• Title/Summary/Keyword: Colorectal Cancer

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A Study on Clinical Decision Support System based on Common Data Model (공통데이터모델 기반의 임상의사결정지원시스템에 관한 연구)

  • Ahn, Yoon-Ae;Cho, Han-Jin
    • Journal of the Korea Convergence Society
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    • v.10 no.11
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    • pp.117-124
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    • 2019
  • Recently, medical IT solutions are being provided on a distributed environment basis. In Korea, the necessity of developing a clinical decision support system that can share medical information in a distributed environment has been recognized and studied. The existing clinical decision support system is being built using only medical information of its own within the hospital. This makes it difficult for existing systems to achieve good results in terms of efficiency and accuracy of decision support. In order to solve these limitations, this paper proposes a design and implementation method of clinical decision support system based on common data model in medical field. To explain the application process of the proposed model, we describe the development scenario of the clinical decision support system for the diagnosis of colorectal cancer. We also propose the essential requirements for the development of successful clinical decision support systems. Through this, it is expected that it will be possible to develop clinical decision support system that can be used in various hospitals and improve the efficiency and accuracy of the system.

Effects of red ginseng on gut, microbiota, and brain in a mouse model of post-infectious irritable bowel syndrome

  • Yu, Seonhye;Chun, Eunho;Ji, Yeounjung;Lee, Young Joo;Jin, Mirim
    • Journal of Ginseng Research
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    • v.45 no.6
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    • pp.706-716
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    • 2021
  • Background: Irritable bowel syndrome (IBS), the most common functional gastrointestinal disorder, is characterized by chronic abdominal pain and bowel habit changes. Although diverse complicated etiologies are involved in its pathogenesis, a dysregulated gut-brain axis may be an important factor. Red ginseng (RG), a traditional herbal medicine, is proven to have anti-inflammatory effects and improve brain function; however, these effects have not been investigated in IBS. Methods: Three-day intracolonic zymosan injections were used to induce post-infectious human IBS-like symptoms in mice. The animals were randomized to receive either phosphate-buffered saline (CG) or RG (30/100/300 mg/kg) for 10 days. Amitriptyline and sulfasalazine were used as positive controls. Macroscopic scoring was performed on day 4. Visceral pain and anxiety-like behaviors were assessed by colorectal distension and elevated plus maze and open field tests, respectively, on day 10. Next-generation sequencing of gut microbiota was performed, and biomarkers involved in gut-brain axis responses were analyzed. Results: Compared to CG, RG significantly decreased the macroscopic score, frequency of visceral pain, and anxiety-like behavior in the IBS mice. These effects were comparable to those after sulfasalazine and amitriptyline treatments. Moreover, RG significantly increased the proliferation of beneficial microbes, including Lactobacillus johnsonii, Lactobacillus reuteri, and Parabacteroides goldsteinii. RG significantly suppressed expression of IL-1β and c-fos in the gut and prefrontal cortex, respectively. Further, it restored the plasma levels of corticosterone to within the normal range, accompanied by an increase in adrenocorticotropic hormone. Conclusion: RG may be a potential therapeutic option for the management of human IBS.

Differential effects of various dietary proteins on dextran sulfate sodium-induced colitis in mice

  • Eunyeong, Ahn;Hyejin, Jeong;Eunjung, Kim
    • Nutrition Research and Practice
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    • v.16 no.6
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    • pp.700-715
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    • 2022
  • BACKGROUND/OBJECTIVES: Chronic colitis is a risk factor for colorectal cancer (CRC) development in both animals and humans. Previously, we reported that a diet rich in protein (with casein as the protein source) significantly increased the risk of mouse CRC development in a dose-dependent manner. In this study, we investigated the effects of different protein sources on the risk of colitis development. MATERIALS/METHODS: Balb/c mice were divided into 7 experimental groups: 20% casein (20C), 20C-dextran sulfate sodium (DSS), 40% casein-DSS (40CD), 40% whey protein-DSS (40WD), 40% soy protein-DSS (40SD), 40% white meat-DSS (40WMD), and 40% red meat-DSS (40RMD). Mice were fed an experimental diet for 4 wk and received 3% DSS in their drinking water for 6 days during the 4th wk of the experimental period. RESULTS: Compared to other groups, the 40CD group showed the most aggravated colitis with increased disease activity and inflammatory markers. In the 40RMD group, interleukin (IL)-6 levels were the highest among all the groups. The 40SD group showed conflicting effects, for example, elevated mortality and disease activity but decreased nitric oxide (NO) levels. The 40WD group showed attenuated colitis with increased IL-10 levels and decreased NO levels. The 40WMD group showed conflicting effects, including decreased NO levels and elevated fecal lipocalin-2 and IL-6 levels. CONCLUSIONS: These results suggest that, at levels of 40% in the diet, casein and red meat exacerbate colitis, whereas whey protein mitigates it the most effectively.

A Synthetic Analog of Resveratrol Inhibits the Proangiogenic Response of Liver Sinusoidal Cells during Hepatic Metastasis

  • Olaso, Elvira;Benedicto, Aitor;Lopategi, Aritz;Cossio, Fernando P.;Arteta, Beatriz
    • Biomolecules & Therapeutics
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    • v.30 no.2
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    • pp.162-169
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    • 2022
  • We utilized Fas21, a resveratrol analog, to modulate the function of hepatic stellate cells (HSCs) and liver sinusoidal endothelial cells (LSECs) during the angiogenic phase of murine liver metastasis by B16 melanoma and 51b colorectal carcinoma. Preangiogenic micrometastases were treated with Fas21 (1 mg/kg/day) or vehicle during the development of intra-angiogenic tracts. Mice treated with Fas21 showed reduced liver tumor foci in both liver metastasis models. Micrometastases were classified immunohistochemically, as well as according to their position coordinates and connection to local microvasculature. The volume of liver occupied by sinusoidal-type foci, containing infiltrating angiogenic capillaries, decreased by ~50% in Fas21-treated mice compared to vehicle-treated ones in both tumor metastasis models. The volume of portal foci, containing peripheral neoangiogenesis within a discontinuous layer of myofibroblasts, was similar in all experimental groups in both tumor metastasis models, but displayed enhanced necrotic central areas devoid of angiogenesis following Fas21 treatment. As a result, sinusoidal tumors from mice treated with Fas21 showed a 50% reduction in desmin(+)/asma(+) HSCs and CD31(+) vessel density, and a 45% reduction in intrametastatic VEGF mRNA compared with sinusoidal tumors from vehicle-treated mice. Necrotic portal metastases increased 2-4-fold in treated mice. In vitro, Fas21 reduced VEGF secretion by HSCs and 51b cells dose-dependently. Additionally, HSCs migration in response to tumor soluble factors was dose-dependently diminished by Fas21, as was LSEC migration in response to HSCs and tumor soluble factors. Resveratrol analog Fas21 inhibits the proangiogenic response of HSCs and LSECs during the development of murine liver metastasis.

The Carcinogenic Liver Fluke Opisthorchis viverrini is a Reservoir for Species of Helicobacter

  • Deenonpoe, Raksawan;Chomvarin, Chariya;Pairojkul, Chawalit;Chamgramol, Yaowalux;Loukas, Alex;Brindley, Paul J;Sripa, Banchob
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.5
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    • pp.1751-1758
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    • 2015
  • There has been a strong, positive correlation between opisthorchiasis-associated cholangiocarcinoma and infection with Helicobacter. Here a rodent model of human infection with Opisthorchis viverrini was utilized to further investigate relationships of apparent co-infections with O. viverrini and H. pylori. A total of 150 hamsters were assigned to five groups: i) Control hamsters not infected with O. viverrini; ii) O. viverrini-infected hamsters; iii) non-O. viverrini infected hamsters treated with antibiotics (ABx); iv) O. viverrini-infected hamsters treated with ABx; and v) O. viverrini-infected hamsters treated both with ABx and praziquantel (PZQ). Stomach, gallbladder, liver, colonic tissue, colorectal feces and O. viverrini worms were collected and the presence of species of Helicobacter determined by PCR-based approaches. In addition, O. viverrini worms were cultured in vitro with and without ABx for four weeks, after which the presence of Helicobacter spp. was determined. In situ localization of H. pylori and Helicobacter-like species was performed using a combination of histochemistry and immunohistochemistry. The prevalence of H. pylori infection in O. viverrini-infected hamsters was significantly higher than that of O. viverrini-uninfected hamsters ($p{\leq}0.001$). Interestingly, O. viverrini-infected hamsters treated with ABx and PZQ (to remove the flukes) had a significantly lower frequency of H. pylori than either O. viverr-iniinfected hamsters treated only with ABx or O. viverrini-infected hamsters, respectively ($p{\leq}0.001$). Quantitative RT-PCR strongly confirmed the correlation between intensity H. pylori infection and the presence of liver fluke infection. In vitro, H. pylori could be detected in the O. viverrini worms cultured with ABx over four weeks. In situ localization revealed H. pylori and other Helicobacter-like bacteria in worm gut. The findings indicate that the liver fluke O. viverrini in the biliary tree of the hamsters harbors H. pylori and Helicobacter-like bacteria. Accordingly, the association between O. viverrini and H. pylori may be an obligatory mutualism.

The Change in Biological Activities of Brown Rice and Germinated Brown Rice (품종별 현미 발아 전후의 생리활성물질 변화)

  • Kim, Dae-Jung;Oh, Sea-Kwan;Yoon, Mi-Ra;Chun, A-Reum;Choi, Im-Soo;Lee, Dong-Hyun;Lee, Jun-Soo;Yu, Kwang-Won;Kim, Yeon-Kyu
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.40 no.6
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    • pp.781-789
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    • 2011
  • We studied the biological activities, including antioxidant compounds, antioxidant activities, anti-proliferative activities, and immunological activities of brown rice and germinated brown rice. We examined the DPPH, ABTS radical scavenging activity, and reducing power of 70% ethanol extracts from some cultivars of brown rice and germinated brown rice. The total polyphenol, total flavonoid, and ${\gamma}$-oryzanol contents of the extracts were measured with spectrophotometric methods. The Hongjinjubeyo brown rice and germinated brown rice extracts showed markedly higher antioxidative activity than those of 70% ethanol extracts from other cultivars. The 70% ethanol extracts from brown rice and germinated brown rice had the most effective anti-proliferative activity (cytotoxicity) against breast cancer cells (MCF-7) compared to colorectal cancer cells (HCT-116). A $500\;{\mu}g$/mL concentration of 70% Hongjinjubyeo ethanol extract had higher macrophage and mitogenic activities of immunological activity than other cultivars.

Bilolgical Activities of Conjugated Linoleic Acid (CLA) and Animal Products (Conjugated Linoleic Acid (CLA)의 생리활성과 축산식품)

  • Hur, S.J.;Lee, J.I.;Ha, Y.L.;Park, G.B.;Joo, S.T.
    • Journal of Animal Science and Technology
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    • v.44 no.4
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    • pp.427-442
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    • 2002
  • Conjugated linoleic acid(CLA) is a collective term for a group of positional (c8, c10; c9, c11; c10, c12, and c11, c13) and geometric(cis,cis; cis,trans; trans,cis; and trans,trans) isomers of octadecadienoic acid (linoleic acid) with conjugated double bond system. CLA has been shown to have a variety of biological effects. Major effects of CLA on health, such as anti-cancer, anti-oxidation, anti-atherosclerosis and improving immuno-responses, might be derived or partially derived from the alternated lipid metabolism after CLA feeding. Most of studies on the effect of CLA on fat metabolism are concentrated on rats, mice, pigs and other mammals. The CLA inhibited carcinogen-induced neoplasia in several animal models and inhibited the proliferation of human malignant melanoma, colorectal and breast cancer cells and CLA reduced the atherosclerosis. Several studies have determined the antioxidant property of CLA; however, the property still remains controversial. Some of the studies have shown that CLA acted as an antioxidant, whereas some other studies have demonstrated that CLA might be a prooxidant. Several studies suggested that CLA could reduce fat accumulation in mammals. CLA was suggested to promote muscle growth and reduce fat deposition in mouse, and improve feed efficiency in rats. CLA has been shown to inhibit the activity of stearoyl-CoA reductase. CLA also reduced the content of arachidonic acid. Since arachidonic acid, and eicosapentaenoic acid (EPA) and docosahexenoic acid (DHA) are synthesized by different pathways, reducing the synthesis of arachidonic acid may not mean reducing that of EPA and DHA. Many sutdies have been shown biological effects of CLA. Therefore, further research is needed to answer the following questions: 1) how to synthesize the new CLA by new methods, 2) why CLA has shown biological effects, 3) how to increase CLA effects in animal products.

MICROSATELLITE INSTABILITY AND p53 GENE MUTATION IN ORAL SQUAMOUS CELL CARCINOMA (구강편평상피세포암 조직에서의 Microsatellite 불안정성 및 p53 유전자 돌연변이 분석)

  • Choi, Tae-Ho;Chung, Woon-Bok;Hong, Su-Hyung;Kim, Jin-A;Na, Sun-Oung;Jang, Hyun-Jung;Sohn, Yoon-Kyung;Kim, Chin-Soo;Kim, Jung-Wan
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.26 no.4
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    • pp.337-344
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    • 2000
  • Germ-line mutations at DNA repair loci confer susceptibility to colon cancer in hereditary non-polypopsis colorectal cancer. Somatic loss of DNA mismatch repair gene has been reported in a large variety of other tumor types. Replication errors(RERs) judged by microsatellite instability(MSI) and its associated mutations have been recognized as an important mechanism in various tumor types. To investigate associations between MSI and oral squamous cell carcinoma, the frequency of MSI using 12 microsatellite markers were analyzed for the series of oral tumors. Of 17 tumors, 8 cases(47%) did not show instability at any of the 12 loci; 5(29%) showed instability at $2{\sim}3$ loci; and 4(24%) showed instability above 4 loci. The 4 cases showing widespread MSI did not differ from those without evidence of instability in terms of age at diagnosis, degree of differentiation, metastasis to lymph node, tumor location or the presence of mutations in the p53 tumor suppressor gene. DCC and D17S 796 were the most frequently detected in MSI analysis. There were no correlation between smoking and MSI frequency, instead, smoking was suggested to increase the mutation rate of p53 and development of oral carcinomas.

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Microsatellite Instability and Promoter Methylation of hMLH1 in Sporadic Gastric Carcinoma (산발성 위암에서 Microsatellite Instability 빈도와 hMLH1 촉진자부위 메칠화)

  • Kim Hee Cheol;Roh Sun Ae;Yook Jeong Hwan;Oh Sung Tae;Kim Byung Sik;Yu Chang Sik;Kim Jin Cheon
    • Journal of Gastric Cancer
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    • v.3 no.1
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    • pp.50-55
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    • 2003
  • Background: An aberrant function of the mismatch repair system has been reported to underlie carcinogenesis in several tumors, including colorectal and gastric carcinomas, and to induce the typical genotype of microsatellite instability (MSI). Purpose: We aimed to determine the frequency of MSI in early-onset sporadic gastric carcinoma and elucidate the role of promoter methylation in hMLH1 as the mechanism of MSI. Materials and Methods: Thirty-six early-onset sporadic gastric carcinomas were analyzed to determine the status of MSI and the frequency of methylation of the promoter region in hMLH1. MSI was determined using five markers recommended by NCI: MSI-H (high), MSI-L (low), and MSS (Microsatellite stable). Methylation specific PCR (MSP) and direct automated genomic sequencing analysis with DNA modified by sodium bisulfite have been performed to confirm promoter region methylation. All the data were analyzed regarding characteristics of molecular changes, and clinicopathologic variables. Results: The microsatellite status was determined as MSI-H in five cases ($13.8\%$), MSI-L in 13 cases ($36.1\%$), and MSS in 18 cases ($50.0\%$). hMLH1 was methylated in seven cases ($19.4\%$). In all cases of MSI-H, promoter of hMLH1 was methylated, and in two of the 13 cases of MSI-L, hMLH1 promoter methylation was identified. Methylation was not found in any cases of MSS. Promoter methylation in hMLH1 was significantly correlated with MSI status (P<0.001). We could not find any relationship between MSI and clinicopathologic parameters. Conclusion: These results suggest that an abnormal function of the mismatch repair system may be associated with gastric carcinogenesis in more than $10\%$ of early-onset gastric carcinomas and MSI appeared to be closely related to the promoter methylation in hMLH1.

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Pyrrole-Derivative of Chalcone, (E)-3-Phenyl-1-(2-Pyrrolyl)-2-Propenone, Inhibits Inflammatory Responses via Inhibition of Src, Syk, and TAK1 Kinase Activities

  • Yang, Sungjae;Kim, Yong;Jeong, Deok;Kim, Jun Ho;Kim, Sunggyu;Son, Young-Jin;Yoo, Byong Chul;Jeong, Eun Jeong;Kim, Tae Woong;Han Lee, In-Sook;Cho, Jae Youl
    • Biomolecules & Therapeutics
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    • v.24 no.6
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    • pp.595-603
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    • 2016
  • (E)-3-Phenyl-1-(2-pyrrolyl)-2-propenone (PPP) is a pyrrole derivative of chalcone, in which the B-ring of chalcone linked to ${\beta}$-carbon is replaced by pyrrole group. While pyrrole has been studied for possible Src inhibition activity, chalcone, especially the substituents on the B-ring, has shown pharmaceutical, anti-inflammatory, and anti-oxidant properties via inhibition of NF-${\kappa}B$ activity. Our study is aimed to investigate whether this novel synthetic compound retains or enhances the pharmaceutically beneficial activities from the both structures. For this purpose, inflammatory responses of lipopolysaccharide (LPS)-treated RAW264.7 cells were analyzed. Nitric oxide (NO) production, inducible NO synthase (iNOS) and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) mRNA expression, and the intracellular inflammatory signaling cascade were measured. Interestingly, PPP strongly inhibited NO release in a dose-dependent manner. To further investigate this anti-inflammatory activity, we identified molecular pathways by immunoblot analyses of nuclear fractions and whole cell lysates prepared from LPS-stimulated RAW264.7 cells with or without PPP pretreatment. The nuclear levels of p50, c-Jun, and c-Fos were significantly inhibited when cells were exposed to PPP. Moreover, according to the luciferase reporter gene assay after cotransfection with either TRIF or MyD88 in HEK293 cells, NF-${\kappa}B$-mediated luciferase activity dose-dependently diminished. Additionally, it was confirmed that PPP dampens the upstream signaling cascade of NF-${\kappa}B$ and AP-1 activation. Thus, PPP inhibited Syk, Src, and TAK1 activities induced by LPS or induced by overexpression of these genes. Therefore, our results suggest that PPP displays anti-inflammatory activity via inhibition of Syk, Src, and TAK1 activity, which may be developed as a novel anti-inflammatory drug.