• Title/Summary/Keyword: Colon cancer model

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Mechanism of Differential Ag-specific Immune Induction by Different Tumor Cell Lysate Pulsed DC (종양 세포 용해액에 따른 수지상세포 유도 항원 특이 면역반응 차이의 기전 연구)

  • Lee, Kang-Eun;Shon, Hye-Jin;Kim, Myung-Joo;Baek, So-Young;Lee, Hyun-Ah
    • IMMUNE NETWORK
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    • v.6 no.3
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    • pp.145-153
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    • 2006
  • Background: Tumor cell lysate has been considered as a preferential antigen source for the therapeutic dendritic cell pulsing. Our experiences with in vivo study with animal tumor model indicate the tumor cell lysate dependent differential effect of DC therapy. Our previous data show that MC38 lysate pulsed-DC induced stronger ag-specific immunity than CT26 lysate pulsed-DC in vitro. In this study we tried to reveal the mechanism for differential induction of ag-specific immunity of different colon cancer cell lysate pulsed-DCs. Methods: MC38 and CT26 cell lines were prepared as lysate by freezing-thawing procedure. Tumor cell antigenicity was confirmed by detecting the surface expression of MHC I/II & B7.1/2 molecules. IL-10, IL-12 and TGF-beta in the tumor cell lysate were detected by ELISA and the presence of heat shock proteins were analysed by western blotting. Results: The secretion of IL-10, a immune-inhibitory cytokine was about 470% higher in CT26 lysate than in MC38. Hsp 70 was detected only in the MC38 lysate but not in the CT26. On the other hand, Hsp 60 and 90 expression were not different in two colon cancer cell lysates. Conclusion: In two different colon cancer cell lysate, immune inhibitory IL-10 (higher in CT26) and Hsp70 (MC38 superiority) were differentially expressed. These data indicate that higher agspecific immunity induction by MC38 lysate pulsed-DC may due to the expression of hsp70 and lower secretion of IL-10, a immune-inhibitory cytokine than CT26 lysate. The significance of other cytokine and the surface marker expression will be discussed.

Induction of Enhancement of Anti-Tumor Immunity by Polysaccharides Fractionated from Acanthopanx Senticosus (가시오가피 다당체에 의한 항종양면역의 유도)

  • Yoon, Taek-Joon;Sung, Ji-Yeon;Yu, Kwang-Won;Lee, Ho;Lee, Kwang-Ho
    • Korean Journal of Pharmacognosy
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    • v.38 no.2 s.149
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    • pp.117-122
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    • 2007
  • The specific activation of the immune system to control cancer growth in vivo has been a long-standing goal in cancer immunology. Whole tumor Iysates have been used either alone or combined with adjuvants to induce specific immune response in vivo. Here, we examined whether freezing/thawing (F/T) colon26-M3.1 tumor cell admixed with EN-3, glycoprotein purified from Acanthopanx Senticosus, could stimulate in vivo immunity by using a murine experimental tumor metastasis model produced by colon26-M3.1 carcinoma cells. Vaccination of mice with F/T treated colon26-M3.1 carcinoma cells in combination with EN-3 as an adjuvant resulted in a significant inhibition in tumor metastasis of mice against live colon26-M3.1 carcinoma challenge. In addition, the splenocytes from vaccinated mice exhibited a higher proliferating activity and secreted interferon-${\gamma}$. These results suggest that EN-3 can be applied to immunoadjuvant to enhance the antitumor immunity in vivo.

Automatic Electronic Cleansing in Computed Tomography Colonography Images using Domain Knowledge

  • Manjunath, KN;Siddalingaswamy, PC;Prabhu, GK
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.18
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    • pp.8351-8358
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    • 2016
  • Electronic cleansing is an image post processing technique in which the tagged colonic content is subtracted from colon using CTC images. There are post processing artefacts, like: 1) soft tissue degradation; 2) incomplete cleansing; 3) misclassification of polyp due to pseudo enhanced voxels; and 4) pseudo soft tissue structures. The objective of the study was to subtract the tagged colonic content without losing the soft tissue structures. This paper proposes a novel adaptive method to solve the first three problems using a multi-step algorithm. It uses a new edge model-based method which involves colon segmentation, priori information of Hounsfield units (HU) of different colonic contents at specific tube voltages, subtracting the tagging materials, restoring the soft tissue structures based on selective HU, removing boundary between air-contrast, and applying a filter to clean minute particles due to improperly tagged endoluminal fluids which appear as noise. The main finding of the study was submerged soft tissue structures were absolutely preserved and the pseudo enhanced intensities were corrected without any artifact. The method was implemented with multithreading for parallel processing in a high performance computer. The technique was applied on a fecal tagged dataset (30 patients) where the tagging agent was not completely removed from colon. The results were then qualitatively validated by radiologists for any image processing artifacts.

Clustering Asian and North African Countries According to Trend of Colon and Rectum Cancer Mortality Rates: an Application of Growth Mixture Models

  • Zayeri, Farid;Sheidaei, Ali;Mansouri, Anita
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.9
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    • pp.4115-4121
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    • 2015
  • Background: Colorectal cancer is the second most common cause of cancer death with half a million deaths per year. Incidence and mortality rates have demonstrated notable changes in Asian and African countries during the last few decades. In this study, we first aimed to determine the trend of colorectal cancer mortality rate in each Institute for Health Metrics and Evaluation (IHME) region, and then re-classify them to find more homogenous classes. Materials and Methods: Our study population consisted of 52 countries of Asia and North Africa in six IHME pre-defined regions for both genders and age-standardized groups from 1990 to 2010.We first applied simple growth models for pre-defined IHME regions to estimate the intercepts and slopes of mortality rate trends. Then, we clustered the 52 described countries using the latent growth mixture modeling approach for classifying them based on their colorectal mortality rates over time. Results: Statistical analysis revealed that males and people in high income Asia pacific and East Asia countries were at greater risk of death from colon and rectum cancer. In addition, South Asia region had the lowest rates of mortality due to this cancer. Simple growth modeling showed that majority of IHME regions had decreasing trend in mortality rate of colorectal cancer. However, re-classification these countries based on their mortality trend using the latent growth mixture model resulted in more homogeneous classes according to colorectal mortality trend. Conclusions: In general, our statistical analyses showed that most Asian and North African countries had upward trend in their colorectal cancer mortality. We therefore urge the health policy makers in these countries to evaluate the causes of growing mortality and study the interventional programs of successful countries in managing the consequences of this cancer.

Investigation of Novel Pharmacological Action of Arctii Fructus and its Compound

  • Hong, Seung-Heon
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2018.04a
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    • pp.9-9
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    • 2018
  • Arctii Fructus (AF), which contains arctigenin (ARC) as a major constituent, is traditionally used as an anti-inflammatory medicine to treat inflammatory sore throat. Although several studies have proven its anti-inflammatory effects, there have been no reports on its use in inflammation related disorders such as obesity, cancer metastasis, and allergic responses. This study investigated the anti-obesity effect and anti-metastasis effect of AF and ARC. AF and ARC inhibited weight gain by reducing the mass of white adipose tissue in high fat diet (HFD)-induced obese mice. Serum cholesterol levels were also improved by AF and ARC. In in vitro experiments, AF and ARC decreased differentiation of white adipocytes. Furthermore, AF induced differentiation of brown adipocytes, which are able to consume surplus energy through non-shivering thermogenesis. Also, AF and ARC inhibited colon cancer and lung metastasis of colon cancer. They suppressed not only colorectal cancer cell progression by inhibiting cell growth, but also prohibited lung metastasis by regulating epithelial-mesenchymal transition (EMT), migration, and the invasion. These effects were confirmed in an experimental metastasis mouse model. In addition, AF and ARC inhibited mast cell mediated allergic responses. Collectively, our study suggests that AF and ARC might show inhibitory effects on inflammation related diseases, including obesity, cancer, cancer metastasis, and allergic responses.

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Markov's Modeling for Screening Strategies for Colorectal Cancer

  • Barouni, Mohsen;Larizadeh, Mohammad Hassan;Sabermahani, Asma;Ghaderi, Hossien
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.10
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    • pp.5125-5129
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    • 2012
  • Economic decision models are being increasingly used to assess medical interventions. Advances in this field are mainly due to enhanced processing capacity of computers, availability of specific software to perform the necessary tasks, and refined mathematical techniques. We here estimated the incremental cost-effectiveness of ten strategies for colon cancer screening, as well as no screening, incorporating quality of life, noncompliance and data on the costs and profit of chemotherapy in Iran. We used a Markov model to measure the costs and quality-adjusted life expectancy of a 50-year-old average-risk Iranian without screening and with screening by each test. In this paper, we tested the model with data from the Ministry of Health and published literature. We considered costs from the perspective of a health insurance organization, with inflation to 2011, the Iranian Rial being converted into US dollars. We focused on three tests for the 10 strategies considered currently being used for population screening in some Iranians provinces (Kerman, Golestan Mazandaran, Ardabil, and Tehran): low-sensitivity guaiac fecal occult blood test, performed annually; fecal immunochemical test, performed annually; and colonoscopy, performed every 10 years. These strategies reduced the incidence of colorectal cancer by 39%, 60% and 76%, and mortality by 50%, 69% and 78%, respectively, compared with no screening. These approaches generated ICER (incremental cost-effectiveness ratios) of $9067, $654 and $8700 per QALY (quality-adjusted life year), respectively. Sensitivity analyses were conducted to assess the influence of various scales on the economic evaluation of screening. The results were sensitive to probabilistic sensitivity analysis. Colonoscopy every ten years yielded the greatest net health value. Screening for colon cancer is economical and cost-effective over conventional levels of WTP8.

Protective Role of Aspirin, Vitamin C, and Zinc and their Effects on Zinc Status in the DMH-Induced Colon Carcinoma Model

  • Christudoss, Pamela;Selvakumar, Ratnasamy;Pulimood, Anna Benjamin;Fleming, Jude Joseph;Mathew, George
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.8
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    • pp.4627-4634
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    • 2013
  • Chemoprotection refers to the use of specific natural or synthetic chemical agents to suppress or prevent the progression to cancer. The purpose of this study is to assess the protective effect of aspirin, vitamin C or zinc in a dimethyl hydrazine (DMH) colon carcinoma model in rats and to investigate the effect of these supplements on changes associated with colonic zinc status. Rats were randomly divided into three groups, group 1 (aspirin), group 2 (vitamin C) and group 3 (zinc), each being subdivided into two groups and given subcutaneous injection of DMH (30 mg/kg body wt) twice a week for 3 months and sacrificed at 4 months (A-precancer model) and 6 months (B-cancer model). Groups 1, 2, 3 were simultaneously given aspirin, vitamin C, or zinc supplement respectively from the beginning till the end of the study. It was observed that 87.5% of rats co-treated with aspirin or vitamin C showed normal colonic histology, along with a significant decrease in colonic tissue zinc at both time points. Rats co-treated with zinc showed 100% reduction in tumor incidence with no significant change in colonic tissue zinc. Plasma zinc, colonic CuZnSOD (copper-zinc superoxide dismutase) and alkaline phosphatase activity showed no significant changes in all 3 cotreated groups. These results suggest that aspirin, vitamin C or zinc given separately, exert a chemoprotective effect against chemically induced DMH colonic preneoplastic progression and colonic carcinogenesis in rats. The inhibitory effects are associated with maintaining the colonic tissue zinc levels and zinc enzymes at near normal without significant changes.

Walnut phenolic extracts reduce telomere length and telomerase activity in a colon cancer stem cell model

  • Shin, Phil-Kyung;Zoh, Yoonchae;Choi, Jina;Kim, Myung-Sunny;Kim, Yuri;Choi, Sang-Woon
    • Nutrition Research and Practice
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    • v.13 no.1
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    • pp.58-63
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    • 2019
  • BACKGROUND/OBJECTIVES: Telomeres are located at the chromosomal ends and progressively shortened during each cell cycle. Telomerase, which is regulated by hTERT and c-MYC, maintains telomeric DNA sequences. Especially, telomerase is active in cancer and stem cells to maintain telomere length for replicative immortality. Recently we reported that walnut phenolic extract (WPE) can reduce cell viability in a colon cancer stem cell (CSC) model. We, therefore, investigated the effect of WPE on telomere maintenance in the same model. MATERIALS AND METHODS: $CD133^+CD44^+$ cells from HCT116, a human colon cancer cell line, were sorted by Fluorescence-activated cell sorting (FACS) and treated with WPE at the concentrations of 0, 10, 20, and $40{\mu}g/mL$ for 6 days. Telomere lengths were assessed by quantitative real-time PCR (qRT-PCR) using telomere specific primers and DNA extracted from the cells, which was further adjusted with single-copy gene and reference DNA ($ddC_t$). Telomerase activity was also measured by qRT-PCR after incubating the PCR mixture with cell protein extracts, which was adjusted with reference DNA ($dC_t$). Transcriptions of hTERT and c-MYC were determined using conventional RT-PCR. RESULTS: Telomere length of WPE-treated cells was significantly decreased in a dose-dependent manner ($5.16{\pm}0.13$ at $0{\mu}g/mL$, $4.79{\pm}0.12$ at $10{\mu}g/mL$, $3.24{\pm}0.08$ at $20{\mu}g/mL$ and $3.99{\pm}0.09$ at $40{\mu}g/mL$; P = 0.0276). Telomerase activities concurrently decreased with telomere length ($1.47{\pm}0.04$, $1.09{\pm}0.01$, $0.76{\pm}0.08$, and $0.88{\pm}0.06$; P = 0.0067). There was a positive correlation between telomere length and telomerase activity (r = 0.9090; P < 0.0001). Transcriptions of both hTERT and c-MYC were also significantly decreased in the same manner. CONCLUSION: In the present cell culture model, WPE reduced telomere maintenance, which may provide a mechanistic link to the effect of walnuts on the viability of colon CSCs.

Potentiating Dietary Green Tea Extracts Anti-Tumor Activity of Cisplatin in BALB/c Mice Bearing CT26 Colon Carcinoma (대장암(CT 26) 생쥐에서 녹차추출물 음용에 의한 시스플라틴 항암작용 증강효과)

  • Lee, Byoung-Rai;Park, Pyoung-Sim
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.41 no.8
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    • pp.1100-1105
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    • 2012
  • Green tea intake is known to have preventive effects against cancer. In this study, we evaluated the tumor suppressive effects of dietary green tea extracts (GTE) as a modulator on cisplatin in an established colon cancer mouse model. The cisplatin-induced cytotoxicity was determined with cell viability of the mouse colon cancer cell line (CT26) in vitro. The influence of GTE on the anti-tumor activity of cisplatin was evaluated by measuring tumor size with digital calipers in mice bearing CT26 colon carcinomas. The CT26 cell viability decreased to 93% at a $20{\mu}g/mL$ concentration of cisplatin. However, cell viability decreased to 15% with a combination of $20{\mu}g/mL$ cisplatin and GTE ($75{\mu}g/mL$). There were no apparent changes in cisplatin-induced cytotoxicity with GTE and epigallocathechin gallate (EGCG) treatments. Tumor size decreased in dietary GTE combining intra-peritoneal cisplatin-injected tumors bearing mice compared with cisplatin or GTE alone administered to tumor-bearing mice. These experiments showed that dietary GTE has a potentiating effect on the cisplatin anti-tumor activity of an established mice colon cancer model. Therefore, the GTE may be a candidate for modulators in anticancer treatments with cisplatin.

Growth of Human Colon Cancer Cells in Nude Mice is Delayed by Ketogenic Diet With or Without Omega-3 Fatty Acids and Medium-chain Triglycerides

  • Hao, Guang-Wei;Chen, Yu-Sheng;He, De-Ming;Wang, Hai-Yu;Wu, Guo-Hao;Zhang, Bo
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.5
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    • pp.2061-2068
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    • 2015
  • Background: Tumors are largely unable to metabolize ketone bodies for energy due to various deficiencies in one or both of the key mitochondrial enzymes, which may provide a rationale for therapeutic strategies that inhibit tumor growth by administration of a ketogenic diet with average protein but low in carbohydrates and high in fat. Materials and Methods: Thirty-six male BALB/C nude mice were injected subcutaneously with tumor cells of the colon cancer cell line HCT116. The animals were then randomly split into three feeding groups and fed either a ketogenic diet rich in omega-3 fatty acids and MCT (MKD group; n=12) or lard only (LKD group; n=12) or a standard diet (SD group; n=12) ad libitum. Experiments were ended upon attainment of the target tumor volume of $600mm^3$ to $700mm^3$. The three diets were compared for tumor growth and survival time (interval between tumor cell injection and attainment of target tumor volume). Results: The tumor growth in the MKD and LKD groups was significantly delayed compared to that in the SD group. Conclusions: Application of an unrestricted ketogenic diet delayed tumor growth in a mouse xenograft model. Further studies are needed to address the mechanism of this diet intervention and the impact on other tumor-relevant parameters such as invasion and metastasis.