
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권2호
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    • pp.585-588
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    • 2014
  • Colorectal cancer is one of the most prevalent diseases all over the world. Early screening and start of chemotherapy is effective in decreasing mortality. This type of cancer can be controlled to some extent via a healthy diet rich in fruit and vegetables. Ginseng is a plant which has been consumed as a herbal medicine for thousands of years in Asian countries. Several in vitro and in vivo studies have shown that this plant not only reduces the incidence of colorectal cancer, but also improves patient's status by enhancing the effects of chemotherapy drugs. However, further studies are needed to prove this relationship. We briefly review ginseng and its components such as ginsenosides reported anticancer effects and their mechanisms of action. Understanding these relationships may produce insights into chemical and pharmacological approaches for enhancing the chemo preventive effects of ginsenosides and for developing novel anticancer agents.

Conjugated Linoleic Acid (CLA)가 인체 대장암 세포주에서 Matrix Metalloproteinase (MMP) 활성과 세포이동성에 미치는 영향 (Effects of Conjugated Linoleic Acid (CLA) on Matrix Metalloproteinase (MMP) Activity and Cell Motility in Human Colon Cancer Cell Lines)

  • 설소미;방명희;최옥숙;윤정한;김우경
    • Journal of Nutrition and Health
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    • 제36권3호
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    • pp.280-286
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    • 2003
  • Conjugated linoleic acid (CLA) consists of several geometric isomers of linoleic acid. CLA is found in foods derived from ruminants and exhibits strong anticarcinogenic effects in a variety of animal models. Matrix metalloproteinases (MMPs) play a key role in cancer progression. Specifically, MMP-2 and -9, which hydrolyze the basal membrane type IV collagen, are involved in the initial breakdown of collagen and basement membrane components during tumor growth and invasion. However, the effects of CLA on cancer cell motility and MMP expression and activity are not currently well known. Therefore, the present study examined whether CLA reduces the activity of MMP and cell motility in SW480 and SW620 cells, the human colon cancer cell lines. Gelatin zymography and Western blot analysis revealed that phorbol 12-myristate 13-acetate (PMA) induced the activity and protein expression of Mr 92,000 MMP-9 in both cell lines. To examine whether CLA inhibits the MMP activity, cells were incubated with 100 ngfmL PMA in the presence of various concentrations of CLA. PMA-induced MMP-9 activity was decreased by 20 $\mu$ M CLA in SW480 cells, and by 10 $\mu$ M and 20 $\mu$ M CLA in SW620 cells. Results from the Hoyden chamber assay showed that cell motility was increased by PMA and that PMA-induced cell motility was significantly decreased by 20 $\mu$ M CLA in SW480 cells. These results indicate that CLA may reduce the motility and MMP activity in human colon cancer cells.

Induction of Apoptosis and Autophagy by Resveratrol via Activation of AMPK Pathway in 5-Fluorouracil-Resistant Colon Cancer Cells

  • Lee, Seung Young;Jung, Ji Young;Choi, Hee Won;Choi, Kyung Min;Jeong, Jin-Woo
    • 한국자원식물학회:학술대회논문집
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    • 한국자원식물학회 2018년도 추계학술대회
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    • pp.101-101
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    • 2018
  • Resveratrol is a polyphenolic compound, which is a naturally occurring phytochemical and is found in a variety of plants, including food such as grapes, berries and peanuts. Although several studies have demonstrated that resveratrol possesses anti-cancer activity against various types of human cancer, the molecular mechanisms of resveratrol-mediated overcome drug resistance potential are unclear. In this study, we determined whether resveratrol attenuates drug resistance responses in 5-fluorouracil-resistant colon cancer (SNUC5/5-FUR) cells. Treatment with resveratrol significantly enhanced apoptosis in a concentration-dependent manner, which was associated with the modulation of anti- and/or pro-apoptotic protein expression, activation of caspases and activation of AMP-activated protein kinase. Resveratrol treatment also increased the induction of autophagy through up-regulation of autophagy-related genes such as Microtubule-associated protein 1A/1B-light chain 3, P62 and beclin-1. However, blocking of autophagy by bafilomycin A1 reduced apoptotic cell death, suggesting that resveratrol-induced autophagy functions as a cell death mechanism in SNUC5/5-FU cells. Although the further studies are needed, these findings suggest that resveratrol may have therapeutic potential to overcome drug resistance in colon cancer patients.

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MiR-133b Acts as a Tumor Suppressor and Negatively Regulates TBPL1 in Colorectal Cancer Cells

  • Xiang, Kai-Min;Li, Xiao-Rong
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권8호
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    • pp.3767-3772
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    • 2014
  • Introduction: MicroRNAs have emerged as post-transcriptional regulators that are critically involved in tumorigenesis. This study was designed to explore the effect of miRNA 133b on the proliferation and expression of TBPL1 in colon cancer cells. Methods: Human colon cancer SW-620 cells and human colon adenocarcinoma HT-29 cells were cultured. MiRNA 133b mimcs, miRNA 133b inhibitors, siRNA for TBPL1 and scrambled control were synthesized and transfected into cells. MiR-133b levels in cells and CRC tumor tissue was measured by real-time PCR. TBPL1 mRNA was detected by RT-PCR. Cell proliferation was studied with MTT assay. Western blotting was applied to detect TBPL1 protein levels. Luciferase assays were conducted using a pGL3-promoter vector cloned with full length of 3'UTR of human TBPL1 or 3'UTR with mutant sequence of miR-133b target site in order to confirm if the putative binding site is responsible for the negative regulation of TBPL1 by miR-133b. Results: Real time PCR results showed that miRNA 133b was lower in CRC tissue than that in adjacent tissue. After miR-133b transfection, its level was elevated till 48h, accompanied by lower proliferation in both SW-620 and HT-29 cells. According to that listed in http://www.targetscan.org, the 3'-UTR of TBPL1 mRNA (NM_004865) contains one putative binding site of miR-133b. This site was confirmed to be responsible for the negative regulation by miR-133b with luciferase assay. Further, Western blotting and immunohistochemistry both indicated a higher TBPL1 protein expression level in CRC tissue. Finally, a siRNA for TBPL1 transfection obviously slowed down the cell proliferation in both SW-620 and HT-29 cells. Conclusion: MiR-133b might act as a tumor suppressor and negatively regulate TBPL1 in CRC.

Functional Analysis of B7-H3 in Colonic Carcinoma Cells

  • Lu, Peng;Liu, Rong;Ma, Er-Min;Yang, Tie-Jian;Liu, Jia-Lin
    • Asian Pacific Journal of Cancer Prevention
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    • 제13권8호
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    • pp.3899-3903
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    • 2012
  • B7-H3 is a newly discovered member of the B7/CD28 superfamily which functions as an important T-cell immune molecule. It has been reported recently that B7-H3 is highly expressed in many cancer cells, the data indicating that it may be a regulation factor contributing to tumor-resistance. In our study, we used bioinformatics to identify differentially expressed genes between colonic cancer cells and normal colonic cells, aiming to analyze mechanisms and identify sub-pathways closely related to progression, with the final aim of finding small molecule drugs which might interfere this progression. We found that ajmaline is one related factor which may enhance self-immunity in colon carcinoma therapy and B7-H3 plays important roles with regard to immunoreactions of colonic cancer cells. All the results indicate that H7-B3 is a favorable prognostic biomarker for colon carcinomas, providing novel information regarding likely targets for intervention.

인천광역시 국가암검진 홍보방법과 수검률의 관련성 (The Relationship between Cancer Screening Rates and Promotional Methods in Incheon Metropolitan City)

  • 김종두
    • 보건행정학회지
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    • 제26권4호
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    • pp.382-389
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    • 2016
  • Background: National cancer screening reduces mortality from stomach, colon, breast, and cervical cancer. However, cancer screening rates remain lower than 50% in Korea. This research was designed to make effective guidelines for cancer screening promotion to increase participation rate in cancer screening. Methods: Data was collected from Incheon regional cancer center's telephone survey 'Recognition of cancer prevention and control' of 861 Incheon citizens over age 40. Logistic regression was used to analyse a relationships between cancer screening rates and promotional methods. PASW SPSS ver. 18.0 program (SPSS Inc., Chicago, IL, USA) was used for statistical analysis. Results: About 27.4% of respondents (236 of 861 respondents) have recognized the promotional program of Incheon regional cancer center for cancer screening participation. Cancer screening rate was associated with age group, educational level for stomach cancer, age group, bus advertisement (odds ratio, 1.19 to 2.75) for colon cancer, educational level, residential area for breast cancer, and age group for cervical cancer. Conclusion: There was relationship between stomach cancer screening rates and promotional methods. Therefore, cancer screening promotion guidelines to increase participation rate should be considered.

Effects of Lactic Acid Bacteria on intestinal Microbial Enzyme Activity and Composition in Rats Treated with Azoxymethane

  • Sang-Myeong;Lee, Wan-Kyu
    • Journal of Microbiology
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    • 제39권3호
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    • pp.154-161
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    • 2001
  • In recent years, colon cancer has been reported to be one of the most important causes of cancer morbidity and mortality in Korea. Epidemiological and experimental studies suggest that lactic acid bacteria (LAB) used to ferment dairy products inhibits colon carcinogenesis. The present study was designed to determine whether the colon cancer inhibitory effect of LAB (Bifidobacterium longum Hy8001; Bif and Lactobacillus acidophilus HY2l04; Lac) of Korean origin, is associated with intestinal microflora composition and certain enzyme activity in rats treated with azoxymethane (AOM). At five weeks of age, SD rats were divided at random into four (AOM alone, Bif, Lac, and Bif+Lac) groups. Oral administration of lactic acid bacteria cultures were performed daily until the termination of the study. Two weeks later all animals were given a subcutaneous injection of AOM dissolved in normal saline at a dose of 15 mg/kg of body weight once weekly for 2 weeks. Every two weeks for 10 weeks, five of the rats in each group were randomly chosen for fecal specimen collection. The fecal specimens were used for assay of $\beta$-glucuronidase and nitroreductase, and analysis of intestinal microflora composition. The activity of $\beta$-glucuronidase which plays an important role in the production of the carcinogenic metabolite of azoxymethane was remarkably increased in the AOM alone group after AOM injection and maintained the high level during the experiment. However, LAB inhibited the AOM-induced increase in $\beta$-glucuronidase activity. Nitroreductase activity decreased by 30-40% in LAB treated groups in comparison with that of the AOM alone group. The results of the present study suggest that LAB inhibits colon carcinogenesis by modulating the metabolic activity of intestinal micro-flora and improving the composition of intestinal microflora.

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암 조기발견 지식.암발생 위험성 지각과 암 조기검진 수검 여부와의 관계: 40세 이상 일반인 대상으로 (Relationships between Knowledge about Early Detection, Cancer Risk Perception and Cancer Screening Tests in the General Public Aged 40 and Over)

  • 양영희
    • 종양간호연구
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    • 제12권1호
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    • pp.52-60
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    • 2012
  • Purpose: This study is to determine knowledge about early detection and risk perception of cancer according to taking cancer screening tests in the general population. Methods: The participants were 151 people aged 40 years or older. A questionnaire consisted of knowledge about early detection (warning signs, cancer screening methods, general knowledge for early detection), cancer risk perception and history of cancer screening during past 2 years. Results: The percentages of correct answers were 64.7% in knowledge about warning signs, 73.7% in knowledge of cancer screening tests and 80.1% in general knowledge for early detection. Participants had the highest knowledge about screening methods for stomach cancer and the lowest for liver and colon cancer. The level of risk perception was medium. The participants who participated in cancer screening showed lower risk perception than those who did not. There was no significant relationship between knowledge and performance of cancer screening. The primary reason for not participating in cancer screening was patient's perception of their own health. Conclusion: These results suggest that cancer risk perception can affect the performance of cancer screening and we need to study how to handle this problem. Additionally screening programs should focus on liver cancer and colon cancer.