• Journal of the Korean Society of Food Science and Nutrition
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• v.33 no.1
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• pp.1-6
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• 2004

$\beta$-Sitosterol is the major phytosterol in higher plants, including fruits and vegetables. The molecule has been shown to have the potential for prevention and therapy for human cancer. We investigated the effects of $\beta$-sitosterol on the cell proliferation of HCT116 human colon cancer cells in order to understand its anti-proliferative mechanism. $\beta$-Sitosterol treatment resulted in the inhibition of cell proliferation in a concentration-dependent manner. The anti-proliferative effect of HCT116 cells by $\beta$-sitosterol was associated with formation of apoptotic bodies and degradation of $\beta$-catenin protein. In addition, $\beta$-sitosterol-treatment induced a marked accumulation of tumor suppressor p53 and a concomitant induction of cyclin-dependent kinase (Cdk) inhibitor p21 without alteration in the levels of cyclins and Cdks. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of $\beta$-sitosterol.

• Biomedical Science Letters
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• v.12 no.3
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• pp.153-160
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• 2006

Human colon cancer is the second most fatal disease among a variety of cancers to cause cancer death in U.S.A. and its incidence rate is currently increased in Korea. Recently, many studies have been being progressed on the efficacy of diverse combination treatments. But results of these studies in vitro were not similar those in vivo. This study compared the anticancer reactions between each use of arsenic trioxide and taxol against human colon cancer HT-29 cell line and combined use of two drugs. And these results compared with the results of HT-29 spheroid cells having similar characteristics to the solid tumor in vivo. The spheroid of HT-29 cells was formed by using a multicellular spheroid system and the result was observed through electron microscopy. In vitro cytotoxicity of each use of arsenic trioxide and taxol was evaluated in HT-29 monolayer cells. The $IC_{50}$ value for arsenic trioxide was to be $33{\mu}M$ and taxol was to be 18nM. The result treated with the combination of taxol and arsenic trioxide decreased the cytotoxicity on the HT-29 monolayer cells. The spheroid cells represented higher resistance against drugs than the monolayer cells. I demonstrated DNA fragmentation after incubation with concentrations more than $10{\mu}M$ arsenic trioxide and 100nM taxol for 48h, on the monolayer cells. But the results of HT-29 cell line treated with the combination of taxol and arsenic trioxide was the same as the outcome of control samples that were not treated with any drug. And I don't demonstrated DNA fragmentation on the spheroid cells. These results suggest that apoptosis was not induced in the use of the combination can be thought as that arsenic trioxide might work as an antagonist to inhibit a taxol mechanism to induce apoptosis. And the spheroid cells represented higher resistance against drugs than the monolayer cells.

• Molecules and Cells
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• v.37 no.12
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• pp.899-906
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• 2014

Prostaglandin $E_2$ ($PGE_2$) promotes tumor-persistent inflammation, frequently resulting in cancer. Curcumin is a diphenolic turmeric that inhibits carcinogenesis and induces apoptosis. $PGE_2$ inhibits curcumin-induced apoptosis; however, the underlying inhibitory mechanisms in colon cancer cells remain unknown. The aim of the present study is to investigate the survival role of $PGE_2$ and whether addition of exogenous $PGE_2$ affects curcumininduced cell death. HCT-15 cells were treated with curcumin and $PGE_2$, and protein expression levels were investigated via Western blot. Reactive oxygen species (ROS) generation, lipid peroxidation, and intracellular glutathione (GSH) levels were confirmed using specific dyes. The nuclear factor-kappa B ($NF-{\kappa}B$) DNA-binding was measured by electrophoretic mobility shift assay (EMSA). $PGE_2$ inhibited curcumin-induced apoptosis by suppressing oxidative stress and degradation of PARP and lamin B. However, exposure of cells to the EP2 receptor antagonist, AH6809, and the PKA inhibitor, H89, before treatment with $PGE_2$ or curcumin abolished the protective effect of $PGE_2$ and enhanced curcumin-induced cell death. $PGE_2$ activates PKA, which is required for cAMP-mediated transcriptional activation of CREB. $PGE_2$ also activated the Ras/Raf/Erk pathway, and pretreatment with PD98059 abolished the protective effect of $PGE_2$. Furthermore, curcumin treatment greatly reduced phosphorylation of CREB, followed by a concomitant reduction of $NF-{\kappa}B$ (p50 and p65) subunit activation. $PGE_2$ markedly activated nuclear translocation of $NF-{\kappa}B$. EMSA confirmed the DNA-binding activities of $NF-{\kappa}B$ subunits. These results suggest that inhibition of curcumin-induced apoptosis by $PGE_2$ through activation of PKA, Ras, and $NF-{\kappa}B$ signaling pathways may provide a molecular basis for the reversal of curcumin-induced colon carcinoma cell death.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3757-3761
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• 2012

Objective: Crocin has been proposed as a promising candidate for cancer chemoprevention. The purpose of this investigation was to investigate the chemopreventive action and the possible mechanisms of crocin against human colon cancer cells in vitro. Methods: Cell proliferation was examined using MTT assay and the cell cycle distribution fractions were analyzed using fow cytometric analysis after propidium iodide staining. Apoptosis was detected using theTUNEL Apoptosis Detection Kit with laser scanning confocal microscope. DNA damage was assessed using the alkaline single-cell gel electrophoresis assay, while expression levels of p53, cdk2, cyclinA and P21 were examined by Western blot analysis. Results: Treatment of SW480 cells with crocetin (0.2, 0.4, 0.8 mmol/L) for 48 h signifcantly inhibited their proliferation in a concentration-dependent manner. Crocetin (0.8 mmol/L) signifcantly induced cell cycle arrest through p53-independent mechanisms accompanied by P21 induction. Crocetin (0.8 mmol/L) caused cytotoxicity in the SW480 cells by enhancing apoptosis and decreasing DNA repair capacity in a time-dependent manner. Conclusions: This report provides evidence that crocetin is a potential anticancer agent, which may be used as a chemotherapeutic drug.

• Asian-Australasian Journal of Animal Sciences
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• v.25 no.11
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• pp.1617-1626
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• 2012

The objective of this study was to evaluate the effects of adding essential oils to the diet of weaned pigs on performance, nutrient utilization, immune response and intestinal health. A total of 96 weaning pigs ($8.37{\pm}1.58$ kg) were allotted to one of three dietary treatments. The treatments consisted of an unsupplemented basal diet (negative control, NC) or similar diets supplemented with 0.01% of an essential oil product which contained 18% thymol and cinnamaldehyde (EOD) as well as a diet supplemented with 0.19% of an antibiotic mixture which provided 150 ppm chlortetracycline, 80 ppm colistin sulfate and 50 ppm kitasamycin (positive control, PC). Each treatment was provided to eight pens of pigs with four pigs per pen. Over the entire 35 d experiment, ADG and fecal score were improved (p<0.05) for pigs fed the PC and EOD compared with the NC. Dry matter and crude protein digestibility as well as lymphocyte proliferation for pigs fed the PC and EOD diets were increased significantly compared with NC (p<0.05). IGF-I levels in plasma were significantly increased (p<0.05) in pigs fed the PC diet compared with pigs fed the NC diet. Interleukin-6 concentration was lower (p<0.05) and the tumor necrosis factor-${\alpha}$ level was higher (p<0.05) in the plasma of pigs fed the EOD diet than the NC diet. Plasma total antioxidant capacity level increased (p<0.05) in pigs fed the EOD diet compared with pigs fed the NC. Villus height to crypt depth ratio in the jejunum was greater (p<0.05) in pigs fed the PC and EOD diets than the NC. The numbers of E. coli in the cecum, colon and rectum were reduced (p<0.05) in pigs fed the PC and EOD diets compared with the control. In the colon, the ratio of Lactobacilli to E. coli was increased (p<0.05) in pigs fed the EOD diet compared with NC diet. Total aerobe numbers in the rectum were decreased (p<0.05) in pigs fed the PC and EOD diets compared with the control. Collectively, these results indicate that blends of essential oils could be a candidate for use as an alternative to traditional antibiotics in weaning pig diets.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.13
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• pp.5337-5341
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• 2014

Background: The standard therapy for stage I rectum cancer is surgical resection. Currently, there is no strong evidence to suggest that any type of adjuvant therapy is beneficial. The risks of local relapse and distant metastasis are higher in rectal tumors. Therefore, while there is no clearly defined absolute indication for adjuvant therapy in lymph node negative colon cancers, rectum tumors that are T3N0 and higher require adjuvant treatment. Due to the more aggressive nature of rectal cancers, we explored the clinical and pathologic factors that could predict the risk of relapse in Stage I (T1-T2) disease and whether there was any progression-free survival benefit to adjuvant therapy. Materials and Methods: This multicenter study was carried out by the Anatolian Society of Medical Oncology. A total of 178 patients with rectal cancers who underwent curative surgery between January 1994 and August 2012 in 13 centers were included in the study. Patient demographics, including survival data and tumor characteristics were obtained from medical charts. Results: The median age was 58 years (range 26-85 years). Most tumors were well or moderately differentiated. For adjuvant treatment, 13 patients (7.3%) received radiotherapy alone, 12 patients (6.7%) received chemotherapy alone and 15 patients (8.4%) were given chemoradiotherapy. Median follow up was 29 months (3-225 months). Some 42 patients (23.6%) had relapse during follow up; 30 with local recurrence (71.4%) whereas 12 (28.6%) were distant metastases. Among the patients, 5-year DFS was 64% and OS was 82%. Mucinous histology and receiving adjuvant therapy were found to have statistically insignificant correlations with relapse and survival. Conclusions: In our retrospective analysis, approximately one quarter of patients exhibited either local or systemic relapse. The rates of relapse were slightly higher in the patients who had no adjuvant therapy. There may thus be a role for adjuvant therapy in high-risk stage I rectal tumors.

• Journal of Chest Surgery
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• v.16 no.2
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• pp.231-242
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• 1983

A clinical study was performed on 75 cases of the esophageal cancer and benign esophageal diseases experienced at Department of thoracic & cardiovascular surgery, School of Medicine, Keimyung University during 3 year period from 1978 to 1982. Of 75 cases of the surgical esophageal diseases, there were 35 patients of the esophageal cancer. 17 patients of benign esophageal stenosis, 10 patients of esophageal perforation, 4 patients of diverticulum. 3 patients of achalasia, 2 patients of congenital T-E fistula, one of upper esophageal web, one of esophageal foreign body, one of leiomyoma and patient of hemangioma. First, esophageal carcinoma was more frequent in men than in women by a ratio of five to one, and the peak incidence occurred in the 5th to 6th decade. Dysphagia was the most common symptom in 88.6 percent of our cases. The tumor was located mostly in the middle & the lower one third [91.4%]. The histological diagnosis was made in 35 cases. The squamous cell carcinoma was the most common [82.9%] and the rest was the adenocarcinoma in the lower one third [17.1%]. Thirty-five cases were operated and resection was feasible in the twenty-five patients [71.4%] with 2 cases of hospital mortality [5.7%]. All but two of the esophageal stenosis were caused by corrosive esophagitis and ages ranged from 7 to 70 years with average age of 32 years. Corrective operations were performed on 17 patients of esophageal stenosis of whom 12 patients had esophagocologastrostomy, 3 patients esophagogastrostomy and in non-corrosive esophageal stenosis one case and esophagoplasty and another case had release of external compression. There was one complication of stenosis of the esophageal perforation were traumatic in five cases, empyema in three cases, caustics in one case and postemetic in one case. 10 patients of the esophageal perforation underwent operation: primary closure in 5 cases, two staged colon interposition in 2, esophagogastrostomy in 1 and closed thoracotomy in 2 cases There were 2 complications of leakage of anastomosis sites in postoperative period. 4 patients of traction type of diverticulum underwent diverticulectomy & 3 patients of achalasia underwent modified Heller`s operation. 2 patients of congenital esophageal atresia had distal tracheoesophageal fistula & underwent one staged operation with the results of one death caused by pneumonia. Upper esophageal web had divulsion through the esophagoscope and foreign body in upper esophagus was removed through cervical esophagotomy. One case of leiomyoma in esophagus had esophagectomy and reconstruction with right colon. And one case of hemangioma in esophagus had esophagectomy & esophagogastrostomy.

• Gut and Liver
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• v.12 no.6
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• pp.664-673
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• 2018

Background/Aims: Regulatory dendritic cells (rDCs), which can be induced by mesenchymal stem cells (MSCs), play an important role in inducing and maintaining homeostasis of regulatory T cells and exhibit anti-inflammatory functions. In this study, we investigated whether MSCs could differentiate DCs into rDCs and compared the therapeutic effects of rDCs and MSCs on dextran sodium sulfate (DSS)-induced chronic colitis mice. Methods: Immature DCs (imDCs) and lipopolysaccharide (LPS)-treated mature DCs (mDCs) were co-cultured with MSCs for 48 hours, and then the profiles of surface markers and cytokines and regulatory roles of these DCs for primary splenocytes were analyzed. In addition, the therapeutic effects of MSCs and DCs co-cultured with MSCs were compared in chronic colitis mice. Results: After co-culture of imDCs (MSC-DCs) or LPS-treated mDCs (LPS+MSC-DCs) with MSCs, the expression of CD11c, CD80, CD86, interleukin 6 (IL-6), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), and interferon-${\gamma}$ (IFN-${\gamma}$), was decreased, but that of CD11b, IL-10, and transforming growth factor-${\beta}$ (TGF-${\beta}$) was increased. Furthermore, MSC-DCs and LPS+MSC-DCs induced the expression of CD4, CD25, and Foxp3 in primary splenocytes isolated from mice. In DSS-induced colitis mice, MSCs and MSC-DCs increased colon length, body weight, and survival rate and induced histological improvement. Moreover, in the colon tissues, the expression of IL-6, TNF-${\alpha}$, and IFN-${\gamma}$ decreased, but that of IL-10, TGF-${\beta}$, and Foxp3 increased in the MSC- and MSC-DC-injected groups. Conclusions: Our data suggest that MSCs differentiate DCs into rDCs, which ameliorate chronic colitis. Thus, rDCs stimulated by MSCs may be therapeutically useful for the treatment of chronic inflammatory diseases.

• Journal of Life Science
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• v.27 no.11
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• pp.1245-1255
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• 2017

Most cancer cells produce ATP predominantly through glycolysis instead of through mitochondrial oxidative phosphorylation, even in the presence of oxygen. The phenomenon is termed the Warburg effect, or the glycolytic switch, and it is thought to increase the availability of biosynthetic precursors for cell proliferation. EMTs have critical roles in the initiation of the invasion and metastasis of cancer cells. The glycolytic switch and EMT are important for tumor development and progression; however, their correlation with tumor progression is largely unknown. The Snail transcription factor is a major factor involved in EMT. The Snail expression is regulated by distal-less homeobox 2 (Dlx-2), a homeodomain transcription factor that is involved in embryonic and tumor development. The Dlx-2/Snail cascade is involved in Wnt-induced EMTs and the glycolytic switch. This study showed that in response to Wnt signaling, the Dlx-2/Snail cascade induces the expression of PFKFB2, which is a glycolytic enzyme that synthesizes and degrades fructose 2, 6-bisphosphate (F2,6BP). It also showed that PFKFB2 shRNA prevents Wnt-induced EMTs in the breast-tumor cell line MCF-7. The prevention indicated that glycolysis is linked to Wnt-induced EMT. Additionally, this study showed PFKFB2 shRNA suppresses in vivo tumor metastasis and growth. Finally, it showed the PFKFB2 expression is higher in breast, colon and ovarian cancer tissues than in matched normal tissues regardless of the cancers' stages. The results demonstrated that PFKFB2 is an important regulator of EMTs and metastases induced by the Wnt, Dlx-2 and Snail factors.

• The Korean Journal of Nuclear Medicine Technology
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• v.14 no.2
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• pp.145-149
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• 2010

Purpose: Recently, $^{18}F$-FDG Fusion PET which has a high sensitivity for diagnosing cancer is being used for purpose of health examination. This study is to demonstrate that $^{18}F$-FDG fusion PET study is useful for diagnosing an early stage cancer. Materials and Methods: This research has been conducted with 2790 patients visited Seoul National University Hospital Healthcare System (SNUHHS) for $^{18}F$-FDG fusion PET study for a health examination from February, 2004 to December 2008. PET/CT images were acquired from skull base to femur after 1 hour from injecting $^{18}F$-FDG 0.14 mCi/kg to the patients. GEMINI GS (Philips, Netherlands) was used for scanning. Results: From February 2004 to December 2008, $^{18}F$-FDG Fusion PET study was performed for 99,009 patients among all patients who visited SNUHHS and 2,790 patients was performed. Diagnostic rate for malignant cancer was 0.95% for the patients who were not examined by $^{18}F$-FDG Fusion PET study. 1.94% was for the patients who were. The rate of malignant tumor was showed 10% and benign tumor was 90% among 542 patients who showed abnormality in the PET/CT images. Types and rates of malignant tumor showed thyroid cancer: 31.5%, lung cancer: 14.8%, stomach cancer: 9.3%, rectum cancer: 3.7%, breast cancer: 3.7%, metastasis cancer: 16.7%. Nonspecific lymph node in the mediastinum, physiologic uptake in the colon, diffuse mild hypermetabolism in bilateral thyroid gland were shown as a benign tumor. Conclusion: The diagnostic rate of malignant tumor with $^{18}F$-FDG Fusion PET for a purpose of health examination was relatively higher than general medical examination. Consequently, it is superior and useful for applying $^{18}F$-FDG Fusion PET study for health examination.